Abstracts, 21st PANLAR Meeting: Quito, Ecuador, April 2019

CONCURRENT ORAL SESSIONS

212

TYPE II BUT NOT TYPE I IFN SIGNIFIES CLINICAL RESPONSE TO USTEKINUMAB IN PATIENTS WITH SLE

Jarrat Jordan¹, Kristen Sweet¹, Matteo Cesaroni¹, Loqmane Seridi¹, Federico Zazzetti³, Peter Lipsky², Shawn Rose¹, Frédéric Baribaud¹, Matthew Loza¹, and Kim Campbell¹. ¹Janssen Research & Development, LLC, Spring House, United States, ²AMPEL BioSolutions, LLC, Charlottesville, United States, ³Janssen-Cilag, Buenos-Aires, Argentina.

Objectives: Treatment with ustekinumab (UST), an anti-IL-12/23, p40-neutralizing monoclonal antibody, improved global and organ-specific measures of disease activity in a randomized, placebo (PBO)-controlled trial of patients with active SLE (NCT02349061) ¹. Type I interferon (IFN-I) and type II IFN (IFN-y) are elevated in a subset of SLE patients. Although targeting IFN-I (anifrolumab) has demonstrated inconsistent efficacy and a preliminary study with anti-IFN-y mAb (AMG811) failed to establish benefit^2,3 we sought to determine if UST affects either pathway and if those effects correlated with a positive SRI-4 response at wk24.

Methods: A phase-2, PBO-controlled study enrolled 102 adults with seropositive SLE (SLICC criteria) and active disease (baseline SLEDAI score ≥6 and ≥1 BILAG A and/or ≥2 BILAG B scores) despite standard-of-care therapy¹. Gene expression analysis using a 21 gene IFN-I gene signature (IGS)⁴ or IFN-y signature⁵ was performed by microarray analysis using whole blood PAXgene RNA samples. Serum IFN-y and IFN-α levels were assessed using MSD (IFN-y) and Quanterix (IFN-α).

Results: Serum IFN-y and IFN-α and the IGS were elevated at baseline in SLE compared to healthy controls (p<0.0001). IGS was increased in approximately 67% of the SLE patients at baseline. No decrease was observed with IFN-α protein or IGS levels after treatment with either UST or PBO. Whereas the proportion of patients achieving an SRI-4 response at wk24 was numerically greater in the IGS low patients (81.8% UST vs. 54.5% PBO) versus IGS high (48.6% UST vs. 20% PBO), the magnitude of the treatment effect (UST vs. PBO) was similar in both subsets (IGS low effect size= 27.3% vs. IGS high effect size = 28.6%). Despite similar baseline levels, UST-treated patients achieving an SRI-4 response at wk24 exhibited a significant decrease in IFN-y protein versus non-responders (p<0.05) at 4 and 8 wks and IFN-y gene signature at 4 wks (p<0.0001) and 24 wks (p<0.05) post-dosing.

Conclusions: In this SLE trial population which had significant upregulation of IFN-I at baseline, clinical response to UST was not associated with IFN-I reduction. In contrast, a significant decrease in IFN-y protein and gene signature was associated with UST response. These findings suggest that a broad population of SLE patients may respond to UST regardless of baseline IFN-I status. Moreover, UST may have affected TH1 responses in SLE since IFN-y levels decreased following treatment.

References:

¹VanVollenhoven RF. Lancet.2018:392:1330.

²Furie R. ArthritisRheumatol.2017;69:376.

³Boedigheimer M.J. LupusSciMed.2017;4: e000226.

⁴Yao Y. HumanGenomicsProteomics.2009; doi:10.4061/2009/374312.

⁵Welcher AA. Arthritis&Rheumatol.2015;67:2713.

23

IMMUNOGLOBULIN A VASCULITIS: COMPARISON BETWEEN PEDIATRIC AND ADULT POPULATIONS

Martin Brom¹, Ignacio Javier Gandino¹, Marina Scolnik¹, Valeria Scaglioni¹, Maria Britos¹, Carmen De Cunto¹, and Enrique Roberto Soriano¹. ¹Hospital Italiano De Buenos Aires, Ciudad Autonoma De Buenos Aires, Argentina.

Objectives: To describe the clinical features, laboratory findings, treatment used and prognosis of Immunoglobulin A (IgA) Vasculitis (formerly Schönlein-Henoch purpura) in both pediatric and adult patients, and evaluate the differences between these groups, especially regarding renal outcome.

Methods: We performed a medical records review study on all patients with IgA vasculitis that were followed at a university hospital between 01/01/2000 and 05/01/2018.

We included all patients that fulfilled EULAR/PRINTO/PRES 2010 criteria, and collected and analyzed demographic, clinical, treatment and histopathologic information available on their electronic medical records.

We considered as pediatric patients those who were under 20 years when they were diagnosed.

Results: One-hundred eighteen patients were included, being 107 pediatric and 11 adults.

Clinical manifestations were similar in both groups except for kidney involvement that was more frequent in adults (36% vs 73%, p=0.02) while arthralgias (53% vs 18%, p=0.03) and scalp edema (42% vs 9%, p=0.03) were more frequent in children. Kidney biopsy was performed in 5/8 of the adult affected patients, with confirmatory histopathology for IgA vasculitis in all of them.

Since adults showed more severe clinical manifestations, significantly more corticosteroids and immunosuppressants were used in this group. As a consequence of the disease, 2 of the affected adults suffered from chronic kidney disease; one of them required kidney transplantation. No pediatric patient presented chronic kidney disease. Finally, 2 deaths occurred, both in the adult group, but only one was related to the disease.

Conclusions: Adult patients with IgA vasculitis suffered a more aggressive disease, with more renal involvement and required more intense treatment.

24

AUTOIMMUNE INTERSTITIAL LUNG DISEASE. CHARACTERISTICS AND TREATMENT STRATEGIES OF A LATIN-AMERICAN COHORT. EPIMAR GROUP

Florencia Vivero¹, Federico Campins¹, Silvia Babini¹, Pablo Malfante¹, Diana Lancellotti¹, Esteban Gándara¹, Juan Ignacio Enghelmayer², Victoria Basso¹, Javier Sebastiani¹, Adrián Gaser³, Silvia Quadrelli⁴, Patricia Aruj⁵, Carolina Isnardi⁶, Mónica Sacnun⁷, Norma Naval⁸, Viviana Moyano⁹, Soledad Altube¹⁰, Magdalena Romiti¹, Mariana Lagrutta¹¹, Brenda Varela¹², Javier Abdala¹³, Paulin Francisco¹⁴, Gabriela Tabaj¹⁵, María Laura Alberti¹⁴, Santiago Auteri¹⁶, Joaquín Maritano¹⁷, Marcela Usandivaras¹⁸, Virginia Larivey¹⁹, Julio Fuertes Avila²⁰, Germán Arce²¹, Ramiro Gomez², Lilian Capone²², Luciana Molinari²³, Matias Castro¹⁷, Victoria Avalos²⁴, Alejandro Albiero²⁵, Hernan Basilo Vigil²⁶, Adriana Robles²⁷, Franco Pacello²⁸, Victoria Collado⁵, Guillermo Pons Estel²⁹, Gabriela Manonelles³⁰, Fabián Caro⁴, Maria Otaola⁶, and Marina Oliver¹. ¹Hospital Privado De Comunidad, Mar Del Plata, Argentina, ²Hospital de Clínicas, Buenos Aires, Argentina, ³Instituto Diagnóstico Médico, Buenos Aires, Argentina, ⁴Sanatorio Güemes, Buenos Aires, Argentina, ⁵Instituto de investigaciones clínicas Dr. Lanari, Buenos Aires, Argentina, ⁶Instituto de rehabilitación psicofísica, Buenos Aires, Argentina, ⁷Hospital Provincial, Rosario, Argentina, ⁸Hospital Ángel Padilla, San Miguel de Tucumán, Argentina, ⁹Hospital Italiano, Córdoba, Argentina, ¹⁰Hospital Municipal, Chivilcoy, Argentina, ¹¹Hospital Centenario, Rosario, Argentina, ¹²Hospital Alemán, Buenos Aires, Argentina, ¹³Hospital Central, Mendoza, Argentina, ¹⁴Hospital Maria Ferrer, Buenos Aires, Argentina, ¹⁵Hospital Cetrángolo, Buenos Aires, Argentina, ¹⁶Sanatorio de la Mujer, Rosario, Argentina, ¹⁷Hospital Italiano, Buenos Aires, Argentina, ¹⁸Sanatorio 9 de julio, San Miguel de Tucumán, Argentina, ¹⁹Hospital Sayago, Santa Fe, Argentina, ²⁰Clinica de artritis temprana, Cali, Colombia, ²¹Grupo Gamma, Rosario, Argentina, ²²Instituto Vaccarezza, Buenos Aires, Argentina, ²³Clinica Roca, General Roca, Argentina, ²⁴Hospital Churruca, Buenos Aires, Argentina, ²⁵Sanatorio Allende, Córdoba, Argentina, ²⁶Hospital Tornú, Buenos Aires, Argentina, ²⁷Hospital San Bernardo, Salta, Argentina, ²⁸Unidad de Enf Autoinmunes, Paysandú, Uruguay, ²⁹Sanatorio Parque, Rosario, Argentina, ³⁰Instituto Aike, Rio Gallegos, Argentina.

Objectives: The prevalence, clinical and radiological features along with the natural course of lung diseases (ILD) with autoimmune phenomena (Ai-ILD) as a whole are not entirely known as most of the studies available are limited to specific subsets of patients such as those with ILDs associated with well-defined connective tissue diseases (ILD-CTD), interstitial pneumonia with autoimmune features (IPAF) or ILD associated with anti-neutrophil cytoplasmatic antibodies (ILD-ANCA).

The aim of this study was to evaluate the clinical, radiological, functional, serological and therapeutic features of all patients diagnosed with Ai-ILD in a Latin America cohort.

Methods: We conducted a multicenter cohort study in hospitals from Argentina, Colombia, and Uruguay between January 2015 and April 2018. All the facilities selected to participate provided specialized care to patients with ILD by a multi-disciplinary team. Ai-ILD was defined as the presence of lung images suggestive of ILD in a chest high-resolution computed tomography (HRCT) associated with: 1) the presence of CTD defined according to international classification guidelines, or 2) the presence of IPAF according to the 2015 ERS/ATS criteria, or 3) the presence of ANCA by indirect immunofluorescence ELISA confirmed. All CT scans were evaluated by a specialist in radiology focused in chest disease, who was blinded to the participant’s medical history or suspected diagnosis. The following variables were collected: demographic features, co-morbidities, smoking, date of Ai-ILD diagnosis, serological data, ILD tomographic pattern, pulmonary function test (PFT), therapeutic schemes.

Results: During the study period 381 participants were enrolled. Female participants predominated (74%) with an average age of 58 years (SD 16). The most frequent diagnosis was ILD-CTD (85.3%) followed by IPAF (9.5%) and ILD-ANCA 3.5%. Regarding ILD-CTD, the most frequent condition was rheumatoid arthritis (RA) 31%, followed by systemic sclerosis (SSc) 28.6%. More frequent anti-bodies were anti-nuclear antibody (ANAs) (60,6%), rheumatoid factor (RF) (38%), anti-cyclic citrullinated peptide (CCP) (24%). Average baseline % forced vital capacity was 70% (SD 18.3). Forty-four percent of the participants presented severe restriction at the time of diagnosis, while 50.28% had mild restriction. The most frequent tomographic pattern was non-specific interstitial pneumonia (NSIP) accounting for 51.08% (95% CI 45.65 - 56.49) of all cases followed by usual interstitial pneumonia (UIP) with 21.36%. The most commonly used therapeutic regimen was steroids plus cyclophosphamide 30.1%, followed by azathioprine (20.3%). Corticosteroid pulses were used in (39.8%) of the participants.

Conclusions: Rheumatologists play an essential role in the selection of specific therapeutic strategies for the management of patients affected by Ai-ILD. EPIMAR is an important first step to better understand the characteristics of these patients. To the best of our knowledge, this is the first Latin American multicenter cohort study comprising facilities with experience in ILD management. Longitudinal studies are needed to better understand the outcome of patients treated with Ai-ILD

73

EXPRESSION OF MIR-3148 AND ITS CORRELATION WITH MRNA AND COPY NUMBER VARIATION OF THE TLR7 GENE IN MAYAN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS FROM MEXICO

Guillermo Valencia Pacheco¹, Yumi E Nakazawa Ueji¹, Darig Camara Cruz¹, Gerardo J Perez Mendoza¹, Angelica V Angulo Ramirez², and Ricardo F López Villanueva³. ¹Laboratorio de Hematología. Centro de Investigaciones Regionales Dr. Hideyo Noguchi, de la Universidad Autonoma De Yucatan, Merida, Mexico, ²Hospital Regional de Alta Especialidad de la Peninsula de Yucatan, Merida, México, ³Hospital General Regional (ISSSTE), Servicio de Salud de Yucatán, Merida, Mexico.

Objectives: Genetic factors such as copy number variation (CNV) of genes involved in the immune response, and epigenetic factors such as microRNA (miR), have been associated with the development of SLE. TLR7 is a innate immunity receptor, which has been implicated in the pathology of SLE.

Our objective was to correlate the expression of miR-3148 with the levels of mRNA and CNV of the TLR7 gene in Mayan women with SLE.

Methods: We studied 100 women diagnosed with SLE and 100 healthy women as a control group, all of Mayan origin. The expression of miR-3148, CNV, and mRNA of the TLR7 gene was determined by real-time PCR (Q-PCR) using TaqMan probes. The estimation of CNV, mRNA and miR was made by calculating 2-ΔΔCt.The association of CNV of the TLR7 gene with the disease was determined by the Odds Ratio (OR) with a confidence interval of 95%, and the results were contrasted by the χ square test. Correlation analysis was performed between CNV, mRNA, and miR-3148, using the Pearson test, considering as significant a value of p <0.05.

Results: We found that 17% of the patients presented more than two copies of the TLR7 gene, with respect to the controls. The analysis of association of CNV with the disease shows that the risk of developing SLE is almost 41 times higher in people with more than two copies with respect to those of two copies of the TLR7 gene (OR = 40.96, 95% CI 2.42 - 692.31, p=0.0001). Significant difference was observed in the CNV and mRNA expression of the TLR7 gene between patients and controls (p <0.0001). A correlation was found between CNV and TLR7 mRNA (r=0.4080, p=0.0016) and between miR-3148 and mRNA (r=0.5950, p=0.0002) in the patients; however, no correlation was observed between the CNV and expression of miR-3148.

Conclusions: These results indicate that Mayan women with more than two copies of TLR7 gene are more susceptible to developing SLE. The correlation between mRNA and CNV in patients supports the participation of the TLR7 gene in the disease. No correlation was observed between the CNV and miR-3148 in the patients indicating that TLR7 gene does not influence the expression of miR-3148.It is necessary to analyze other miR that regulate the expression of TLR7 gene. These data suggest that genetic and epigenetic variables may be risk markers to develop the disease in the Mayan population

157

FREQUENCY OF NEONATAL LUPUS IN REFERENCE CENTERS IN THE MANAGEMENT OF PREGNANCY AND AUTOIMMUNE DISEASES

Carla Maldini¹, Cintia Otaduy¹, Florencia Beatriz Mollerach², Marina Scolnik², Belén Maria Virasoro³, Cecilia Pisoni³, Mercedes Croce⁴, María Hu⁴, Fabiola Natalia Camargo Serrudo⁵, Diana Dubinsky⁵, María de la Paz Leon⁶, Veronica Bellomio⁶, Daniela Flores Rengifo⁷, Sabrina Porta⁷, Fernanda Guzzanti⁸, Emma E Civit⁸, Ana Bertoli⁹, María José Lopez Perez⁹, Maximiliano Machado Escobar¹⁰, Veronica Savio¹¹, Alejandra Babini¹¹, Cecilia Alvarez¹², Verónica Saurit¹², Rosa Serrano Morales¹³, Cruz Lascano¹⁴, María Constanza Danielsen¹⁵, Mayra Etcheverry¹⁶, Adrian Estevez¹⁶, Marina Werner¹⁷, Laura Onetti¹⁷, Paula Alba¹, and Carla Gobbi¹⁸. ¹Cátedra de Semiología UHMI 3 Hospital Córdoba FCM Universidad Nacional de Córdoba, Cordoba, Argentina, ²Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina, ³Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno (CEMIC), Ciudad Autónoma de Buenos Aires, Argentina, ⁴Hospital Penna, Ciudad Autónoma de Buenos Aires, Argentina, ⁵Sanatorio Guemes, Ciudad Autónoma de Buenos Aires, Argentina, ⁶Hospital Padilla, San Miguel de Tucumán, Argentina, ⁷Hospital J. M. Ramos Mejía, Ciudad Autónoma de Buenos Aires, Argentina, ⁸Hospital El Carmen, Mendoza, Argentina, ⁹Clínica Universitaria Reina Fabiola. Universidad Católica de Córdoba, Córdoba, Argentina, ¹⁰Instituto de Maternidad y Ginecologia Nuestra Sra de las Mercedes, San Miguel de Tucumán, Argentina, ¹¹Hospital Italiano, Córdoba, Argentina, ¹²Servicio de Reumatología, Hospital Privado Universitario de Córdoba, Córdoba, Argentina, ¹³Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR)/Maternidad Oroño, Rosario, Argentina, ¹⁴Hospital San Roque, San Salvador de Jujuy, Argentina, ¹⁵Clínica del Pilar, Santiago del Estero, Argentina, ¹⁶Hospital de Alta Complejidad El Cruce, Buenos Aires, Argentina, ¹⁷Hospital Nacional de Clínicas, Córdoba, Argentina, ¹⁸Cátedra de Clínica Médica I, Hospital Córdoba FCM Universidad Nacional de Córdoba, Córdoba, Argentina.

Objectives: Neonatal lupus (NL) is a disease in children of mothers who have specific anti-Ro/La IgG autoantibodies by passive transplacental transfer. NL is characterized by skin and cardiac involvement, as well as cytopenias, hepatic or neurological manifestations. NL can be diagnosed intra-uterus or in the neonatal period, being self-limiting in several months or be irreversible. Objetives: to estimate the frequency of NL in children of mothers with anti-Ro/La in reference centers in the management of pregnancy and autoimmune diseases in Argentina, and to describe maternal and children features.

Methods: A descriptive multicenter study was conducted in reference centers in the management of autoimmune diseases and pregnancy in Argentina. Inclusion criteria were the presence of positive maternal serology anti-Ro/La and at least one pregnancy. Demographic and maternal-fetal clinical data were obtained from the clinical histories and each center completed a data collection form created for this study. We defined a NL case (born or not) who presented, pre and/or postpartum, characteristic skin lesions, cytopenias, cardiac involvement (CHB, endocardial fibroelastosis and dilated cardiomyopathy), hepatic or neurological manifestations. Ethnicity was classified using the GLADEL group definitions. NL frequency was calculated dividing the number NL cases by the number of mothers with positive anti-Ro/La serology.

Results: 18 reference centers in the management of autoimmune diseases and pregnancy participated in this study in 7 different geographic areas of Argentina (6 from Buenos Aires, 6 from Cordoba, 1 from Jujuy, 1 from Mendoza, 1 from Santa Fe, 1 from Santiago del Estero and 2 from Tucuman). 193 mothers with positive anti-Ro/La serology were included with 364 pregnancies. 19 NL cases were reported (10 diagnosed during pregnancy and 9 in the post-partum period.) The frequency of NL was estimated at 9.8% [95% CI 6.3-14.9] (CHB=6.2% [IC95% 3.5-10.7].) The most frequent manifestations were skin (n=7) and cardiac involvement (n=12). In 1 case, there was a history of NL in a previous pregnancy. Of the patients with CHB, 5 required a pacemaker.

Conclusions: In conclusion, the frequency of NL in our multicentric cohort is greater than in other international cohorts. Differences could be related to genetic/environmental factors as well as methodological limitations and selection bias.

39

IMPROVING THE PERFORMANCE OF THE SPANISH VERSION OF QOL-RA

Carolina Isnardi¹, Dafne Capelusnik¹, Emilce Edith Schneeberger¹, María de los Ángeles Correa¹, Romina Lim², María Hu², María Janina Tapia³, Eduardo Kerzberg³, Eliana Soledad Blanco⁴, Federico Luján Benavidez⁴, Luciana Gonzalez Lucero⁵, Ana Lucía Barbaglia⁵, Marcela Bazzarelli⁶, Hernán Maldonado Ficco⁷, Silvana Perez⁸, Claudia Hartvig⁹, Mariana Salcedo¹⁰, and Gustavo Citera¹. ¹Instituto De Rehabilitación Psicofísica, Caba, Argentina, ²Hospital General de Agudos José M. Penna, CABA, Argentina, ³Hospital General de Agudos José María Ramos Mejía, CABA, Argentina, ⁴Hospital General de Agudos Dr. Cosme Argerich, CABA, Argentina, ⁵Hospital Ángel C. Padilla, San Miguel de Tucumán, Argentina, ⁶Hospital Interzonal General de Agudos Petrona V. de Cordero, Tigre, Argentina, ⁷Hospital San Antonio de Padua, Río Cuarto, Argentina, ⁸Hospital General de Agudos Dr. Enrique Tornú, CABA, Argentina, ⁹Hospital Provincial de Rosario, Rosario, Argentina, ¹⁰San Nicolás, San Nicolás, Argentina.

Objectives: We have recently validated the Quality of Life-Rheumatoid Arthritis Scale (QOL-RA). Redundancy between questions N° 3 and N° 6 was observed, and besides QOL-RA was influenced by age and disease duration. For this reason, with the author’s permission, we have changed these questions and developed a new version of Spanish QOL-RA.

The aim of our study was to validate this Spanish version in patients with Rheumatoid Arthritis (RA).

Methods: A cross-sectional multicenter study was carried out. Patients ≥18 years of age, with a diagnosis of RA according to ACR-EULAR 2010 criteria were included. Sociodemographic data, comorbidities, RA characteristics, disease activity current treatment were registered. Questionnaires were administered to assess quality of life by EQ-5D-3L and QOL-RA, functional capacity by HAQ-A and depression by PHQ-9. The time to complete and calculate both quality of life questionnaires was measured, and the difficulties that the patients presented to complete any item were recorded. The QOL-RA was re-administered in 20 patients to evaluate reproducibility. Patients with difficulties in answering the questionnaire (illiterate, blind) and with decompensated comorbidities were excluded. Statistical analysis: Student´s T, ANOVA and Chi² tests. Spearman correlation. Reliability by Cronbach´s alpha. Reproducibility using ICC. QOL-RA linear tendency based on RA activity by multinomial logistic regression with completed factorial model. Multiple linear regression.

Results: 430 patients were included. Median (m) disease duration was 8.9 years (IQR 4-16). m DAS28-ESR was 2.9 (IQR 1.9-3.9). m QOL-RA was 6.6 (IQR 5.3-8) and it had a good correlation with EQ-5D-3L (Rho: 0.6), PHQ-9 (Rho: -0.56), HAQ-A (Rho: -0.55) and DAS28-ESR (Rho: -0.4). Worse QOL-RA was observed in current smokers (mean 6.1±1.7 vs 6.6±1.9, p= 0.016), unemployed (mean 6.1±1.8 vs 6.9±1.8, p=0.0001) and patients not doing physical activity (mean 6.3±1.9 vs 7±1.9, p=0.0001). It showed very good reliability (0.97) and reproducibility (ICC= 0.96 IC 95% 0.90-0.99). Ceiling and floor effects were 2.8% and 0.7%, respectively. Only 0.9% of the questionnaires presented at least one missing answer. There was no redundancy between questions. Patients with higher disease activity had a significant poorer quality of life. In the multivariate analysis, disability, disease activity, and the presence of depression were independently associated to worse quality of life.

Conclusions: This new version of QOL-RA demonstrated better construct validity, reproducibility and reliability compared to the original version and it was easy to complete and calculate. It it was not influenced by age and disease duration.

75

A BREAKTHROUGH DIAGNOSTIC PROTEIN, 14-3-3 ETA, CAN HELP US IDENTIFY PATIENTS WHO WILL RESPOND TO INFLIXIMAB AND ITS BIOSIMILAR IN RHEUMATOID ARTHITIS?

Bogdan Ion Gavrila¹, Claudia Ciofu¹, Liviu Macovei¹, Ioan Ancuta¹, Mihai Bojinca¹, and Victor Stoica, Prof¹. ¹Department of Internal Medicine and Rheumatology Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

Objectives: Testing predictive value of 14-3-3 eta protein regarding response to Infliximab (IFX) and its biosimilar (Remsima) on 2 grups of patients diagnosed with rheumatoid arthritis (RA).

Methods: Longitudinal and observational study, including 2 groups of patients with active RA, uncontrolled by csDMARDs, followed 12 months,16 treated with IFX and 17 with Remsima. Clinical assessment was performed at 0,6,12 months according to ACR criteria and evaluation of treatment response according to EULAR criteria (good/moderate/nonresponder).

Results: 30 patients were women and 3 men. Following baseline 14-3-3eta titers and the response at 6 months, tests for identifying differences between groups showed that lower 14-3-3eta protein titers, in both groups of patients, had predictive value on achieving a good EULAR response at 6 months. For IFX, patients with good EULAR response had lower baseline titers(0.11±0.245 ng/ml) than patients with moderate response (0.70±0.705 ng/ml,p=0.049). For Remsima group, good responders had lower baseline titers (0.25±0.380 ng/ml) than nonresponders (1.67±0.615 ng/ml, p=0.004) or those with moderate response (0.25±0.401 ng/ml).

Grouping patients in 2 categories (responders/nonresponders) only for IFX group,14-3-3eta maintained value predicting a 6 months response (0.25±0.378 ng/ml) Vs. the nonresponders (1.67±0.615 ng/ml, p=0.0005).

For 12 months, we did not find significant differences between groups regarding baseline 14-3-3eta titers and the response obtained (IFXp=0.1483, Remsima p=0.2470). The status pretreatment(positive/negative) influenced the good response for IFX group at 6 months(p=0.005).

Regarding the evolution of serum titers, we noticed a reduction, statistically close to significance for IFX (baseline 0.51± 0.703 ng/nl,12months 0.13± 0.439, p=0.064), but not for Remsima(p=0.153).

Conclusions: 14-3-3 eta, a new diagnostic biomarker, could be a major candidate to distinguish pretreatment patients who will or not respond to anti-TNF α therapy.

76

CARTILAGE OLIGOMERIC MATRIX PROTEIN, A BIOMARKER OF ARTHRITIS, COULD IT BE USEFUL FOR PREDICTING THE RESPONSE TO BIOLOGIC THERAPY IN RHEUMATOID ARTHRITIS?

Claudia Ciofu¹, Liviu Macovei¹, Ioan Ancuta¹, Mihai Bojinca¹, Victor Stoica¹, and Bogdan Ion Gavrila¹. ¹Department of Internal Medicine and Rheumatology, “Dr. I. Cantacuzino” Clinical Hospital, Carol Davila University of Medi, Bucharest, Romania.

Objectives: Evaluating the predictive role for the response to anti-TNF α of cartilage oligomeric matrix protein (COMP), a biomarker which evaluates the articular cartilage degradation and its turnover.

Methods: Observational study including 64 patients followed 12 months with active RA, uncontrolled by csDMARDs. Clinical assessment was performed at 0,6,12 months according to ACR criteria approved by OMERACT and evaluation of treatment response according to EULAR criteria (good/moderate /nonresponder).

Results: 64 patients included. After 6 months,7 patients were declared nonresponders, 38 achieved a moderate response and 19 a good response. Following baseline COMP titers and the EULAR 6-month response, general tests identified significant differences between groups. Lower baseline titers had predictive value for achieving a good response (746.04±130.095 ng/ml) comparing with moderate responders (1032.8±188.671ng/ml) and nonresponders (1042.2±181.717 ng/ml, p=0.000). After 12 months,11 patients achieved moderate response,44 good response and just 1 patient was declared nonresponder. At this visit, even if we did not find significant differences between baseline COMP titers and the EULAR response (p=0.1430), we observed lower baseline titers for good responders (917.8±219.943 ng/ml) vs moderate responders (1042.7±193.117 ng/ml). Grouping patients’ responders/nonresponders there were no differences between groups at 6 months (p=0.227) or 12 months (p=0.9753). Following the status pretreatment of COMP and EULAR response at 6 months, we identified differences between groups (p=0,0001), all 7 nonresponders patients were COMP positive and only 13/19(68.4%) of good responders were tested positive. At 12 months there were no differences between groups (p=0.2805).

Conclusions: COMP could be one of the biomarkers for identifying pretreatment the patients who will respond to anti-TNF therapy in RA.

122

LOW SKELETAL MUSCLE MASS RELATIVE TO ADIPOSITY IS ASSOCIATED WITH DISEASE ACTIVITY STATUS AND PHYSICAL FUNCTIONING IN RHEUMATOID ARTHRITIS

Rafaela Santo^1,2, Jordana Miranda de Souza Silva^1,2, Joshua Baker³, Vanessa Hax^1,2, Claiton Viegas Brenol^1,2, Lidiane Isabel Filippin⁴, Priscila Lora⁵, and Ricardo Machado Xavier^1,2. ¹Universidade Federal do Rio Grande Do Sul, Porto Alegre, Brazil, ²Serviço de Reumatologia do Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, ³University of Pennsylvania, Philadelphia, United States, ⁴Universidade La Salle, Canoas, Brazil, ⁵Universidade do Vale do Rio dos Sinos, São Leopoldo, Brazil.

Objectives: To assess muscle mass relative to fat mass and verify the associations of this parameter with disease activity status, functional capacity and biologics treatments.

Methods: 90 RA patients, aged between 40 and 70 years, were recruited and followed for 12 months. Body composition was assessed by total body dual-energy x-ray absorptiometry for measurement of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2). Age-, sex-, and race-specific Z- Scores and T-Scores were determined by comparison to published reference ranges. ALMI values were adjusted for FMI (ALMIZ/FMIZ) using a published method. Disease activity was assessed by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28). RA patients were divided in non-remission (DAS28>2.6) and in remission (DAS28<2.6). Physical functioning was assessed by the Health Assessment Questionnaire (HAQ). Pharmacological treatment used was assessed from the patient’s medical records; RA patients were divided into RA patients treated with biologic disease modifying antirheumatic drugs (bDMARDs) and non-treated with bDMARDs. Frequency analysis, Pearson Correlations and GEE analyses were used, and statistical significance was considered as p<0.05.

Results: Of the 90 patients analyzed, most were women (86.7%,78/91), with mean age of 56.5±7.3 and median disease duration time of 8.5 (3-18) years. At baseline, the mean±SD DAS28 score was 3.7±1.4 and thirty percent of the RA patients (27/90) were treated with bDMARDs. After 12 months, the use of bDMARD did not change (p>0.05), however, mean DAS28 increased over time (mean and SD of 4.0±1.3; p<0.05). Eleven RA patients (12.2%) showed low ALMI/FMI for age (Z-score ≤-1) at baseline, and 13 (16.0%) after 12 months. After 12 months, ALMIZ/FMIZ was inversely associated with HAQ (r=-0.3; p<0.05). At, baseline, women in remission had higher ALMIZ, lower FMIZ and higher ALMIZ/FMIZ, while men had lower ALMIZ, lower FMIZ and higher ALMIZ/FMIZ. In men, remission was associated with decreases in FMIZ (p<0.05). The use of bDMARDs was not related with alterations in ALMIZ, FMIz and ALMIZ/FMIZ (p>0.05).

Conclusions: Low skeletal muscle mass relative to adiposity was common in RA patients. This condition was associated with low physical functioning and its changes over time are associated with disease activity status. The observations that skeletal muscle mass relative to adiposity was affected by remission state and that it associated negatively with poor physical functioning, demonstrates the importance of adequate control of disease activity in patients with establishedRA. In addition, from our results, further studies are necessary to elucidate the direct impact of bDMARDs on body composition in RA patients.

FINANCIAL SUPPORT: CAPES, CNPq, FAPERGS, FIPE-HCPA.

195

BARICITINIB: EARLY VS DELAYED START IN PATIENTS WITH RHEUMATOID ARTHRITIS

Peter Taylor¹, Yoshiya Tanaka², Anabela Cardoso³, Jinglin Zhong⁴, Yun-fei Chen³, Jennifer Workman³, Liliana del Carmen Morales⁵, Michael Schiff⁶, and Diana Gómez⁵. ¹Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Botnar Research Centre Oxford, Oxford, UK, ²The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, ³Eli Lilly and Company, Indianapolis, IN, USA, ⁴IQVIA, Morrisville, NC, USA, ⁵Instituto Reumatológico Strusberg, Córdoba, Argentina, ⁶University of Colorado School of Medicine, Denver, CO, USA.

Objectives: The objective of this analysis was to assess if patients (pts) receiving baricitinib (BARI) early gain added clinical improvement compared to pts with delayed start of therapy.

Methods: In RA-BEAM, 1305 pts were randomized 3:3:2 to PBO, BARI-4 mg QD, or adalimumab (ADA) 40 mg every 2 weeks. At Week 24, PBO pts were switched to BARI-4 mg. Patients initially randomized to BARI-4 mg were the early start group and PBO pts rescued at Week 16 or switched at Week 24 or later were considered delayed start. Change from baseline in Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), DAS28-hsCRP, DAS28-ESR, HAQ-DI, and modified total Sharp score (mTSS) were compared between early vs delayed start groups between Weeks 24 and 52.

Results: The early start group had significantly greater change from baseline up to Week 32 with greater and more rapid reduction through first 4 weeks (>50% reduction) for CDAI compared to the delayed start group. At Week 24, the delayed start group showed similar reduction in CDAI as the early start group between Weeks 4 and 8 giving the early start group a 4 to 5-month advantage in disease improvement. After receiving BARI, the delayed start group also showed a rapid improvement in CDAI and caught up to the early start patients by Week 40. Similar results were seen for SDAI, DAS28-ESR, and DAS28-hsCRP. The early start pts maintained significantly greater improvement in HAQ-DI at Week 40 and a significant advantage from Weeks 16 to 52 for mTSS.

Conclusions: While overall disease activity improvement was similar, early start of BARI provided faster efficacy. A delay of up to 6 months in BARI treatment affected HAQ-DI and structural damage progression.

219

A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY COMPARING UPADACITINIB MONOTHERAPY TO MTX MONOTHERAPY IN MTX-NAÏVE PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS

R. van Vollenhoven¹, T. Takeuchi², A.L. Pangan³, A. Friedman³, M.F. Mohamed³, S. Chen³, M. Rischmueller⁴, R. Blanco⁵, R.M. Xavier⁶, and V. Strand⁷. ¹Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, the Netherlands, ²Keio University School of Medicine, Tokyo, Japan, ³AbbVie Inc, North Chicago, USA, ⁴The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Austrailia, ⁵Hospital Universitario Marqués de Valdecilla, Cantabria, España, ⁶Universidade Federal do Rio Grande do Sul Porto Alegre, Rio Grande do Sul, Brazil, ⁷Stanford University, Palo Alto, USA.

Objectives: To compare the clinical efficacy, including inhibition of structural damage, and safety of upadacitinib (UPA), a JAK1-selective inhibitor, as monotherapy, vs methotrexate (MTX) monotherapy, in MTX-naïve patients (pts) with moderate to severely active rheumatoid arthritis (RA) at high risk for structural progression.

Methods: In SELECT–EARLY, MTX-naïve pts with active RA who were positive for both RF and ACPA and/or had ≥1 joint erosion was randomized 1:1:1 to once-daily (QD) UPA at 15mg or 30mg, or weekly (wk) MTX (titrated by Wk8). Separate primary endpoints were ACR50 at Wk12 (FDA), or the proportion of pts achieving DAS28CRP <2.6 at Wk24 (EMA). Secondary endpoints included change from baseline (BL) (Δ) in modified Total Sharp Score (mTSS≤0) and proportion of pts with no radiographic progression at Wk24.

Results: 945/947 patients were treated; 88.7% completed Wk24. All primary and secondary endpoints were met. Significantly more patients on UPA15 and 30mg vs MTX achieved Wk12 ACR50 (52.1% and 56.4% vs 28.3%) and Wk24 DAS28CRP <2.6 (48.3% and 50.0% vs 18.5%). At Wk24, mean ΔmTSS was 0.14 and 0.07 vs 0.67 (UPA 15/30 mg vs MTX) and more patients had no radiographic progression on UPA. More patients on UPA vs MTX achieved LDA and remission.

Rate of AEs and SAEs were similar on UPA15 and MTX, and higher on UPA 30. AEs leading to discontinuation were similar across arms. More patients on UPA30 reported serious infections. Herpes zoster was higher on UPA vs MTX. Four malignancies, 4 major adverse cardiovascular events (MACE), and 6 deaths were reported (MTX: 1 sudden [CV]; UPA15: 1 CV, 1 metastatic malignant melanoma; UPA30: 1 CV, 1 pneumonia and sepsis, 1 peritonitis). Two VTE were reported (MTX:1 PE, UPA30:1 DVT).

Conclusions: In MTX-naïve pts at high risk for structural progression, UPA at 15 and 30mg QD demonstrated significant and clinically meaningful improvements in RA signs & symptoms vs MTX. Radiographic progression was significantly lower with UPA vs MTX. Safety events were consistent with Phase 2 and 3 studies with UPA in RA to date.

130

SUSTAINED IMPROVEMENTS IN SIGNS AND SYMPTOMS OF ACTIVE ANKYLOSING SPONDYLITIS AND REASSURING SAFETY WITH SECUKINUMAB 300 MG: 3-YEAR RESULTS FROM A PHASE 3 STUDY

Marco Maradiaga Ceceña¹, Alan J Kivitz², Karel Pavelka³, Eva Dokoupilova^4,5, Ricardo Blanco⁶, Hasan Tahir⁷, Yi Wang⁸, Brian Porter⁸, Anna Stefanska⁹, Susanne Rohrer¹⁰, and Hanno Richards¹⁰. ¹Centro de Investigación de Tratamientos Innovadores de Sinaloa, Culiacán, México, ²Altoona Center for Clinical Research, Duncansville, USA, ³Institute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, ⁴MEDICAL PLUS s.r.o., Uherske Hradiste, Czech Republic, ⁵University of Veterinary and Pharmaceutical sciences, Faculty of Pharmacy, Department of Pharmaceutics, Uherske Hradiste, Czech Republic, ⁶Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, España, ⁷Barts Health NHS Trust, London, UK, ⁸Novartis Pharmaceuticals Corporation, East Hanover, USA, ⁹Novartis Ireland Limited, Dublin, Ireland, ¹⁰Novartis Pharma AG, Basel, Switzerland.

Objectives: Secukinumab (SEC) provided significant and sustained improvement in the signs and symptoms of ankylosing spondylitis (AS) over 2 years in the MEASURE 3 study (NCT02008916). Here we report 3-year end-of-study results.

Methods: 226 patients (pts) were randomized to intravenous (IV) SEC 10 mg/kg (baseline, Weeks (Wks) 2 and 4) followed by subcutaneous (SC) SEC 300 or 150mg every 4 wks (IV→300/150mg), or matched placebo (PBO). At Wk 16, PBO pts were re-randomized to SC SEC 300 or 150mg. Analysis at Wk 156 included pts initially randomized to SEC and those who switched from PBO to SEC at Wk 16 (Any SEC 300mg, N = 113 and Any SEC 150mg, N = 110). Outcomes at Wk 156 included ASAS20/40, hsCRP, BASDAI, ASAS partial remission (PR) and ASDAS-CRP inactive disease. Analyses stratified by TNF α inhibitor (TNFi)-naïve and TNFi inadequate response [IR] status were pre-specified. Data are reported as observed. Safety analyses included all pts who received ≥1 dose of SEC.

Results: 80.5% (91/113; Any SEC 300mg) and 80.9% (89/110; Any SEC 150mg) pts completed 156 wks of treatment. ASAS20/40 response rates at Wk 156 were 75.0%/ 56.5% in the Any SEC 300mg and 68.2%/47.7% in the Any SEC 150mg groups. Sustained improvements were also observed across all other endpoints through Wk 156. Response rates on more stringent clinical endpoints (eg ASAS40, ASAS PR) were higher with the 300mg dose, particularly in TNFi-IR pts. The safety profile was similar through Wk 156 for both SEC doses. Exposure-adjusted incidence rates for Candida and serious infections were 0.7 and 0.7 per 100 patient-years, respectively, in the combined SEC group over the entire treatment period. No cases of inflammatory bowel disease, including Crohn's disease or ulcerative colitis, were reported, and no deaths occurred.

Conclusions: SEC (300 and 150mg) provided sustained improvements through 3 years in the signs and symptoms of active AS, with greater responses observed with the 300 mg dose. The safety profile of SEC was consistent with previous reports.

138

SECUKINUMAB PROVIDES SUSTAINED IMPROVEMENTS IN THE SIGNS AND SYMPTOMS OF ACTIVE PSORIATIC ARTHRITIS: LONG-TERM (4-YEAR) DATA FROM A PHASE 3 STUDY

Iain B. McInnes¹, Alan J. Kivitz², Peter Nash³, Proton Rahman⁴, Jurgen Rech⁵, Bruce Kirkham⁶, Sandra Navarra⁷, Kevin Ding⁸, Emma Ilsley⁹, and Luminita Pricop⁸. ¹University of Glasgow, Glasgow, United Kingdom, ²Altoona Center for Clinical Research, Duncansville, United States, ³University of Queensland, Brisbane, Australia, ⁴Memorial University, St. John's, Canada, ⁵Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Monash University, Erlangen, Germany, ⁶Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom, ⁷University of Santo Tomas Hospital, Manila, Philippines, ⁸Novartis Pharmaceuticals Corporation, East Hanover, United States, ⁹Novartis Pharma AG, Basel, Switzerland.

Objectives: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, provides sustained improvement in the signs and symptoms of active psoriatic arthritis (PsA). ¹ Here we report long-term (4-yr) efficacy and safety results in patients from FUTURE 2 study.

Methods: Overall, 397 patients with active PsA were randomized to either secukinumab (300, 150, or 75 mg) or placebo weekly, followed by every 4 weeks (wks) starting at Wk 8.¹ Approximately 1/3 of patients had inadequate response [IR] to prior anti-TNF use. Pts were escalated from 150 to 300 mg and from 75 to 150/300 mg starting at Wk 128, if active signs of inadequate control of disease were observed. Assessments at Wk 208 included ACR20/50/70, PASI 75/90, HAQ-DI, SF-36 PCS, and resolution of dactylitis/enthesitis. Analyses by prior anti-TNF use (naïve/IR) and with/without concomitant methotrexate were assessed. Safety analysis included all patients who received ≥1 dose of secukinumab.

Results: Overall, 69/100 (69%), 70/100 (70%), and 62/99 (63%) patients originally randomized to secukinumab 300, 150, and 75 mg, respectively, completed 208 wks of treatment; 46/100 (46%) patients in the 150 mg group were escalated to 300 mg and 56/99 (57%) patients in the 75 mg group escalated to 150/300 mg. Clinical responses were sustained through Wk 208. In the overall population response rates at Wk 208 in the 300, 150, and 75 mg groups were 71.2%, 75.0% and 69.4% for ACR 20, and 80.6%, 81.4% and 66.7% for PASI 75, respectively; the proportion of patients with complete resolution of enthesitis/dactylitis were 70.7%/85.3%, 71.7%/88.0% and 64.4%/92.3%, respectively. In patients who had dose-escalation, the proportion of non-responders and ACR20 responders decreased, with corresponding increases in the proportion of patients achieving ACR50/70 responses. The type, incidence, and severity of adverse events with secukinumab were consistent with previous reports. ¹

Conclusions: Secukinumab 300 and 150 mg provided sustained improvement in the signs and symptoms of PsA over 4 yrs. Secukinumab was well-tolerated, with no new/unexpected safety signals.

References:

1 McInnes IB, et al. Rheumatology (Oxford). 2017;56:1993–200.

179

BIOLOGIC TREATMENT INDICATIONS IN PATIENTS WITH SPONDYLOARTHROPATHIES IN ARGENTINA. IS THERE A GAP BETWEEN TREATMENT INDICATION AND TREATMENT RECEIVED?

José Maximiliano Martínez Pérez¹, Dafne Capelusnik², Carolina Isnardi², Marina Scolnik¹, Gustavo Citera², and Enrique Soriano¹. ¹Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina, ²Instituto de Rehabilitación Psicofísica, Ciudad Autónoma de Buenos Aires, Argentina.

Objectives: 1) We determined the percentage of patients with PsA and AS who complied with the indication of biological treatment in accordance with international guidelines and the percentage of patients who received it.

2) We identify important gaps for access to biological treatment in these groups of patients and

3) We consider possible solutions to improve access.

Methods: During a two-month period, patients with PsA and AS were evaluated. Compliance with the indication of biological treatment was evaluated according to international clinical guidelines, GRAPPA for PsA and ASAS for AS. The demographic, socioeconomic and clinical characteristics were evaluated. A qualitative analysis (QA) was developed to identify the perception of access barriers to patients. Data on compliance with treatment guidelines were obtained from medical records. In-depth interviews with patients with clear indication of biological products, but not receiving them, were done to better understand patients' beliefs about their disease, how to deal with their disease, their knowledge about their treatment options and their knowledge about access to treatments in general.

Consecutive patients with PsA and AS were evaluated from the outpatient clinics of two rheumatological centers: Hospital Italiano de Buenos Aires (private hospital, PrH) and Institute of Psychophysical Rehabilitation (publichospital, PuH). This study was sponsored by Novartis.

Results: 200 patients were included, 100 with PsA and 100 with AS.

Among all patients with PsA 55 fulfilled GRAPPA criteria to receive biologics, but only 39 of them (71%) received that treatment. There were significative differences between PrH and PuH in the percentage of patients fulfilling criteria. This agrees with patients in the PuH being more active.

Among all patients with AxSpA 57 fulfilled ASAS criteria to receive biologics, but only 35 of them (61%) received that treatment. Only 30% of patients fulfilling criteria in the PuH received biologics, while 93% of those in the PrH received them (p=0.001)

The major reasons for this gap were the refusal to approve the medication by the payer, and the patient’s refusal to receive the new medication, and in AS patients the physician not prescribing it.

Conclusions: In summary there is a gap between criteria for biologics and the actual prescription of biologics. The main reason for not receiving biologics was refusal from the payer and the patient. There were some differences between a private hospital with higher access and a public hospital, and also between PsA and SpA. We still need to work on patient’s education, patients-physicians communication, accessibility, and primary care physicians.

324

AUTOIMMUNE CYTOPENIAS AND POLYAUTOIMMUNITY IN JUVENILE COLOMBIAN PATIENTS

Clara Malagón¹, Maria del Pilar Gómez¹, Catalina Mosquera¹, Camilo Vargas¹, Tatiana González¹, Cristine Arango¹, Lorena Martin¹, and Pilar Pérez¹. ¹Grupo investigación GRIP. Universidad El Bosque, Bogotá, Colombia.

Objectives: Autoinmune cytopenias are common in pediatric patients. Organ specific and systemic autoimmune diseases (AD) share several pathogenic mechanisms and clinical features that may predispose the co-occurrence of more than one AD within an individual. Polyautoimmunity has been documented on adult and juvenile patients. Multiple autoimmune syndrome is the association of three or more AD. From a registry of 317 patients followed at 15 pediatric rheumatology clinics.

Methods: According to diagnostic criteria, the AD was classified. The index disease was the first AD diagnosed. If the diagnosis was confirmed with an interval less than six months they were classified as simultaneous, if this period was longer, otherwise. The clinical, serologic and the types of associations were determined.

Results: n= 22/317. Female predominance (F22: M1) and wide range of age of onset (1-16 y) were observed in autoinmune hemolytic anemia, autoinmune thrombocytopenia and autoinmune leucopenia. 60% had a positive family history of AD. Al cytopenias were always the index disease and the mean interval between first and second AD was 30,3 but the additional intervals were longer. The only male patient developed AI leucopenia and Hashimoto simultaneously. 3 patients developed bicytopenia during follow up. ITP was the most common index hematological AD (n=18 / 317), followed by Autoimmune leucopenia (3/317) and AI Hemolytic anemia (1/317). Patients with Evans syndrome and cytopenias associated to antiphospholipid antibodies were not included because they were classified as APLS. Multiple associations of AD were documented during follow up.

Conclusions: Autoimmune cytopenias may precede, coincide or follow additional organ specific and systemic AD and even develop MAS. Due to the fact that autoinmune cytopenias may be the index AD in polyautoimmunity, those patients require a close follow up of the clinical course and serologic profile. The intervals between 1° and 2° AD were prolonged. Hematological manifestations are the most common no thrombotic complications of APLS and must be ruled out at onset and during follow up seroconversion of antiphospholipid antibodies has been documented.

263

EFFICACY OF INTRAARTICULAR APPLICATION IN KNEES OF PLATELET-RICH PLASMA PLUS MEDICAL OZONE, IN PATIENTS WITH RHEUMAUTOID ARTHRITIS AND CLINICAL SYNOVITIS OF THE KNEES REFRACTORY TO CONVENTIONAL TREATMENT

Jenny Anali Yafac Serrano¹, Carlos Efrain Huanqui Guerra¹, Katherin Paucar Valdivia and Franz Diego Zevallos Zúñiga. ¹Hospital Honorio Delgado Espinoza, Arequipa, Perú.

Objectives: To evaluate the efficacy of intraarticular application in the knees of platelet-rich plasma (PRP) plus medical ozone (MO), in patients with rheumatoid arthritis (RA) and clinical knees synovitis refractory to conventional treatment.

Methods: 30 patients with RA and refractory knee synovitis of both sexes were selected for the study. All had definitive diagnosis of RA (DAS 28 ≥2.8) and refractory synovitis of the knees, resistant to conventional RA therapy. The knees were radiographically evaluated, presenting osteoarthritis (OA) grade II to III according to the Kellgren-Lawrence scale.

Treatment consisted of applying 3 cc of PRP and 3 cc of MO at a concentration of 20 μg / ml, in both knees, in 3 doses, once a week.

For the clinical evaluation of knees, visual analogue scale (VAS) was used before, after one month and one year after treatment; in some cases, ultrasonography was also used.

For the comparison of the clinical scores, the VAS scale was used and in the statistical analysis the Student's t test for repeated measurements was used; a p <0.05 was considered as significant.

Results: Of the 30 patients, 1 was a man and 29 were women, with an average age of 58 years. There was clinical improvement in knees according to the VAS scale, with an average of 6.5 at the beginning, 4.86 at one month and 3.43 a year after treatment (p <0.05), figure 1. According to the patients, there was improvement of functional capacity in ambulation in 80% of cases.

There was a decrease in hypertrophy and synovial effusion in all patients (20% of the total) who underwent ultrasonography on their knees one year after treatment.

Conclusions: The application of combination therapy of PRP plus MO in RA patients with refractory synovitis of the knees to conventional medication treatment and physioteraphy, is effective, simple, safe, low cost treatment and can lead to avoid remplacement surgery of the knee.

230

PANLAR STUDY GROUP CONSENSUS FOR A REPORT ON CAPILLAROSCOPY

Chiara Bertolazzi¹, Marwin Gutierrez¹, Angelica Vargas², Tatiana Sofía Rodríguez-Reyna³, Hugo Sandoval¹, Everardo Álvarez-Hernández⁴, Marcelo Audisio⁵, Eduardo Cabello⁶, Paola Coral⁷, Ericka Díaz⁸, Virginia Duringa, Karinna Espejo⁹, Selma Gallegos¹⁰, Gabriela Hernández-Molina³, Blanca Herrera⁸, Cristiane Kayser¹¹, María Eugenia Lara¹², Genessis Maldonado¹³, Marta N. Mamani¹⁴, Alejandro Nitsche¹⁵, Carlos Ríos-Acosta¹⁶, Félix Enrique-Romanini¹⁴, María Sormani de Fonseca¹⁴, Verónica Vilela¹⁷, Miguel Villarreal^1,8. ¹Instituto Nacional De Rehabilitación, Tlalpan, Mexico, ²Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, México, ³Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, México, ⁴Hospital General de México Dr. Eduardo Liceaga, México, ⁵ Hospital Nacional de Clínicas de la Universidad Nacional de Córdoba, Argentina, ⁶Hospital Nacional Alberto Sabogal Sologuren, Perú, ⁷Universidad Nacional de Colombia, Colombia, ⁸Sociedad Chuquisaqueña de Reumatología, Bolivia, ⁹Centro de Excelencia en Reumatología, Perú, ¹⁰Hospital Dr. Darío Fernández Fierro, México, ¹¹Universidade Federal de São Paulo (UNIFESP), Brazil, ¹²Lagomaggiore's Hospital, Argentina, ¹³Universidad Espíritu Santo, Ecuador, ¹⁴Hospital Rivadavia, Argentina, ¹⁵Instituto de Rehabilitación Psicofísica, Argentina, ¹⁶Rheumatology and Rehabilitation Center, Ecuador, ¹⁷University Hospital Pedro Ernesto, Brazil, ¹⁸Hospital Universitario Dr. José Eleuterio González, México.

Objectives: Introduction: Capillaroscopy (CAP) has progressively gained a central role in daily rheumatology clinical practice thanks to its non-invasiveness, the fact that it is well accepted by patients, and to the flourishing scientific evidence of its relevant role in the diagnosis and assessment of Raynaud´s phenomenon and systemic sclerosis and various rheumatic disorders. However, there are neither guidelines nor consensus for the format and content of the CAP report in rheumatology, which represents an integral and crucial aspect of the CAP examination.

Objectives: The aim of this work was to produce a consensus-based recommendations report for capillaroscopy in rheumatology to be used in daily clinical practice.

Methods: A written Delphi questionnaire regarding capillaroscopy reporting was developed from a literature review and expert consensus. The Delphi questionnaire was sent to 30 rheumatology experts in capillaroscopy around Latin-America (LA), asking them to rate their level of agreement or disagreement with each statement. The exercise consisted of three rounds and a final presential round that took place during the 2018 PANLAR congress held in Buenos Aires, Argentina.

Results: The participants to the first, second, third and presential rounds were 23, 22, 22 and 16, respectively. Fifty-five items were discussed in the first round, 58 in the second, 22 in the third and 10 in the presential meeting. At the end of the exercise, 40 recommendations for capillaroscopy reporting in rheumatology reached consensus.

Conclusions: The PANLAR capillaroscopy study group initiative has produced the first expert consensus for the format and content of CAP reporting in rheumatology. The building of a consensus report in CAP responded to a need expressed by teachers and experts to have a clinical instrument to use in daily practice.

298

ULTRASOUND FINDINGS IN HEALTHY ADULTS: AN OMERACT’S EXPERIENCE AT THE NATIONAL INSTITUTE OF REHABILITATION

Luis Carlos Rodriguez Delgado¹, Gustavo Leon², Cristina Reátegui³, Jaime Mendoza¹, Jessica Gutiérrez¹, Héctor García¹, Araceli Bernal¹, Denise Clavijo¹, Chiara Bertolazzi¹, Carlos Pineda¹, Marwin Gutierrez¹. ¹Instituto Nacional De Rehabilitación, Ciudad De México, México, ²Hospital Edgardo Rebagliati Martins, Lima, Perú, ³Hospital Guillermo Almenara, Lima, Perú.

Objectives: To describe the ultrasound findings of hands and feet in healthy subjects.

Methods: The study included healthy subjects over 18 years of age without the presence of musculoskeletal symptoms who underwent US examination of hands and feet. In order to evaluate if the US findings are influenced by age, we stratified the subject into two groups: A) younger than 40 yearsand B): older than 40 years. An expert US rheumatologist scanned the dorsal surface of the 32 joints (metacarpophalangeal, proximal interphalangeal, and metatarsophalangeal, 1st to 5th and the wrist bilaterally) and 12 tendons (extensor carpi ulnaris and digital flexors of the hand).

Synovial hypertrophy (SH), synovial effusion (SE), erosions and osteophytes were assessed by both grey-scale (GS) and power Doppler signal (PD). For the scanning technique and definitions, the EULAR/OMERACT were adopted.

Results: A total of 60 healthy subjects were included (40 for group A and 20 for group B). SE was identified in 38 (91%) subjects in group A, and in 20 (100%) in group B; while SH was found in 3 (7.5%) subjects in group A and 18 (90%) in group B (p= 0.001). On the other hand, osteophytes were found in 18 (30%) subjects from group A and in 20 (100%) in group B (p= 0.001). Tenosynovitis was detected in 10 (50%) healthy group B subjects and in 2 (5%) in group A (p= 0.001), in both cases the extensor carpi ulnaris was predominant (14). The PD signal was identified in 2 (1%) subjects in group A and in 4 (1%) for group B. Finally, erosions were found in 3 (7.5%) in group A and in 3 (15%) in group B.

Conclusions: The study showed a wide range of US abnormalities in healthy subjects including SE, SH, even PD which varied according with age. This information is useful for the rheumatologist when performing an US, and for establishing an US threshold abnormality for physiological and pathological variants.

ELECTRONIC POSTERS

264

HIGH SERUM ADIPOKINES LEVELS, PERIODONTAL INFECTION AND RHEUMATOID ARTHRITIS: COINCIDENCE OR A MORE COMPLEX RELATIONSHIP?

Consuelo Romero-Sánchez^1,2,3, Juliette De Avila³, Andrea Chaparro-Sanabria², Alejandro Ramos-Casallas³, Lorena Chila-M³, Nataly Delgadillo³, Philippe Chalem-Ch⁴, Wilson Bautista-Molano^2,3, and Juan Manuel Bello-Gualtero^1,2. ¹Rheumatology and Immunology Department Hospital Militar Central / Universidad Militar / Universidad El Bosque, Bogotá, Colombia, ²Clinical Immunology Group-School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia, ³Unit of Oral Basic Investigation, School of Dentistry, Universidad El Bosque, Bogotá, Colombia, ⁴Fundación Instituto de Reumatología Fernando Chalem, Bogotá, Colombia.

Objectives: Recent advances on the role of the adipokine network in the pathogenesis of Rheumatoid Arthritis (RA) and the possibility of using circulating levels of adipokines as potential biomarkers of disease activity has been described. Similarly, it has been shown that obesity is associated with periodontitis. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic crosslink. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on RA. The aim was to establish the association of the adipokines levels with rheumatic activity, Body Mass index (BMI) and periodontal infection.

Methods: A cross sectional study was conducted. 62 patients with early-RA (eRA) according to the ACR/EULAR2010 criteria and 62 healthy controls matched by age and gender were included. A complete medical history was obtained. Adiponectin, adipsin, resistin and vaspin levels were measured using Luminex technology, IL6 and leptin by ELISA. Serum markers such as RA, ESR, CRP, and APCA were evaluated. Disease activity was evaluated by DAS28CRP, DAS28ESR, SDAI and RAPID3.Porphyromonas gingivalis (P. gingivalis) by qPCR. An association analysis was made to evaluate the relationship between adipokines levels, rheumatologic activity, BMI and P. gingivalis using Chi square, Fisher’s Exact or U Mann Whitney test. A logistic regression model was performed to confirm associations. All analyses were performed using IBM-SPSS V25 for Windows with a level of significance of 95%.

Results: In the eRA group, 81.1% were women; their mean age was 48.9±10.9 years; 39.6% were overweight, 13.2% were obese and 85.2% had ACPA>20UI. In the controls 79.6% were women, with a mean age of 48.2±11.1 years; 24.5% were overweight and 6.1% were obese(p=0.028). 39.6% of eRA patients showed moderate activity and 13.2% high activity by DAS28ESR(p=0.001). In eRA, high levels of Leptin were three times more frequent (75.6%) than controls (24.4%) p=0.001; similarly, for adipsin high levels were present in 62.5% of eRA Vs 37.5% in controls, p=0.049. Despite the absence of significant differences for periodontitis among groups it was observed a high frequency of P.gingivalis in eRA 63.5% compared to controls(p=0.004).Patients who showed ACPA>20UI and P.gingivalis simultaneously, exhibited high levels of leptin(OR:8.22;CI95%2.75-24.50;p=0.001), high levels of adipsin(OR:3.06;CI95%1.05-8.97;p=0.041) and DAS28ESR>3.2(OR:2.59;CI95%1.46-4.58;p=0.001). Likewise, patients who concurrently present P. gingivalis, DAS28ESR>3.2, CRP>3.0mg/L and BMI>25 also showed an association with high levels of leptin and adipsin (OR:7.20; CI95%2.6819.33; p=0.0001 and OR:2.69; CI95%1.00-7.28; p=0.005 respectively).

Conclusions: High levels of leptin and adipsin are associated with greater clinical activity in patients with RA in early stages and periodontal infection. These adipokines could be a pathomechanistic link whereby obesity and P gingivalis enhance the risk of clinical activity in eRA.

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PREVALENCE OF DAMAGE IN A LATIN AMERICAN MYOSITIS POPULATION COHORT AND ITS CORRELATION WITH THE USE OF STEROIDS

Olivia Enríquez-Antonio¹, Lilia Andrade-Ortega¹, and Fedra Irazoque-Palazuelos¹. ¹Departamento de Reumatología, CMN 20 de Noviembre, ISSSTE., Ciudad de México, México.

Objectives: The damage score MDI-MYODAM has been recently developed to measure the damage of immune mediated myopathies (IMM). The few publications reporting damage measured by MDI-MYODAM included only Caucasian populations with IMM and found a prevalence of 92%.

There are no studies in Mexican or Latin American populations about the degree of damage related to IMM nor about its correlation with disease activity, association with other comorbidities, duration of disease, type of myopathy, or therapeutic history.

To determine the prevalence of damage measured by MDI-MYODAM in patients with IMM from a Mexican population and the relationship with characteristics of the disease and comorbidities.

Methods: With previously informed consent, we applied both sections of MDI-MYODAM to the cohort of IMM patients of our department. We used formal questionnaires to evaluate demographic variables, characteristics of the disease, activity of the disease (MITAX), therapeutic history, and comorbidities (Charlson index). Descriptive statistics were used with bivariate Spearman, Pearson, or Students t correlations according to the case. p<0.05 was considered as a statistically significant value.

Results: 53 myositis patients were assessed, 75.5% were women. Mean age at diagnosis: 40.7±16.78 years and mean duration of disease: 11.8±8.28 years. 32.07% of patients had polymyositis, 32.07% dermatomyositis, 11.32% juvenile dermatomyositis, 9.43% of patients overlapped with systemic lupus erythematosus, scleroderma or rheumatoid arthritis. Charlson index in total population was 2.72±2.38.

With MDI: 84.9% of the patients had damage, with a score > 0 for at least one category, most in endocrine (54.7%), skeletal (45.2%), or gastrointestinal (37.7%) systems, with a mean total damage score of 3.58±2.87. In MYODAM the mean score for total damage was 6.85±5.06. 13.76% of patients had some degree of disease activity as defined by MITAX.

We found direct correlation between MDI score and chronic use of steroids (r 0.34, 95%CI 0.071-0.567, p<0.014). We could not find association of damage with activity 4.29±4.60 vs no activity 3.47±2.59, p=0.55, nor with the type of myopathy or baseline CK.

Conclusions: Most of our patients with IMM had some type of damage, even from the earliest stages of the disease, with greater impact in endocrine, skeletal and gastrointestinal systems. Patients with chronic or relapsing course tend to have more damage. As expected there was a correlation between damage and comorbidities.

The results of our work indicate that damage increases with the duration of the disease and the use of steroids in a non-linear way.

These results highlight the benefits of a better control of the disease with steroid-sparing treatments.

66

RISK OF HEART VALVE DISEASE IN SYSTEMIC SCLEROSIS

Rodolfo Nicolas Alvarado¹, Marina Scolnik¹, Nicolas Martin Marin Zucaro¹, Gelsomina Alle¹, María Soledad Trasante Borches¹, María Victoria Chiarvetto Peralta¹, Luis José Catoggio¹, and Enrique Roberto Soriano¹. ¹Hospital Italiano De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina.

Objectives: Cardiac valve involvement in patients with Systemic Sclerosis (SSc) is uncommon, except for tricuspid regurgitation associated with pulmonary hypertension, and data regarding its frequency is inconsistent. Our objective was to estimate the incidence rate of moderate to severe valvular disease in patients with SSc compared with controls.

Methods: We included patients with SSc diagnosis (ACR 2013 criteria) belonging to our health management organization (HMO) and followed by our unit from January 1^st 2000 to December 31th 2017. Each patient with SSc was matched by age and sex with 3 to 4 controls of our HMO with at least 1 cardiac ultrasound performed during the study period. Subjects were followed until: a) their death, b) the end of the study, c) they voluntarily left the HMO. Electronic medical records were reviewed, demographic and disease characteristics were collected, and incidence rates of valve involvement were calculated for each valve (moderate/severe valvular disease, valve calcification and valve sclerosis) and compared between SSc and controls.

Results: 127 patients with SSc (108 with limited and 18 with diffuse SSc; 96.1% females; 18.4% Scl-70 positive and 67.2% anti centromere positive) and 497 controls were included. Patients with SSC has a significantly higher incidence of aortic stenosis (1.1 vs 0.3 per 100 patients-year, p < 0.001), mitral regurgitation (1.9 vs 0.9 per 100 patients-year, p = 0.001) and tricuspid regurgitation (1.9 vs 0.4 per 100 patients-year, p < 0.001) than controls. Valvular surgery was significantly more frequent in SSc than controls (0.4 vs 0.1 per 100 patients-year, p = 0.03). Aortic sclerosis (6.7 per 100 patients-year), aortic calcification (2.1 per 100 patients-year), mitral sclerosis (2.3 per 100 patients-year) and mitral calcification (2.9 per 100 patients-year) were also more frequent in SSc patients than controls (p < 0.05 for all comparisons).

Conclusions: We found significant higher incidence rates of aortic stenosis, mitral regurgitation and tricuspid regurgitation in SSc patients compared to their matched controls. Patients with SSc also required more valvular surgery. Moreover, aortic and mitral valves sclerosis and calcification were found more often in SSc patients’ echocardiographies than in controls.

173

RITUXIMAB IN PATIENTS WITH AUTOIMMUNE DISEASE AND ACTIVE TUBERCULOSIS

Hugo Javier Madariaga Charaja¹, Maria Elena Luza¹, Valery Ascuña¹, Carola Cervera¹, and Brissette Soto. ¹Hospital III Yanahuara Essalud Arequipa Perú.

Objectives: To present safety and efficacy of the concomitant use of Rituximab in patients with autoimmune disease being treated for active tuberculosis (TB)

Methods: We included all patients with active TB and concomitant autoimmune disease treated with Rituximab over the last 5 years, treated in hospital III Yanahuara, Arequipa- Perú.

Results: Five patients with active tuberculosis as well as autoimmune disease were treated with Rituximab at a dose of 1 g, 2 doses with an interval of 15 days every 6 months. 4 Female and 1 male. Median age of 41.6 years. Two with ANCA-associated vasculitis, two with systemic lupus erythematosus and one with rheumatoid arthritis. The most frequent symptoms were fever 60%, cough 60%, dyspnea 40% and thoracic pain 40%. Pulmonary TB was confirmed in 3 patients (BK +), renal TB in 1 patient (BK + in urine) and miliary TB (BK -, miliar type intertitial infiltrate and fever).

Autoimmune disease remained inactive in 100% of patients who received antituberculous treatment associated with the use of rituximab and were cured of active TB infection. There were no adverse events of either treatment.

Conclusions: - Rituximab is apparently effective and safe in patients with active TB associated with rheumatological diseases.

- It could be the treatment of choice in patients with a high risk of TB or a high prevalence of TB.

181

PREVALENCE OF NEUROPSYCHIATRIC SYNDROMES IN A GROUP OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN QUITO-ECUADOR

Heidi Fernandez¹, Andrea Cevallos¹, Fernando Naranjo-Saltos¹, Ruth Jimbo Sotomayor², Diego Mera², Efrain Basantes¹, Gabriela Carolina Guevara¹, Gina Carrillo¹, Alejandra Chacón¹, Janeth Diaz¹, and Carla Hurtado¹. ¹Hospital Eugenio Espejo, Quito, Ecuador, ²Pontificia Universidad Católica del Ecuador, Quito, Ecuador.

Objectives: Determine the prevalence of neuropsychiatric syndromes in a group of patients with systemic lupus erythematosus (SLE) in a hospital in Quito-Ecuador.

Methods: A descriptive, cross sectional study was conducted in 85 patients with SLE in a hospital in Quito-Ecuador. Neuropsychiatric syndromes were evaluated through the use of the MINI International Neuropsychiatric Interview and the Montreal scale. Data were grouped into the 4 most prevalent neuropsychiatric syndromes in patients with SLE according to literature (cognitive impairment, anxiety and mood disorders, and psychosis). There is a known association between the presence of SLE neuropsychiatric manifestations with the antiphospholipid syndrome (APS) and corticosteroid use. A bivariate analysis was used to study the association between these variables.

Results: 85 patients, with an average age of 34.12 ± 11.5 years were included, of which 94% were female. 71% of participants (60 patients) had at least one neuropsychiatric syndrome. The most frequent was cognitive impairment (n = 43, 51%) followed by anxiety disorders (n = 35, 41%), mood disorders (n = 34, 40%) and psychosis (n = 1; 1%). 38% presented mild cognitive impairment and 13% had moderate impairment. No severe cognitive disorders were reported in this study. 38% of participants met criteria for the antiphospholipid (APL) syndrome, and of them, 66% had a neuropsychiatric syndrome (OR = 1.83, p = 0.2). The majority of the patients (n = 84; 99%) were treated with corticosteroids during the study; of them, 59 patients presented neuropsychiatric syndromes (OR = 0.9, p = 0.8). Neither association was statistically significant.

Conclusions: There was a high prevalence of neuropsychiatric syndromes in this cohort of patients. The most prevalent was cognitive impairment, followed by anxiety and mood disorders, similar to other international investigations. The results of this study denote the need to create multidisciplinary units that include rheumatologists, internists, psychiatrists and psychologists for the timely detection and treatment of these manifestations. Additional studies are required to establish risk factors for the development of these syndromes and to evaluate associations with specific APL antibodies.

28

IN THE 21ST CENTURY: IS STILL RHEUMATOID ARTHRITIS A RISK FACTOR FOR OSTEOPOROTIC FRACTURES?

Florencia Pierini¹, Marina Scolnik¹, Valeria Scaglioni¹, Javier Rosa¹, and Enrique R. Soriano¹. ¹Hospital Italiano De Buenos Aires, Caba, Argentina.

Objectives: To compare the incidence of osteoporotic fractures in RA patients diagnosed after the year 2000 with matched controls from a university hospital-based health management organization (HMO).

Methods: Consecutive RA patients (n=100) diagnosed after the year 2000 (all fulfilling criteria ACR/EULAR 2010 of AR), from the HMO, were matched (age and sex) with controls (1:2). The follow-up period began at the index date, defined as the date of RA diagnosis for RA patients and the date of the first medical claim at the HMO for the non-RA patients. Subjects were then followed until they voluntarily left the HMO, a fracture occurred, the end of study (May 1st, 2018), or death. Electronic medical records were reviewed and demographic, clinical and treatment data were collected. Incidence rates per 1000 persons-years (PY) of distinct types of fractures after index dates were calculated and compared between groups. A multivariate Cox regression analysis was performed to identify factors associated with fractures.

Results: No difference was found in the overall fracture incidence rate per 1000 PY between RA and controls (19.5, CI 12.7-28.6 vs 12.1, CI 7.7-18.7, p=0.07). In the Cox regression analysis, only age (HR 1.06, 1.02-1.11, p=0.006) and a prior fracture (HR 9.85, 2.97-32.64, p <0.001) were associated with fractures after the index date. Neither a diagnosis of RA (HR 0.86, CI 0.24-3.07, p 0.81) nor a prolonged use (>3 months) of low dose corticosteroids (HR 1.57, CI 0.39-6.23, p 0.52) were associated with increased fracture risk. When analyzing each type of fracture, only vertebral fractures were more common in RA patients compared to controls (12.9 per 1000 PY, CI 8.9-25.8, versus 3.4, CI 1.4-8.1, p=0.01, respectively) but vertebral fractures were not associated with the prolonged use of low dose corticosteroids (HR 3.43, CI 0.74-15.82, p=0.11).

Conclusions: In this cohort of RA patients diagnosed after the year 2000, no overall increased risk of fractures was found in comparison to matched controls. This may be due to a better disease control and to the rational use of corticosteroids.

50

POSTRAUMATIC STRESS DISORDER IN PATIENTS WITH RHEUMATOID ARTHRITIS

Marisel Vanesa Bejarano¹, Anastasia Secco¹, Marta Mamani¹, Romanini Felix¹, Natalia Tamborenea¹, and Nicolas Lloves Schenone¹. ¹Hospital Bernardino Rivadavia, CABA, Argentina.

Objectives: To estimate the frequency of traumatic events prior to the diagnosis of RA. To determine the frequency of PTSD in patients with traumatic events prior to the diagnosis of RA. To compare demographic, clinical, serological characteristics, existence of depression and anxiety, according to the presence or absence of PTSD.

Methods: Methods: Observational, analytical, cross-sectional study. Patients with a diagnosis of RA were included according to the ACR Criteria (1987) and ACR EULAR (2010). Patients with another rheumatic or chronic autoimmune disease were excluded. To determine the presence of PTSD, the Traumatic Experiences Questionnaire was used in its Spanish-validated version. To assess the severity of PTSD, the Davidson Trauma Scale was used in its Spanish version. The continuous variables were described as mean and standard deviation (SD) or median and interquartile range (IQR), according to distribution and sample size. The categorical variables were expressed in percentages. For the bivariate analysis of continuous variables we used the Student t or Mann Whitney test, according to the distribution and sample size. For the categorical variables we used Chi square or Fisher's exact test, according to the expected frequency distribution. A logistic regression model was performed taking PTSD as a dependent variable.

Results: 128 patients were included, 86.72% were female, with a mean age of 52.23 years (± 12.39). 55.47% of patients reported at least 1 traumatic event prior to the diagnosis of RA. The most frequently reported traumatic event was the unexpected death of a family member or close friend (39, 50%). 32.39% of the patients who had experienced a traumatic event presented PTSD. 43.48% of patients with PTSD experienced a severe disorder. 63.49% of the patients had some degree of depression and 55.56% of anxiety.

Statistically significant differences were found between the patients who presented PTSD vs those without PTSD in: female sex (100% vs 83.81%, p = 0.04), anxiety (median 12, IQR: 4-18 vs 6, IQR: 0-11 p <0.01) depression (median 14, IQR: 6-19 vs 6 IQR: 0-12 p <0.01).

The main variable that showed an independent association with PTSD was depression (OR: 1.13, 95% CI: 1.05-1.20, p <0.01).

Conclusions: We observed that more than half of patients had experienced at least 1 traumatic event prior to the diagnosis of RA and 32.39% of them presented PTSD.

PTSD was found associated with the female sex, the presence of anxiety and, independently, depression. However, we found no association with the activity or the severity of the disease.

A possible explanation for these findings could be that disease´s characteristics are the result of various factors, with stress being one more determinant, within many existing ones.

59

TOLERANCE, SURVIVAL, AND ADHERENCE TO METHOTREXATE TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS

Juan Manuel Sevillano Gutierrez¹, Dafne Capelusnik¹, Emilce Schneeberger¹, and Gustavo Citera¹. ¹Instituto de Rehabilitación Psicofísica (IREP), CABA, Argentina.

Objectives: To evaluate the survival of MTX treatment, the frequency of adverse events, causes of discontinuation and adherence in patients with RA.

Methods: Consecutive patients 18 years and older with a diagnosis of RA (ACR / EULAR 2010 criteria), who had begun treatment with MTX during their disease were included. Sociodemographic, clinical and therapeutic data were collected by review of the clinical history and personal interviews of patients. Date of initiation and discontinuation of MTX, route of administration, concomitant treatments and consumption of coffee and tobacco were recorded. We analyzed the presence of adverse events (AE), their characteristics and the medical decision about MTX treatment. Adherence to treatment was evaluated using the Compliance Questionnaire Rheumatology questionnaire in its 5-item summary version (CQR5). Statistical Analysis: Descriptive statistics. Chi square test or Fisher's exact test; Student's T-test or Mann Whitney test and ANOVA. Survival of treatment by Kaplan-Meier and comparisons by log Rank. Multiple logistic regression, Cox regression. A p value <0.05 was considered significant.

Results: We included 118 patients, 101 were women (85.6%), with a median age (m) of 56 years (IQR 49-64) and a m disease duration of 10 years (IQR 6-18). Thirty-five patients (29.7%) were smokers and 56 patients (47.5%) consumed coffee. Eighty-five patients (72%) received MTX orally. The m dose of MTX was 15 mg weekly (IQR 15-23.75). 43.2% of patients presented AE associated with MTX, 20 of these patients (16.9%) had to discontinue MTX. Gastrointestinal intolerance was the most frequent AE (27.1%), followed by laboratory test disturbances (12.7%). Level of adherence to treatment was excellent, detecting that 86.6% of the patients presented an adherence ≥80%.

The median cumulative survival of MTX treatment was 348 months (95% CI: 235-460.9). In the univariate and multivariate analyzes, there was no association of survival of MTX with sociodemographic variables, disease characteristics, comorbidities, concomitant treatment, route of administration, coffee consumption nor level of adherence.

Conclusions: In our cohort, adherence and survival of MTX treatment were good. The accumulated survival was almost 30 years. Although there were AE recorded in more than a third of patients, its presence did not determine the discontinuation of treatment in most cases.

117

“LIVING WITH RHEUMATOID ARTHRITIS” IN AN INDIGENOUS QOM POPULATION OF ROSARIO, ARGENTINA: A COMMUNITY QUALITATIVE STUDY

Sofía Fernández², Rosana Maris Quintana^1,2, Stella Orzuza², Adriana MR Silvestre², Ana Bensi², Mario Goñi², Paola Iglesias², Nora Mathern², Vanina García-Bianco², Romina Nieto^1,2, Andrés Gil², Ana Bouza², Marcela Valdata², Bernardo Pons-Estel^1,2, and Ingris Pelaez-Ballestas^2,3. ¹Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR). Rosario, Rosario, Argentina, ²GLADERPO (Grupo Latinoamericano de Estudios de Enfermedades Reumáticas en Pueblos Originarios), Rosario, Argentina, ³Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México.

Objectives: To describe the experience of social suffering by the indigenous Qom community of patients with RA, and the illness trajectories along with their experience with the local health care system in the city of Rosario, Argentina.

Methods: Qualitative research focus on medical anthropology. Setting: Primary health care. Methodology: ethnographic method, with observations and indepth-interviews. Interviews were recorded and transcribed verbatim. The transcripts were analyzed using an ethnographic approach. A triangulation strategy was implemented for the analysis.

Results: A total of 33 interviews were conducted in 29 individuals with RA. The analysis revealed: 1. “normalization” of their symptoms and of their limitations in performing daily tasks.; 2. The individuals’ relationship with the local health care system was complex and limited in several aspects (e.g. access to health care, continuity of treatment) and; 3. The complexity of help-care seeking process and lack of cultural competence.

Conclusions: RA is a disease that has a negative impact on the daily lives of the Qom people living in Rosario. Improving the relationship between this population and the local health care system as well as the implementation of a RA multidisciplinary approach that takes into account the population cultural sensiivity needs to be a priority.

275

QUALITY OF LIFE IN COLOMBIAN PATIENTS WITH RHEUMATOID ARTHRITIS. A DESCRIPTIVE STUDY

Pedro Santos-Moreno¹, Fernando Rodriguez¹, Laura Villarreal-Peralta¹, and Diana Buitrago-Garcia². ¹Biomab -Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES- Investigación y educación en salud, Bogotá, Colombia.

Objectives: Rheumatic and musculoskeletal conditions are a diverse group of diseases that are usually caused by problems of the immune system, inflammation, gradual deterioration of joints, muscles and bones. Rheumatoid arthritis (RA)is considered the most common condition among them; the disease is chronic and might get worse over time. RA is typically painful and limits function causing a major impact on the patients’ quality of life. The objective of this study was to evaluate the quality of life patients with RA using the Quality of life in Rheumatoid Arthritis (RAQol) questionnaire in a specialized RA center in Bogotá, Colombia in 2018.

Methods: We performed a descriptive study, we collected sociodemographic data, the Spanish version of the RAQol was applied; this scale has a score from 1 to 10 where 10 is associated with better quality of life. We excluded patients with psychological or psychiatric disorders. Descriptive epidemiology was performed for each variable’ we performed a comparison of means regarding age and RAQol score.

Results: We interviewed 310 patients. 92% were female and 8% male. Mean age was 60 years, SD 10.5. The average time from diagnosis was 14 years. SD 11. The mean score for the scale was 6.8 ± 1.7. When we evaluated each RAQoL instrument domain. the domain with the highest score was the support from family and friends 7.8 ± 2, follwoed by family interaction and mood. We found a positive association (p<0.05) between age and RAQol score.

Conclusions: Our study showed that our patients have an overall good quality of life. As research has shown (2, 3) the domain related to family and friends support had higher scores and the lowest are related to pain and arthritis. Thus, it is important to develop and to provide multidisciplinary programs in order to improve the patient´s quality of life. On the other hand, further research is needed in order to explore outcomes associated with a better or worse quality of life.

27

IMPACT OF PSORIATIC ARTHRITIS FROM THE PATIENT’S PERSPECTIVE IN THE CONTEXT OF THE PSORIATIC ARTHRITIS IMPACT OF DISEASE (PSAID) QUESTIONNAIRE: AN ONLINE GLOBAL SURVEY

Laura Coates¹, Ana-Maria Orbai², Valderilio Azevedo³, Joseph C. Cappelleri⁴, Jade Moser⁵, Ralph Lippe⁶, Lihi Eder⁷, Pascal Richette⁸, Meng-Yu Weng⁹, Ruben Queiro Silva¹⁰, and Lara Fallon¹¹. ¹University of Oxford, Oxford, United Kingdom, ²Johns Hopkins University School of Medicine, Baltimore, USA, ³Universidade Federal do Paraná, Curitiba, Brazil, ⁴Pfizer Inc, Groton, USA, ⁵The Harris Poll, Rochester, USA, ⁶Pfizer Pharma GmbH, Berlin, Germany, ⁷Women's College Research Institute, University of Toronto, Toronto, Canada, ⁸Lariboisière Hospital, Lariboisière, University of Paris 7, Paris, France, ⁹Department of Internal Medicine, Division of Allergy, Immunology and Rheumatology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan, ¹⁰Rheumatology Division, HUCA, Oviedo, España, ¹¹Pfizer Inc, Montreal, Canada.

Objectives: Psoriatic arthritis (PsA) is a complex disease with high impact on health-related quality of life (HRQoL). The PsA core domain set¹ includes pain, patient global assessment, physical function, HRQoL, and fatigue. To evaluate the impact of PsA on health domains, a global survey was developed; we report the results in the context of the PsA Impact of Disease (PsAID) questionnaire due to its high content validity for patients. ²

Methods: A patient-based survey was conducted online from Nov 2, 2017 to Mar 12, 2018. Eligible patients (≥18 years of age) had PsA for >1 year, had visited a rheumatologist/dermatologist in the past 12 months, and had reported using ≥1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported current symptoms and impact of PsA on daily life. Post-survey, responses were aligned with PsAID health domains. Analyses included descriptive statistics and binomial tests.

Results: 1286 patients/8 countries participated; 84% reported moderate/severe PsA. Social and work PsA impacts were reported by 84% and 81% patients, 56% stopped sports/recreational activities, 42% reported decreased work productivity. Commonly reported major/moderate PsA impacts were on: physical activity (78%), ability to perform activities (76%), emotional/mental well-being (69%). More patients in Brazil, France, Spain, UK reported negative impact on emotional well-being, compared with Australia, Canada, Taiwan (p<0.05). Social impacts included emotional distress (58%), social shame/disapproval (32%), ceased participation in social activities (45%). Most respondents (62%) reported major/moderate impact on work productivity. More patients in Brazil, France, USA reported negative impact on work productivity, compared with Canada, Spain, Taiwan (p<0.05). 97% patients reported musculoskeletal symptoms in the past year: joint pain (79%), tenderness (60%), swelling (60%), stiffness (57%), inflammatory back pain (IBP; 53%). Joint pain (32%) and IBP (12%) were considered the most bothersome; 53% patients taking prescription medication reported joint pain.

Conclusions: All health domains that patients reported on were impacted by PsA in this survey, aligning with the life impact domains of the patient-derived PsAID questionnaire. Most patients reported an impact of PsA on aspects of their social, work, and physical life. These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during the shared decision-making processes between healthcare professionals and patients. References: 1. Orbai AM et al. Ann Rheum Dis 2017; 76: 673–80.

2. Gossec L et al. Ann Rheum Dis 2014; 73: 1012–9.

100

EFFECTIVENESS AND SAFETY OF INFLIXIMAB, GOLIMUMAB AND USTEKINUMAB IN PSORIATIC ARTHRITIS FROM A LONGITUDINAL OBSERVATIONAL REGISTRY

Proton Rahman¹, Regan Arendse², Isabelle Fortin³, Andrew Chow⁴, Majed Khraishi⁵, Suneil Kapur⁶, Michel Zummer⁷, Raheem Kherani⁸, Emmanouil Rampakakis⁹, Odalis Asin-Milan¹⁰, Allen J. Lehman¹⁰, and Francois Nantel¹⁰. ¹Memorial University, St John's, Canada, ²University of Saskatchewan, Saskatoon, Canada, ³Centre de Rhumatologie De l’Est du Quebec, Rimouski, Canada, ⁴Credit Valley Rheumatology, Missisauga, Canada, ⁵Nexus Clinical Research, St John's, Canada, ⁶Private practce, Ottawa, Canada, ⁷Hopital Maisonneuve-Rosemont, Montreal, Canada, ⁸University of British Columbia, Vancouver, Canada, ⁹JSS Medical Research, Montreal, Canada, ¹⁰Janssen Inc., Toronto, Canada.

Objectives: To describe the profile of psoriatic arthritis (PsA) patients selected for treatment with infliximab (IFX), golimumab (GLM) or ustekinumab (UST) treatment in Canadian routine care and to describe the long-term real-world effectiveness and safety of these agents.

Methods: 462 PsA patients treated with IFX, GLM or UST were enrolled into the Biologic Treatment Registry Across Canada (BioTRAC) registry between 2006-2015, 2010-2017 and 2014-2017, respectively. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed with changes in TJC28, SJC28, skin, enthesitis, dactylitis, pain, HAQ, acute phase reactants. Safety was evaluated with the incidence of adverse events (AEs) and drug survival rates.

Of the 111 IFX-, 281 GLM- and 70 UST-treated patients, the proportion of males were 52.3%, 46.3% and 37.1%, the mean age was 48.4, 52.8 and 53.1 years and the mean disease duration was 5.8, 6.1 and 5.7 years, respectively. Most patients were bio-naive (85.6%, 77.9% and 55.7% for IFX, GLM and UST, respectively (p<0.001). UST-treated patients had lower baseline DAS28 CRP (3.4 vs 3.9; p=0.0031), SJC (3.8 vs 5.3; p=0.0046) and higher PASI (4.8 vs 2.2; p=0.0061) compared to patients treated with GLM.

Results: Treatment with IFX, GLM and UST was associated with significant improvements in all disease parameters over time (p<0.001), respectively with similar efficacy between agents. The only exception was the proportion of patients in minimal disease activity at 12, 24 and 36 months which reached 40.7%, 50.0% and 55% in IFX-patients; 64.7%, 68.8% and 78.9% in GLM-patients and 58.8%, 60.0% and 83.3% in UST-patients (p=0.004 and p<0.001 vs IFX).

AEs were reported for 74.8%, 69.8% and 52.9% (138, 114 and 115 events/100 PYs) and SAEs for 19.8%, 8.5% and 5.7% (8.8, 19.6 and 28.6 events/100 PYs) covering 325, 567 and 87 years of exposure for IFX-, GLM- and UST-treated patients, respectively. One, one and no deaths occurred IFX-, GLM- and UST-treated patients, respectively. The proportion of patients who discontinued treatment were 63.1%, 50.9% and 50.0% over a mean exposure of 2.9, 1.9 and 1.2 years to IFX, GLM and UST, respectively.

Conclusions: Differences in baseline characteristics between patients treated with an anti-TNF over an anti-IL12/23 agent suggest that the level of joint to skin involvement might be driving physician choice when the time comes to choose a biologic agent. IFX, GLM and UST treatment significantly reduced disease activity and improved functionality in a similar fashion and were well tolerated in patients with PsA.

176

SUBCUTANEOUS SECUKINUMAB PROVIDES SUSTAINED INHIBITION OF RADIOGRAPHIC PROGRESSION IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: 52-WEEK RESULTS FROM A PHASE 3 STUDY

Philip Mease¹, Désirée van der Heijde², Robert Landewé³, Shephard Mpofu⁴, Proton Rahman⁵, Hasan Tahir⁶, Atul Singhal⁷, Elke Böttcher⁸, Sandra Navarra⁹, Xuan Zhu¹⁰, Aimee Readie¹⁰, Ken Abrams¹⁰, and Luminita Pricop¹⁰. ¹Swedish Medical Center and University of Washington, Seattle, United States, ²Leiden University Medical Centre, Leiden, Netherlands, ³University of Amsterdam, Amsterdam, Netherlands, ⁴Novartis Pharma AG, Basel, Switzerland, ⁵Memorial University of Newfoundland and Labrador, St. John's, Canada, ⁶Whipps Cross University Hospital, Barts Health NHS Trust,United Kingdom, ⁷Southwest Rheumatology, Dallas, United States, ⁸Rheumazentrum Favoriten, Vienna, Austria, ⁹University of Santo Tomas Hospital, Philippines, ¹⁰Novartis Pharmaceuticals Corporation, East Hanover, United States.

Objectives: Secukinumab (SEC), a fully human anti-interleukin-17A mAb, significantly improved signs and symptoms and inhibited radiographic progression versus placebo (PBO) at Week (Wk) 24 in patients (pts) with psoriatic arthritis (PsA) in the FUTURE 5 study. ¹ Here, we report the effects of SEC on radiographic progression, additional efficacy endpoints and safety through 52 wks.

Methods: Pts (N=996) with active PsA, were randomized (2:2:2:3) to subcutaneous (sc) SEC 300mg with loading dosage (LD; n=222), 150mg with LD (n=220), 150mg without LD (n=222), or PBO (n=332). All groups received SEC or PBO at baseline (BL), Wks 1, 2, 3, and 4, and then every 4 wks. At Wk 16, PBO non-responders were switched to SEC 300mg or 150mg; remaining PBO pts were switched at Wk 24. Radiographic progression was assessed by mean change in van der Heijde-modified total Sharp score for PsA (mTSS). Pts were stratified based on anti-TNF status (naïve/inadequate response [IR]). Additionally, radiographic data were analyzed by linear mixed effects model (random slope) at Wk 24 and 52. Efficacy assessments at Wk 52 included ACR20/50, PASI75 and resolution of dactylitis and enthesitis. Safety analyses included all pts who received ≥1 dose of SEC.

Results: 91.9% (204/222; 300mg LD), 91.4% (201/220; 150mg LD) and 86.9% (193/222; 150mg No LD) pts completed 52 wks of treatment. Inhibition of radiographic progression was sustained through 52 Wks. Proportions of pts with no radiographic progression (change from BL in mTSS ≤0.5) with SEC at 52 Wks were 92% (300 mg LD), 85% (150 mg LD), and 87% (150 mg No LD). Mean changes from baseline in mTSS by linear mixed effects model at Wk 24 were 0.03 (P<0.01), 0.14 (P<0.05) and -0.10 (P<0.001) respectively, vs. 0.51 (PBO). Corresponding mean change at Wk 52, was -0.18 (300mg LD), 0.11 (150mg LD) and -0.20 (150mg no LD). ACR20/50 responses at Wk 52 were, 68.9/46.8, 64.1/41.4 and 65.8/43.2 in the 300mg LD, 150mg LD and 150mg no LD groups, respectively. Other clinical responses were sustained or improved through 52 wks. No new or unexpected safety signals were identified.

Conclusions: Secukinumab provided sustained inhibition of radiographic progression through 52 wks. Clinical responses were also sustained through 52 wks. The safety profile was consistent with that previously reported. ¹

References: 1. Ann Rheum Dis. 2018;77:890-897.

185

USTEKINUMAB AND TNF INHIBITORS IMPROVE JOINT INFLAMMATION IN PSORIATIC ARTHRITIS SIMILARLY: FIRST FOLLOW-UP DATA FROM A ROUTINE CARE STUDY IN 8 EUROPEAN COUNTRIES (PsABio)

J. Smolen¹, P. Bergmans², I. Bondareva³, K. de Vlam⁴, E. Gremese⁵, B. Joven-Ibáñez⁶, T.V. Korotaeva⁷, M.T. Nurmohamed^8,9, P.P. Sfikakis¹⁰, S. Siebert¹¹, P. Smirnov¹², E. Theander¹³, G. Valentini¹⁴, and L. Gossec^15,16. ¹Medical University of Vienna, Vienna, Austria, ²Biometrics, Janssen-Cilag B.V., Breda, Netherlands, ³Kemerovo Regional Clinical Hospital, Kemerovo, Russia, ⁴University Hospitals Leuven, Leuven, Belgium, ⁵Fondazione Policlinico Universitario Gemelli - Università Cattolica del Sacro Cuore, Rome, italy, ⁶Hospital Universitario 12 de Octubre, Madrid, España, ⁷Nasonova Rheumatology Research Institute, Moscow, Russia, ⁸VU University Medical Centre, Amsterdam, Netherlands, ⁹Amsterdam Rheumatology and Immunology CVU University Medical Centre, Amsterdam, Netherlands, ¹⁰1st Dept. of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Athens University, Athens, Greece, ¹¹Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom, ¹²Biometrics, Janssen-Cilag B.V., Moscow, Russia, ¹³Biometrics, Janssen-Cilag B.V., Solna, Sweden, ¹⁴Università della Campania “Luigi Vanvitelli”, Naples, Italy, ¹⁵Hôpital Pitié Salpêtrière, Paris, France, ¹⁶Sorbonne Université, Paris, France.

Objectives: The purpose of PsABio (ClinicalTrials.gov ID: NCT02627768) is to evaluate the persistence, therapy regimens, efficacy and tolerability of 1st, 2nd and 3rd-line biological disease-modifying antirheumatic drugs (bDMARDs) – tumor necrosis factor inhibitors (TNFi) and ustekinumab (UST) – in psoriatic arthritis (PsA). Here we present first follow-up data on joint-related outcomes.

Methods: Of 278 UST-treated and 285 TNFi-treated patients, enrolled up to August 2017, 152 and 151 patients respectively had reached the 6-month follow-up while remaining on the initial treatment line. We present joint-related outcomes as observed data, comparing baseline to follow-up within the cohorts. As baseline characteristics show differences in factors potentially influencing treatment effects, after full enrollment, between-group comparisons were adjusted using propensity score analysis.

Results: Of 303 patients: mean (SD) age=49.7 (12.8) years; disease duration=7.2 (8.2) years; 50.5% female. At 6 months’ follow-up, 7.6% UST-treated and 10.2% TNFi-treated patients stopped/switched bDMARD. Line of treatment differed (UST: 40%, 36%, 24%; TNFi: 64%, 29%, 7.3% for 1st, 2nd, 3rd-line respectively). Prevalence of concomitant sDMARD differed (UST: 40% [29% MTX]; TNFi: 54% [40% MTX]). DAS-28 improved significantly from baseline, UST: 4.3 (SD 1.2), TNFi: 4.3 (SD 1.3) by mean (95%CI) -1.3 (-1.6, -1.0) and -1.3 (-1.5, -1.2). Significant improvements seen in both cohorts across all treatment lines and PsA subtypes (data not shown). CDAI also significantly improved, by mean (95%CI) -10.9 (-13.1, -8.6) and -10.8 (-12.6, -9.0) in UST and TNFi cohorts: 14% and 15.5% reaching CDAI remission. For DAPSA, statistically significant improvements, mean (95%CI) UST: -18.4 (-22.2, -14.5) and TNFi: -19.5 (-22.5, -16.5). cDAPSA also significantly improved in both cohorts: mean (95%CI) -15.6 (-18.6, -12.5) and -16.9 (-19.4, -14.4) for UST and TNFi, respectively.

Conclusions: Both UST-treated and TNFi-treated patients showed statistically significant and considerable improvements in joint-related measures after 6 months in a real-world setting, irrespective of line of treatment and subtype of psoriatic disease.

323

EFFICACY AND SAFETY OF INTRAVENOUS GOLIMUMAB IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS: RESULTS FROM A PHASE 3 OPEN-LABEL STUDY

Alberto Spindler¹, Nicola Ruperto², Cesar Francisco Pacheco Tena³, Ingrid Louw⁴, Gabriel Vega-Cornejo⁵, Daniel Kingsbury⁶, Michael Clark⁷, Karen Bensley⁷, Xiaoming Li⁷, and Hermine Brunner⁸. ¹Centro Médico Privado de Reumatología, San Miguel de Tucuman, Argentina, ²Istituto Giannina Gaslini, Pediatria II, Reumatologia, PRINTO Coordinating Centre, Genoa, Italy, ³Universidad Autónoma de Chihuahua, Circuito Universitario Campus II, Chihuahua, Mexico, ⁴Panorama Medical Centre, Cape Town, South Africa, ⁵Hospital México Americano, Guadalajara, Mexico, ⁶Randall Children's Hospital at Legacy Emanuel, Portland, United States, ⁷Janssen Research & Development, LLC, Spring House, United States, ⁸Cincinnati Children’s Hospital Medical Center, Cincinnati, United States.

Objectives: To assess efficacy & safety of intravenous golimumab in pediatric patients with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy through 28 weeks of treatment.

Methods: A multicenter, Phase 3, single arm, open-label trial was conducted using intravenous golimumab at a dose of 80mg/m² given at weeks 0 & 4, then every 8 weeks thereafter, in pediatric patients ages 2-17 years of age with active polyarticular course juvenile idiopathic arthritis despite methotrexate therapy. Patients received commercial MTX weekly at same BSA-based dose as at time of study entry. All the results below are based on full analysis set which includes all patients who received at least 1 dose of study agent.

Results: 180 patients were screened (130 enrolled,127 treated) with the first patient screened on 22Dec2014; last patient first treated 26Dec2017, & last patient’s Wk28 visit was 09Jul2018.

Proportion of JIA ACR 30,50,70, & 90 responders at Wk28 was 83.5%,79.5%,70.1%, & 46.5%, respectively. 29.1% of patients met criteria for inactive disease at Wk28. Median change from baseline for JASDAS 10, 27, & 71 was -14.20, -16.60, & -20.32, respectively at Wk28. JADAS 10, 27, & 71 minimal disease activity was met by 15% of patients at Wk28.

Proportion of patients experiencing at least 1 treatment-emergent AE through Wk28 was 77.2%. MedDRA system organ class with highest incidence of AEs was Infections & infestations (57.5%); most commonly reported AE upper respiratory tract infection (17.3%), then nasopharyngitis (15.0%). Six patients experienced serious AEs through Wk28: Herpes zoster disseminated, Infective exacerbation of bronchiectasis, Sepsis, Varicella, Mycosis fungoides, & Suicidal ideation. These events resulted in permanent discontinuation of intravenous golimumab, except for Varicella.

Conclusions: Intravenous golimumab delivered at a dose of 80mg/m2 at weeks 0 & 4, then every 8 weeks thereafter appears to be effective in these patients with a safety profile similar to other TNF inhibitor therapies.

326

DERMATOLOGIC AUTOIMMUNE DISEASES AND POLYAUTOIMMUNITY IN JUVENILE COLOMBIAN PATIENTS

Clara Malagón¹, Maria del Pilar Gómez¹, Catalina Mosquera¹, Camilo Vargas¹, Tatiana González¹, Cristine Arango¹, Lorena Martin¹, and Pilar Pérez¹. ¹Universidad El Bosque, Bogotá, Colombia.

Objectives: Organ specific and systemic autoimmune diseases (AD) share several pathogenic mechanisms and clinical features that may predispose the co-occurrence of more than one AD within an individual. Polyautoimmunity has been documented on adult and juvenile patients. Multiple autoimmune syndrome is the association of three or more AD. From a registry of 317 patients followed at 15 pediatric rheumatology clinics, 6 patients developed one or more dermatologic AD during the follow up.

Methods: According to diagnostic criteria and/or skin biopsy the AD was classified. As index disease was the first diagnosed AD. If the diagnosis was confirmed with an interval less than six months they were classified as simultaneous if this period was longer. The clinical, serologic and the types of associations were determined.

Results: Vitíligo, Localized scleroderma, Urticaria Vasculitis, psoriasis and additional lupus were identified as skin AD. Female predominance and wide range of age of onset were observed in all of them. They were the index AD disease, second, third or even fourth AD. As index disease Vitiligo was the most common dermatological AD (n= 17/ 317), followed by localized scleroderma (9/317), discoid lupus (5/317) urticaria vasculitis (5/317) psoriasis (2/317) and alopecia universalis (2/317). Multiple associations of AD were documented during follow up. Well recognized associations were identified but unusual clusters were also confirmed. The most common associations were: Vitíligo and Hashimoto, Sclerodermia and Vitíligo but associations with systemic AD were also frenquent. Patients that developed MAS developed one or two skin AD at any time of the follow up and one boy developed scleroderma, psoriasis and vitiligo sequentially but not any systemic AD.

Conclusions: Dermatological ADs may precede, coincide or follow addional organ specific and systemic AD and become as component of SAM. Patients with these diseases should be followed because of the risk of additional organ specific and systemic AD. A variable but significant percentage of cases developed MAS. Changes in the clinical course and/or serologic profile must alert the clinician about polyautoimmunity.

6

A PROOF-OF-CONCEPT, PHASE 2 CLINICAL TRIAL OF THE GI SAFETY OF AN HYDROGEN SULFIDE-RELEASING ANTI-INFLAMMATORY DRUG (ATB-346)

John Wallace¹, Andre Buret¹, David Vaughan², Marcelo Muscara⁴, Gilberto De Nucci⁵, Peter Nagy. ¹University of Calgary, Calgary, Canada, ²University of Calgary, Calgary, Canada, ³Antibe Therapeutics Inc., Toronto, Canada, ⁴University of Sao Paolo, Sao Paulo, Brazil, ⁵University of Campinas, Campinas, Brazil, ⁶National Institute of Oncology, Budapest, Hungary.

Objectives: Hydrogen sulfide (H₂S) is a naturally occurring gaseous mediator produced by various eukaryotic cells and by intestinal bacteria. It can exert cytoprotective and analgesic effects. ATB-346 is an H₂S-releasing derivative of naproxen that was found to be more potent and long-acting than naproxen. In animal studies, ATB-346 produced negligible gastrointestinal (GI) damage and bleeding, despite profound inhibition of cyclo-oxygenase (COX). A human efficacy study demonstrated that ATB-346 (250 mg daily) was very effective in reducing pain in patients with osteoarthritis of the knee, and inhibiting COX activity. This study tested the hypothesis that ATB-346 is GI safer than naproxen.

Methods: This was a double-blind, active control study. 244 healthy volunteers completed the study. Upper GI endoscopy was performed prior to and on day 14 after commencing treatment with naproxen (550 mg twice daily) or ATB-346 (250 mg once daily in the morning and placebo once daily in the evening). Whole blood thromboxane synthesis (COX activity) and plasma hydrogen sulfide levels were also measured.

Results: For the primary endpoint, incidence of ulcers ≥3 mm in diameter, 53 subjects (42%) taking naproxen developed at least one ulcer, while only 3 subjects taking ATB-346 developed at least one ulcer (p<0.00001). The two drugs produced comparable suppression of systemic COX activity. Subjects in the naproxen group developed more ulcers per subject (an average of 4) than in the ATB-346 group (1.3/subject), and a greater incidence of larger (≥5 mm diameter) ulcers (125 vs. 0), respectively. The incidence of abdominal pain, gastro-esophageal reflux and nausea were markedly lower with ATB-346 than with naproxen. Systemic COX activity was inhibited by 95% in both groups, and plasma H₂S levels were significantly elevated in subjects treated with ATB-346 (by ~50%; p<0.001).

Conclusions: As in pre-clinical studies, this phase 2 clinical trial demonstrated a dramatic increase in the GI safety of ATB-346 versus one of the most commonly used NSAIDs, naproxen. ATB-346 produced equivalent suppression of COX to naproxen, consistent with a previous Phase 2A clinical trial that demonstrated significant pain relief in patients with osteoarthritis of the knee. ATB-346 appear to be an effective and much safer alternative to existing NSAIDs.

91

EFFICACY AND SAFETY FROM A PHASE 2B TRIAL OF SM04690, A NOVEL, INTRA-ARTICULAR WNT PATHWAY INHIBITOR FOR THE TREATMENT OF OSTEOARTHRITIS OF THE KNEE

Yusuf Yazici¹, Timothy McAlindon², Allan Gibofsky³, Nancy Lane⁴, Christian Latterman⁵, Nebojsa Skrepnik⁶, Chris Swearingen¹, Anita DiFrancesco¹, Jeyanesh Tambiah¹, Marc Hochberg⁷, and Mirta Grifman¹. ¹Samumed, LLC, San Diego, United States, ²Tufts Medical Center, Boston, United States, ³Weill Cornell Medical College and Hospital for Special Surgery, New York, United States, ⁴UC Davis Medical Center, Davis, United States, ⁵Brigham and Women’s Hospital, Cambridge, United States, ⁶Tucson Orthopedic Institute, Tucson, United States, ⁷University of Maryland School of Medicine, Baltimore, United States.

Objectives: A phase 2a study of SM04690, a small-molecule, intra-articular (IA) Wnt pathway inhibitor reduced knee pain and improved physical function and medial joint space width (mJSW) at 52 weeks in subgroups of subjects with unilateral symptomatic knee osteoarthritis (OA) compared to placebo (PBO).¹

A 24-week phase 2b study was conducted to refine patient reported outcome (PRO) measures, target population, medication dose, and to evaluate safety. PRO results for Weeks 12 and 24 are presented here.

Methods: Study subject inclusion criteria required ACR-defined knee OA, Kellgren-Lawrence (KL) grade 2 or 3, and Pain Numeric Rating Scale (NRS) scores ≥4 and ≤8 in the target knee and <4 in the contralateral knee. A single IA injection of 2 mL SM04690 (0.03, 0.07, 0.15, or 0.23 mg), vehicle PBO, or sham (dry needle only) was given in the target knee at baseline. PRO endpoints included change from baseline in weekly average of daily pain in the target knee by NRS diary (NRS) [0-10], Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain [0-100], WOMAC Physical Function [0-100], and Patient Global Assessment (PTGA) [0-100]. Differences between active treatment groups and vehicle PBO were analyzed with baseline-adjusted analysis of covariance (ANCOVA).

Results: 695 subjects (mean age 59.0 [±8.5] years, BMI 29.0 [±4.0] kg/m2, female 58.4%, KL3 57.3%) were enrolled and dosed; 635 subjects (91.4%) completed the study. No meaningful differences in the incidence of adverse events were observed between treatment and control groups.

In the Full Analysis Set, significant improvements from baseline compared to vehicle PBO were observed in pain NRS for 0.07 mg (Week 12 [P=0.001], Week 24 [P=0.031]) and 0.23 mg (Week 12 [P=0.012], Week 24 [P=0.022]) SM04690 dose groups. Similar improvements were observed in WOMAC Pain for 0.07 mg (Week 12 [P=0.04]) and 0.23 mg (Week 12 [P=0.003], Week 24 [P=0.031]) dose groups. For WOMAC Physical Function, improvements were observed for 0.07 mg (Week 12 [p=0.021]) and 0.23 mg (Week 12 [p=0.006], Week 24 [P=0.017]) dose groups. PTGA improvements were observed for 0.07 mg (Week 12 [P=0.031]) and 0.23 mg (Week 12 [P=0.010], Week 24 [P=0.033]) dose groups.

Conclusions: SM04690, in development as a potential disease-modifying OA drug, showed in this Phase 2b study statistically significant improvements from baseline in both the 0.07 mg and 0.23 mg dose groups compared to vehicle PBO for Pain NRS, WOMAC Pain, WOMAC Physical Function, and PTGA. These data support the continued development of SM04690 as a treatment for knee OA. Phase 3 studies are being planned.

References 1. Yazici Y, et al. Arthritis Rheumatol. 2017; 69 (suppl 10).

46

GIANT CELL ARTERITIS. TREATMENT WITH TOCILIZUMAB

Vicente Aldasoro Cáceres¹, Javier Mendizábal Mateos¹, Sara García Pérez¹, Inmaculada Paniagua Zudaire¹, Concepción Fito Manteca¹, Loreto Horcada Rubio¹, Natividad Del Val Del Amo¹, Ricardo Gutiérrez Polo¹, Laura Garrido Courel¹, Juliana Restrepo Vélez¹, Rosario Ibáñez Bosch¹, and Eduardo Loza Cortina¹. ¹Complejo Hospitalario De Navarra, Pamplona, España.

Objectives: Tocilizumab (TCZ) has shown efficacy in clinical trials and in real-world data on giant cell arteritis (GCA). We describe our experience with TCZ in GCA in those patients with inefficacy to previous therapies in a tertiary hospital.

Methods: Search and review clinical data of patients diagnosed with GCA and treated with TCZ in the last 5 years.

Results: 23 patients (3 men); mean age 71.5 (7.8). 57% positive temporal artery biopsy. 74% received treatment with sDMARD. 26% started TCZ in combination with methotrexate. Before TCZ was started, the median methotrexate and steroids doses were 20 mg (10-23.75) and 12.5 mg (5-30), respectively. 5 patients had visual lost: 2 amaurosis and 3 optic neuritis.

TCZ was started after a median time from GCA diagnosis of 12 months (2-21). Symptoms in all patients but one improved totally or partially; their CRP an ESR decreased to normal levels at month 1 (p<0.0001). 11/15 patients were asymptomatic at one year. 74% TCZ intravenously. We did not find different efficacy related to the administration route. 3 patients stopped TCZ: respiratory infection, lost of efficacy and hypertransaminasemia at 24, 18 and 2 months, respectively.

8 patients developed toxicity to steroids: 3 diabetes, 3 behavior alterations and 2 myopathies. Most relevant adverse side-effect was serious infections observed in 6/23.

Conclusions: In our series TCZ was effective, fast and safe treatment in the management of GCA refractory to other treatments.

55

ASSESSMENT OF THE IMPACT OF CAPILLAROSCOPY TRAINING TO NON-EXPERT PROFESSIONALS AND ITS CORRELATION WITH EXPERT PROFESSIONALS IN NORTHWESTERN COLOMBIA, 2017

Miguel Antonio Mesa Navas^1,2, Andrea Restrepo Acosta², Carlos Jaime Velásquez Franco^1,2, Libia Maria Rodriguez Padilla², and Laura Escobar². ¹Clínica Universitaria Bolivariana, Medellín, Colombia, ²Escuela de Ciencias de la Salud, Universidad Pontificia Bolivariana, Medellín, Colombia.

Objectives: To evaluate the impact of a capillaroscopy training on non-expert professionals and its correlation with experience capillaroscopists in Medellín Colombia, 2017.

Methods: This study was quasi-experimental in its design and included individuals older than 18 who were medics or medical students and gave consent. Participants received a 30-minute introduction and were evaluated (time 1) with a test in which 60 photos were displayed for 30 seconds each. Participants were asked to assess the shape, size and general pattern of nail fold capillaries (20 photos in each section). Subsequently, a six-hour training was carried out, and a new evaluation was performed (time 2) with the same images as in time 1 but in a different order. The agreement among experts was considered the gold standard. The concordance between the experts (inter-reader, intra-reader) and the agreement of each participant with the expert at the two times were evaluated by the Kappa coefficient. The results obtained between the two times were compared using the Wilcoxon test.

Results: 56 medical professionals and two experts were included. The inter-reader and intra-reader agreement between the experts were substantial (Kappa between 0.61-0.80) and almost perfect (Kappa between 0.81-1.00), respectively. After the training, a significant increase was observed both in the number and in the percentage of correct answers with respect to the consensus of experts (p <0.001). The kappa coefficient for time 1 was: 0.50 (CI 0.33-0.71) for form, 0.76 (CI 0.53-0.79) for size, 0.45 (CI 0.29-0.57) for general pattern and 0.71 (CI 0.59-0.84) recognizing specifically scleroderma pattern. At time 2 the kappa was 0,80 (CI 0,60-0,90) for form, 0,76 (CI 0,55-0,80) for size, 0,64 (CI 0,46-0,79) for general pattern and 1 (CI: 1-1) for normal pattern vs systemic sclerosis.

Conclusions: A short Nailfold videocapillaroscopy training can improve the ability of non-expert personnel to identify capillaroscopic abnormalities. This is particularly important when recognizing the scleroderma pattern where the agreement with the gold standard was perfect.

POSTERS

1. BASIC SCIENCE

304

URIC ACID TRANSPORTER GENE POLYMORPHISMS AS A GOUT SUSCEPTIBILITY MARKER IN A MEXICAN POPULATION

Denise Clavijo Cornejo¹, Aiana Francisco-Balderas², Alberto A. López-Reyes¹, Jose Peralta-Aguilar³, Javier Fernández Torres¹, Yessica Zamudio-Cuevas¹, Luis Silveira-Torre⁴, Janitzia Vazquez-Mellado⁵, and Gabriela Angelica Martínez-Nava¹. ¹Instituto Nacional De Rehabilitación, Ciudad de México, México, ²Instituto Politecnico Nacional, Ciudad de México, Mexico, ³Universidad de la Salle, Ciudad de México, México, ⁴Instituto Nacional de Cardiología, Ciudad de México, México, ⁵Hospital General de México Eduardo Liceaga, Ciudad de México, México.

Objectives: Gout is caused by the deposition of monosodium urate crystals mainly in joints; in Mexico, the prevalence of gout is estimated at 0.3% but real data are still unknown. Gout is a disabling chronic disease resulting from a high serum uric acid (UA) levels. It is known that renal urate excretion is involved in the development of the disease; studies at the genetic level have shown that single nucleotide polymorphisms (SNP) are related with gout. The aim of this study was to analyze the association between the SNPs of uric acid transporters’ genes and gout susceptibility in Mexican subjects.

Methods: 62 patients with gout (ACR/EULAR criteria), and 165 healthy subjects age ≥18 years old were included. Eight SNP of seven different genes and 11 ancestry-informative markers were genotyped using TaqMan probes in a Quant Studio 12kFlex instrument. The allelic discrimination and ancestry analysis were carried out using the TaqMan genotyper and STRUCTURE1.2.1 software, respectively. For the associations between the genetic variants and gout the odds ratios (ORs) with 95% confidence intervals were calculated by multinomial logistic regression models.

Results: The ABCG2 rs2231142 (T allele) and BCAS3 rs2079742 (C allele) minor alleles were associated positively with gout (OR=3.48, p<0.01 and OR= 3.02, p<0.01; respectively). On the other hand, a significantly lower risk for gout was found in the carriers of the minor allele of ATXN2 rs653178 (C allele OR=0.44 p=0.047) and SFMBT1 rs6770152 (G allele OR=0.42 p<0.01) polymorphisms. Notwithstanding we did not observe a significant association between gout diagnosis and the minor allele of GCKR (rs780094 and rs1260326), OVOL (rs642803) and PRKG2 (rs10033237) polymorphisms; these showed a significant association with the disease when analyzed by genotype in a co-dominant inheritance model.

Conclusions: In a Mexican population, the prevalence and incidence of gout is underestimated; the disease may be chronic and disabling. It is necessary to carry out studies in order to identify the genetic susceptibility to the disease. This preliminary study suggest that the SNPs present in the uric acid transporters can be used as susceptibility markers in Mexican population; however, we are aware that larger sample size studies are required. Financed by FOSSIS-2016; Project-273143.

2. LUPUS AND OTHER SYSTEMIC AUTOIMMUNE DISORDERS20

PULMONARY FUNCTION, IL-1BETA, IL-18, TGFBETA-1 AND SCD163 IN PATIENTS WITH INTERSTITIAL LUNG DISEASE POSITIVE TO ANTI SYNTHETASE AUTOANTIBODIES AFTER TREATMENT WITH METHOTREXATE, LEFLUNOMIDE AND PREDNISONE

Jorge Rojas-Serrano¹, José Guillermo Mejía-Hurtado¹, Montserrat Ixchel González-Perez¹, Enrique Ambrocio-Ortiz², Ramcés Falfán-Valencia², Gloria Pérez-Rubio², Heidegger Mateos-Toledo¹, Mayra Mejia¹, and Ivette Buendía-Roldán³. ¹Unidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional De Enfermedades Respiratorias. Ismael Cosio Villegas, Ciudad De México, México, ²Laboratorio HLA, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México, México, ³Laboratorio de Investigación Traslacional en Envejecimiento y Fibrosis Pulmonar, Instituto Nacional de Enfermedaedes Respiratorias, Ismael Cosío Villegas, Ciudad de México, México.

Objectives: The association of antisynthetase antibodies (ASAB) with either interstitial lung disease (ILD) and/or inflammatory myopathy (IM) is known as antisynthetase syndrome (ASSD). ILD is the most serious manifestation of ASSD with high morbidity and mortality. We performed this study to estimate levels of serum of IL-18, IL-1β and sCD163, before and after treatment with methotrexate, leflunomide and prednisone in patients with ASSD.

Methods: Patients with ILD all positive to ASAB. All patients were treated at a single center with methotrexate, leflunomide and prednisone. We examined the clinical course, pulmonary function tests, pattern of interstitial lung disease by HRCT, and baseline levels and at follow up of IL-18, IL-1β, TGFβ-1 and sCD163 by ELISA.

Results: 40 patients were included. Most patients were Jo1 positive (45%), other ASAB 55%. Eighty percent of the patients had improvement in pulmonary disease at follow up (improvement in FVC > 10% of predicted and/or improvement in DCLO > 15% of predicted). IL-1β, IL-18 and sCD163 had a decrease in levels at follow up (12 months): baseline IL-1β 46 (31-91) pg/ml Vs follow up IL-1β 21 (15- 30) pg/ml, p < 0.0001; baseline IL-18 158 (74-324) pg/ml Vs. follow up IL-18 77 (41-120) pg/ml, p < 0.0001; baseline sCD163 67182 ± 38548 pg/ml, Vs. follow up sCD163 31020 ± 16142 pg/ml, p < 0.0001. On the contrary, levels of TGFβ-1 increased after at follow up: baseline TGFβ-1 56 (52-61) pg/ml, Vs. follow up 65 (60-69) pg/ml, p < 0.001. Patients with lung disease progression (n:5) had a tendency towards higher levels of sCD163 at baseline (p=0.09) and both at follow up (p=0.07).

Conclusions: These results suggest, that after treatment there is a decrease in the levels of pro inflammatory cytokines (IL-1β and IL-18), with an increase in regulatory TGFβ-1. There was a tendency towards higher levels of sCD163 in patients with progressive lung disease, both at baseline and at follow up, so it may be a biomarker of bad prognosis in patients with ILD positive to ASAB.

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RELATIONSHIP BETWEEN NAILFOLD CAPILLAROSCOPY PATTERNS AND MODIFIED MEDSGER SEVERITY SCALE IN SYSTEMIC SCLEROSIS

Diana Paola Wilches Reyes¹, Mario Javier Moreno Álvarez¹, and Rafael Ignacio López Martínez¹. ¹Hospital Luis Vernaza, Guayaquil, Ecuador.

Objectives: 1.- To determine the relationship between nailfold capillaroscopy patterns (NFC) and modified Medsger severity scale (MSS) in patients with Systemic Sclerosis (SSc). 2.- To identify the relationship between SSc and NFC specific autoantibodies. 3.- To link together the MSS and the years of evolution of the disease. 4.- To determine the relationship between modified Rodnan skin score (mRSS) with NFC.

Methods: Observational, analytical, descriptive, cross-sectional study in adult patients with SSc seen at Luis Vernaza outpatient Clinic from December 2017 to May 2018. The capillary alterations were correlated with MSS. The data was analyzed by MedCalc Statical Software 18.2.1 version.

Results: 49 patients were studied, 38 with limited SSc (77.55%) and 11 with diffuse SSc (22.44%), average age was 49,5 years; 91.8% were women. Patients with late NFC had greater systemic involvement (P=0.0444), Spearman 0.30 rho coefficient. There was no association between the different NFC and auto autoantibodies specific to SSc (p= 0.6045). There was no evidence of correlation between years of evolution of the disease and MSS, Kendall´s Tau 0.66 (95% CI 0.124-0.258; p=0.4918). In evaluating the correlation between MSS score and NFC, this was found to be significant (p=0.0490).

Conclusions: There is a strong relationship between NFC and the severity of visceral damage in patients with SSc. The severity of the disease is not influenced by the years of evolution or by the presence of autoantibodies. Cutaneous involvement seems to accompany the microangiopathic changes evaluated by capillaroscopy. The periodic evaluation of NFC in autoimmune rheumatic diseases and in particular in SSc, is a tool of great diagnostic and prognostic value.

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ASSOCIATION OF C3 AND C4 HYPOCOMPLEMENTEMIA WITH CLINICAL MANIFESTATIONS, DISEASE ACTIVITY, AND DAMAGE ACCRUAL IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME

Patricia Jordan-Gonzalez¹, Ricardo Gago-Piñero¹, Irma Vázquez-Sanabria¹, Noemi Varela-Rosario¹, Naydi Perez-Rios¹, and Luis Vila¹. ¹University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.

Objectives: C3 and C4 hypocomplementemia are predictors of lymphoma in patients with primary Sjögren's syndrome (pSS). Also, some studies have shown associations with disease damage. However, the association with clinical manifestations and other comorbidities is not well established. Therefore, we determined the clinical correlates of C3 and C4 hypocomplementemia in a group of patients with pSS.

Methods: A cross-sectional study was performed in Hispanics from Puerto Rico with pSS. All patients were ≥ 21 years of age and met the 2012 American College of Rheumatology Classification Criteria for pSS. Demographic features, health-related behaviors, clinical manifestations, autoantibodies, comorbidities, pharmacologic treatment, disease activity (per EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]), and disease damage (per Sjögren’s Syndrome Disease Damage Index [SSDDI]) were determined. Serum C3 and C4 levels were measured by immunoturbidimetry at pSS diagnosis. The association of C3 or C4 hypocomplementemia with these factors was studied using bivariate and multivariate logistic regression analyses adjusted for age, sex, and disease duration.

Results: A total of 94 patients were studied, 93.6% were woman. The mean (SD) age and disease duration were 52.4(12.4) and 5.9(4.8) years, respectively. Low C3 and C4 levels were observed in 9.6% and 13.8% patients, respectively. Seven (7.4%) patients had both C3 and C4 hypocomplementemia. Patients with C3 hypocomplementemia were more likely to have leukocytoclastic vasculitis (44.4% vs. 8.2%, p=0.010), interstitial lung disease (33.3% vs. 1.2%, p=0.002), asthma (33.3% vs. 7.1%, p=0.039), and higher SSDDI scores (2.2±2.2 vs. 0.5±0.9, p=0.002) than those with normal C3. Except for asthma, all variables retained significance in the multivariate analysis. Patients with low C4 were more likely to have leukocytoclastic vasculitis (38.5% vs. 7.4%, p=0.007), interstitial lung disease (23.1% vs. 1.2%, p=0.008), and higher ESSDAI (1.5±1.7 vs. 0.6±0.8, p=0.013) and SSDDI (2.00±2.20 vs. 0.48±0.76, p=0.003) scores than those with normal C4. In the multivariate analysis, only interstitial lung disease and disease damage retained significance.

Conclusions: In this population of patients with pSS, C3 and C4 hypocomplementemia were associated with interstitial lung disease and damage accrual. In addition, low C3 levels were associated with leukocytoclastic vasculitis. These data suggest that complements C3 and C4 have clinical and prognostic value in pSS patients.

31

VITAMIN D CUT-OFF POINTS AND THEIR RELATIONSHIP WITH CLINICAL FEATURES IN PATIENTS WITH ACTIVE LUPUS OR LUPUS NEPHRITIS

Renato Guzman¹, Luis Gabriel Piñeros¹, Aníbal A. Teherán¹, María Camila Mejía Guatibonza^1,2, Luis Miguel Pombo¹, and Vanessa Cadavid^1,2. ¹Fundación Universitaria Juan N. Corpas, Bogotá, Colombia, ²Hospital Universitario Clínica San Rafael, Bogotá, Colombia.

Objectives: Vitamin D (25OHD) has immunomodulatory properties that can play a major role in patients with active lupus or lupus nephritis. Vitamin D’s immunomodulatory function could be influenced by demographic factors, comorbidities (Charlson score), bone supplements, and other features. The aim of our study was to determine the association between the best 25(OH)D cut-off points and specific clinical factors present in patients with active lupus or lupus nephritis.

Methods: A descriptive study using available clinical records of patients diagnosed with systemic lupus erythematosus, being followed at two rheumatology clinics was performed. A tree decision model was used to identify the best cut-off points of 25(OH)D [ng/mL] and clinical features associated with active lupus (SLEDAI-2k >6) or lupus nephritis.

Results: We identified 81 patients, median age 41 years, women 91.3%. Active lupus and lupus nephritis were present in 69.1% and 29.6% of these patients, respectively. Median 25(OH)D was 26.49 ng/mL, without a difference when patients with active and non-active lupus were compared, but lower in lupus nephritis patients 21.50 ng/mL (p=0.015). Lupus nephritis was absent in patients with 25(OH)D cut-off points >38.8 (alone) or ≤38.8 if they were older than 57 years. Lupus was active in patients younger than 44 years with low comorbidity plus cut-off point 25(OH)D >35 and in patients older than 44 years with TSH > 2,11 lU/mL and without Vitamin D suplement (Fig. 1).

Conclusions: Both the activity of the disease and lupus nephritis is influenced by vitamin D levels in interaction with other factors such as age, TSH, comorbidities and the substitution of Vitamin D.

32

LOW DISEASE ACTIVITY STATE (LDAS) PREDICTS A BETTER HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS

Manuel F. Ugarte-Gil^1,2, Rocío Gamboa-Cárdenas², Cristina Reátegui-Sokolova^2,3, Mariela Medina-Chinchón², Francisco Zevallos², Claudia Elera-Fitzcarrald^1,2, Victor Pimentel-Quiroz², Jorge M. Cucho-Venegas², César Pastor-Asurza^2,4, Zoila Rodríguez-Bellido^2,4, Graciela S. Alarcón^5,6, and Risto Perich-Campos^2,4. ¹Universidad Científica Del Sur, Perú, ²Hospital Guillermo Almenara Irigoyen. EsSalud, Perú, ³Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Perú, ⁴Universidad Nacional Mayor de San Marcos, Perú, ⁵University of Alabama at Birmingham, USA, ⁶Universidad Peruana Cayetano Heredia, Lima, Perú.

Objectives: To determine if achieving LDAS predicts a better HRQoL.

Methods: SLE patients from a single center cohort with at least two visits were included. Visits were performed every six months. HRQoL was measured with the LupusQoL, disease activity with the SLEDAI-2K, damage with the SLICC/ACR damage index (SDI) and comorbidities with the Charlson Comorbidity Index (CCI). LDAS was defined as a SLEDAI-2K≤4, prednisone daily dose ≤7.5mg/d and immunosuppressive drugs on maintenance dose; patients on remission were also included in this group. Generalized estimating equations were performed, using as outcome each one of the eight components of the LupusQoL in the subsequent visit, and the activity state in the previous visit; as possible confounders, we included disease duration, SDI, CCI, antimalarial use on each visit and age at diagnosis, gender, socioeconomic status and the same component of the LupusQoL at the baseline visit.

Results: Two hundred and forty-three patients were included, 225 (92.6%) were female, mean age at diagnosis was 35.44 (SD: 13.13) years. Patients had a mean of 3.94 (1.98) visits for a total of 958 visits. During the follow-up, 590 (61.6%) visits were categorized as LDAS. LDAS predicted a better HRQoL in the components of physical health [B: 4.17 (95%CI: 1.20; 7.14); p=0.006], pain [B: 6.47 (95%CI: 3.18; 9.76); p<0.001], planning [B: 4.97 (95%CI: 1.43; 8.52); p=0.006], burden to others [B: 4.12 (95%CI: 0.24; 8.01); p=0.037], emotional health [B: 4.50 (95%CI: 1.56; 7.44); p=0.003] and fatigue [B: 3.25 (95%CI: 0.04; 6.47); p=0.048].

Conclusions: Being on LDAS predicts a better HRQoL, especially in the components of physical health, pain, planning, burden to others, emotional health and fatigue.

33

TIME IN REMISSION AND LOW DISEASE ACTIVITY STATE (LDAS) ARE ASSOCIATED WITH A BETTER QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: DATA FROM A MULTI-ETHNIC, MULTICENTER US COHORT

Manuel F. Ugarte-Gil^1,2, Guillermo Pons-Estel³, Luis M. Vila⁴, Gerald McGwin Jr⁵, and Graciela S. Alarcón^5,6. ¹Universidad Científica Del Sur, Perú, ²Hospital Guillermo Almenara Irigoyen, EsSalud, Perú, ³Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Argentina, ⁴The University of Puerto Rico Medical Sciences Campus, San Juan, United States, ⁵The University of Alabama at Birmingham, United States, ⁶Universidad Peruana Cayetano Heredia, Lima, Perú.

Objectives: To determine whether the proportion of time patients achieve either Remission or LDAS is associated with a better QoL.

Methods: SLE patients from a well-established multiethnic, multicenter US cohort were included. Remission and LDAS were defined as follows: Remission, SLAM score=0 and prednisone ≤5 mg/day and no immunosuppressants); LDAS not in remission, SLAM score ≤3, prednisone ≤7.5 mg/day, no immunosuppressants; the proportion of time patients were in these two states (combined) was the independent variable. The end-points were the physical and mental summary measures (PCS and MCS, respectively) and the individual subscales of the Short Form (SF)-36 at the last available visit. Linear regression was used to estimate the association between the proportion of follow-up time in remission and LDAS and the SF-36 measures with and without adjustment for the following baseline variables: age, gender, racial/ethnic group, education, poverty, social support, abnormal illness behaviors, fibromyalgia, disease activity, damage and the baseline scores of the corresponding SF-36 summary measures and subscales.

Results: Five-hundred and forty-two patients with complete data for the dependent, independent and confounding variables were included. These patients were predominantly women, and either of Caucasian, African American or Hispanic ancestry. Overall, the mean scores for the summary measures of the SF-36 were low (38.9 for the PCS and 43.4 for the MCS); for the individual subscales the scores varied between 40.4 for vitality and 65.4 for mental health. In the adjusted MV analysis, the percent of time on either Remission and LDAS was associated with better QoL after adjusting for potential confounders, for PCS the parameter estimate was 9.47 (p<0.0001), for MCS 5.89 (p=0.0027), and for each subscale the estimates ranged between 7.51 (p=0.0495) for mental health and 31.79 (p<0.0001) for role physical.

Conclusions: The percent of time lupus patients stay on Remission or LDAS is associated with a better QoL as measured by the summary measures and subscales of the SF-36.

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INCIDENCE AND PREVALENCE OF ANTIPHOSPHOLIPID SYNDROME IN A HEALTH MANAGEMENT ORGANIZATION (HMO) IN ARGENTINA

Aurelia Luissi¹, Marina Scolnik¹, and Enrique Roberto Soriano¹. ¹Hospital Italiano De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina.

Objectives: Antiphospholipid Syndrome (APS) is an unusual disease and there are scarce epidemiological data about it. Our objective was to assess the incidence and prevalence rates of APS using data from a tertiary university hospital-based health management organization (HMO) in Latin America.

Methods: Different methods were applied in order to identify possible APS cases: (a) patients with diagnosis of APS, recurrent abortions and/or fetal death in HMO electronic medical records, (b) patients with a Lupus anticoagulant, IgG/IgM anticardiolipin and/or IgG/IgM β2glicoprotein positive test in laboratory database, (c) patients included in the Institutional Registry of Thromboembolic Disease of our hospital. Electronic medical records of all cases retrieved by these ascertainment methods were reviewed and definite APS was diagnosed if the 2006 modified Sapporo Criteria were fulfilled. Global, age-specific, and sex-specific incidence and prevalence rates were calculated for members of the HMO. For the incidence study members with continuous affiliation ≥ 1 year from January 2000 to January 2015 were followed until he/she voluntarily left the HMO, APS was diagnosed, death, or study finalization. Prevalence was calculated on January 1^st, 2015.

Results: 53 incident cases of APS were identified during the study period. A total of 349,775 persons contributed a total of 2,073,438 person-years. Incidence rates are reported as cases per 100,000 person-years (py): APS overall incidence rate was 2.6 (CI 1.9-3.2); it was 2.9 (CI 2.0-3.9) and 2.0 (CI 1.1.-3.0) in women and men, respectively. In our population, age-specific incidence and prevalence rates in female patients peaked in the third decades of life and in male they peaked in the sixth decades. On January 1st, 2015, 55 APS prevalent cases were identified from a denominator population of 135,750 HMO members. Prevalence rate was 40.5 per 100,000 persons (CI 29.8-51.2).

Conclusions: Incidence and prevalence rates were similiar to figures from previous reports. Incidence and prevalence rates in women were higher in the young population, and they were associated with obstetric morbidity.

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A RARE CASE OF DISSECTING AORTIC ANEURYSM SURVIVING WITH THE CLINICAL TREATMENT OF SLE

Elisa Terezinha Hacbarth Freire Elisa¹, Danielle Angelieri¹, Leandro Parmigiani¹, Taciana Paula Sousa Stacchini¹, Themis Torres¹, Mônica Duarte Costa¹, and Paola Fernanda B Toth¹. ¹Hacbarth Freire Serviços Médicos Ltda, São Paulo, Brazil.

Objectives: Systemic lupus erythematosus (SLE) can affect any organ or system. The activity of the disease is variable, with periods of remission, sometimes long.

AORTITE (Aortitis)– inflammation of the aortic artery wall, with or without rupture of its fibers, has been documented in a few cases, being LUPUS an extremely rare cause of dissecting aneurysm.

We described the case of a patient with grade III aortic dissection, seen in our service and treated clinically, who presented exceptional and no previosly described response to the treatment with rituximab, surviving and having full functional recovery.

Methods: S.M.I.T, Asian-descend, female, 56 years. SLE diagnosed in 1997, immune, hematological, and articular involvement; treated with corticosteroirds (CS), azathioprine with long periods of remission. Stable until August 2017, when she developed a UTI and, after 48 hours, she presented necrosis of the distal phalanx of the 2 ° right finger. Complement consumption, high CRP and ESR, anti DNA +; Angio computerized tomography of the aorta and its branches showed mild ectasia of the pulmonary artery. Increase dose of CS and Azatiotioprina and Cilostazol were given with excellent response. On December 2017 the dose of CS were reduced and Cilostazol discontinued. Later this month patient presented to her primary provider with high intensity lumbar pain. FAN = 1/1280; CRP = 11.6; D dimer = > 10,000; C3 = 55; C4 = 8.4. Angio CT of aorta showed the presence of a thrombus that began in the the aorta’s arch extending inferiorly to the abdominal aorta, with the presence of ulcerated areas.

Results: IV methylprednisolone 1g, followed the next day by Rituximabe 1g IV. Maintained on CS 60mg/day, blood pressure and pain control. Fifteen days after presentation, repeated Angio CTshowed increased ulcerations close to the renal and common Iliac arteries and a positive aneurysmal image in the left iliac. The patient received a second dose of rituximabe 1g. She was discharged from the hospital 72horas after, asymptomatic. On March2018, new Angio CT of aorta showed reabsorption of the intramural hematoma, no ulcerated projections, no areas of stenosis and no atherosclerotic plaques. The patient is well, normotensive, CS have been reduced. After one year, the patient is without evidence of SLE activity, in good health and using low doses of CS. The Angio CT of the aorta performed one year later is normal.

Conclusions: The occurrence of a dissecting aortic aneurysm in patients with active SLE is extremely rare, having been 15 documented cases. The extensive dissection verified, the response obtained with the immunobiological medications used and the patient's survival without accumulation of damage, make this case unique/

53

ROLE OF PREGNANCY IN THE CLINICAL PICTURE OF SLE

Alberto Christian Ortiz¹, Xiomara Cornejo¹, Romina Calvo¹, Susana Roverano¹, and Sergio Paira¹. ¹Sección Reumatología Hospital JM Cullen, Santa Fe, Argentina.

Objectives: To evaluate SLE activity during pregnancy and postpartum, pregnancy outcomes and to measure pregnancy organic accrual damage in SLE patients.

Methods: We performed a review of the medical records of pregnant patients with a previous diagnosis of SLE (ACR Criteria1997), 16 years or older. We evaluated age of onset, clinical course (since the patient met SLE criteria), time of follow up (since 1st consultation until pregnancy), and clinical manifestations before, during pregnancy and puerperium. Disease activity was assessed using the SLE disease activity index (SLEDAI). Flare was defined as SLEDAI ≥ 3. Damage accrual was measured with the SLICC/ACR Damage Index (SDI) (according to Gladman et al.), before and after pregnancy. Descriptive statistics: X² test, Fisher’s exact test and Student’s t test were used. Statistical significance was set at p<0.05.

Results: Data of 63 pregnancies from 47 patients were seen between 1997 to 2018. Average age at pregnancy: 27 years (SD:6). Abnormal obstetrical outcome: 25 incidents in 21 pregnancies out of 63 pregnancies reviewed (premature deliveries: 6, threatened abortion: 5, abortions: 4, congenital malformations: 4, low birth weight: 5, fetal demise: 1. Neither a clinical nor a laboratory variable was noted to have the ability to predict any impact on pregnancies’ outcome. In 35% of the pregnancies a flare was reported before pregnancy, 11% during the 1st trimester, 12% during the second trimester, 22% during the 3rd trimester and 14% after delivery. There was no relationship between SLE activity before and during pregnancy (p=0.58). There was an association between SLE activity during pregnancy and low C3 and C4 levels (p=:0.011 and p=0.004). Damage accrual occurred in 40 pregnancies, observing in only 2 of them after pregnancy.

Conclusions: SLE activity during and after pregnancy have no relationship with activity before pregnancy but low complement levels have influence in activity during pregnancy. We did not observe that pregnancy influenced organ damage in patients with SLE. The rate of obstetric complications was lower than described in the literature; we did not find any variables that could impact on them.

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MULTITARGET THERAPY IN PATIENTS WITH LUPUS NEPHRITIS: A TWO YEAR FOLLOW UP REPORT

Gisela E. Casillas-Ramos¹, Lilia Andrade-Ortega¹, and Fedra Irazoque-Palazuelos¹. ¹Departamento de Reumatología, CMN 20 de Noviembre, ISSSTE, Ciudad de México, México.

Objectives: Lupus Nephritis (LN) is the most significant cause of morbimortality in patients with Systemic Lupus Erythematosus (SLE) even despite recommended treatments. Given the complex pathogenesis of LN, multitarget therapy (MTT) has a logical basis and has been suggested for those cases with bad prognosis or therapeutic failure, with encouraging results.

The objective of this work is to evaluate the response to MTT in LN patients with bad prognosis or failure to treatment during a 2-year period of follow up.

Methods: This work is an analysis of the renal response (using Spanish Guide criteria) and survival in the group of patients from our LN cohort that received MTT and had at least 24 months of follow up. Demographic aspects, characteristics of the disease, histopathological data, and therapeutic history previous to MTT were recorded and correlated with the response to treatment. Statistics analysis was done with SPSS 21.

Results: 20 patients with LN were included in the study, 4 patients (20%) received MTT because of bad prognosis factors since starting therapy, 12 (60%) because of renal relapse and 4 (20%) because of refractory course. After 6/24 months of MTT there was complete response in 25%/75% of the patients, partial response in 50%/15%, and no response in 10%/10%, respectively. Remission at 24 months was associated with baseline albuminuria <1 g/24h and with response at 6 months. No deaths were reported. None of the patients needed dialysis or kidney transplantation and there were only 3 cases with a serious infection in the 2 year follow up period.

Conclusions: In our study, MTT was effective on inducing total or partial renal response on those patients with failure to conventional treatments, without a significant increase in serious adverse events.

Even though our study is small and from the review of medical records its results are encouraging and highlight the need for controlled studies with a larger number of patients in order to corroborate the efficacy and safety of combined treatments. We consider that MTT is promising for refractory LN.

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PREVALENCE OF UNUSUAL MITOTIC PATTERNS OBSERVED IN THE SCREENING OF ANTINUCLEAR ANTIBODIES DETECTED IN A CLINICAL LABORATORY IN GUAYAQUIL, FROM JANUARY TO OCTOBER 2018

Karin Daniela Cepeda Armendariz¹, Elena Isabel Romero Cevallos¹, and Vicenta Teodora Cevallos Carofilis¹. ¹Laboratorio Interlab S.A., Guayaquil, Ecuador.

Objectives: To determine the prevalence of rare mitotic Anti-Nuclear Antibodies patterns seen in the reports of patients with suspected autoinmune disease or diseases.

Methods: This is an observational study of available data from January to October of 2018 from the Interlab Laboratory of Guayaquil. Data were collected from 6313 serological tests that detected ANA using the method of Indirect Immunofluorescence (IFI), using HEP 2 cells as a substrate. Variables such as sex, age and titer were analyzed. Data were prepared and analyzed by two laboratory professionals. From the 6313 tests, 961 were positive/.

Results: The total number of patients who were ANA positive was 961 (15.2%); of them only 27 (0.43%) were positive for mitotic patterns. Of these 27 patients 81.5% were female and 18.5% male, with ages between 7 and 87 years of age; the mean age for women was 47 years, and 20 years for men. The percentage of cases with dilutions equal or greater than 1: 160 was 95% in the numa-like pattern of 95% and centrosome in 50%.

Numa like: 22 cases

Centrosome: 4 cases

Spindle fibers: 1 case.

Conclusions: This study demonstrates that the prevalence of rare mitotic patterns is 0.43%, which is low. This prevalence is in accordance with other studies. The Numa-like pattern is the most common of the mitotic patterns and the one that included patients from all ages. The centrosome pattern was more common in adults in their middle age. This work could be the start for others aimed at correlating the clinical manifestations with rare ANA patterns, given that the titer and the pattern reflect the activity of the autoimmune process.

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COSMETIC CAMOUFLAGE IMPROVES QUALITY OF LIFE IN SYSTEMIC LUPUS PATIENTS PRESENTING SEQUELAE OF CUTANEOUS MANIFESTATIONS ON THEIR FACE

Fernando Afranio Palmeira Oliveira¹, Fabiana de Miranda Moura dos Santos¹, Maria Veloso Rocha Mameluque¹, Thiago Loredo e Silva¹, Clara Otoni Neves¹, Douglas Mansur Guerra¹, Maria Fernanda Botelho Teixeira¹, Claudia Lopes Santoro Neiva², Ana Flavia Madureira de Pádua Dias², Rosa Weiss Telles¹, and Cristina Costa Lanna¹. ¹Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil, ²Santa Casa de Belo Horizonte, Belo Horizonte, Brazil.

Objectives: To investigate the effect of cosmetic camouflage on the health-related quality of life (HRQoL) of systemic lupus erythematosus (SLE) women presenting sequelae of cutaneous manifestations on their face.

Methods: Randomized controlled clinical trial (Universal Trial Number: U1111-1210-2554e) of ambulatory SLE women according to ACR 1997 and/or SLICC 2012 criteria, aged over 18 years presenting sequelae of cutaneous lupus manifestations on their face. Exclusion criteria were: SLEDAI 2k-modified> 4, lack of understanding to questionnaires, psychological and/or psychiatric treatment initiation or modification during the study. A final sample of 43 patients was divided: group I (n=28) patients were trained for cosmetic camouflage use and were instructed to use it daily; and group II (control – n=15) patients did not use any camouflage. SLE Quality of Life (SLEQoL) and Dermatology Quality of Life Index (DLQI) questionnaires were applied to all patients at baseline (T0) and after 12 weeks (T1), higher scores meaning worse HRQoL. The primary end point was a change on HRQoL after camouflage cosmetic use. End points were investigated per-protocol analysis; a p value <0.05 was considered to be significant.

Results: Both groups were similar at baseline regarding age [group I:45.0 (37.3-55.7)years versus group II: 50.0(43.0-55.0)years, p=0.575], disease duration [group I: 17.5 (7.3-26.5) years versus group II: 15.0 (9.0-17.0) years, p=0.452] and SLEDAI-2km [group I: 0 (0-2) versus group II: 2 (0-2), p=0.301]. The DLQI and SLEQoL scores decreased in the cosmetic camouflage group from baseline: DLQI [T0: 8.5 (4.0-16.0) versus T1: 3.0 (1.0-7.5), p=0.008]; SLEQOL [T0: 118.0 (91.0-154.3) versus T1: 95.5 (76.0-135.0), p=0.003]; while there was no variation in the control group. The variation difference of HRQoL scores between groups I and II was statistically significant: ΔDLQI [group I: -3.0 (-10.8-0.0) versus group II: 1.0 (-1.0-6.0), p=0.003] and ΔSLEQoL [group I: -14.5 (-33.0-0.0) versus group II:3.0 (-8.0-10.0), p=0.009]. The SLEQoL score variations were on physical function (p=0.033), humor (p = 0.033) and self-image (p=0.031) domains.

Conclusions: In this group of SLE women with low systemic disease activity and sequelae of cutaneous manifestations, we observed an improvement of HRQoL after daily use of cosmetic camouflage.

67

PREDICTORS OF ADVANCED CHRONIC KIDNEY DISEASE IN PATIENTS WITH ANCA VASCULITIS AND RENAL INVOLVEMENT

Gelsomina Alle¹, John F. Jaramillo Gallego¹, Marina Scolnik¹, Valeria Scaglioni¹, Carlos F. Varela¹, Gustavo Greloni¹, and Enrique Soriano¹. ¹Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.

Objectives: The aim of this study was to evaluate the predictors of advanced chronic kidney disease (ACKD) in patients with Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and renal involvement.

Methods: We included all patients with biopsy-proven ANCA glomerulonephritis (GN) between 2002 and 2016. Serum creatinine estimated glomerular filtration rate (eGFR), proteinuria, hematuria, renal histopathology and autoantibodies were recorded at diagnosis, at the end of induction treatment, after one year of treatment and at the end of follow-up, as well as treatments received, requirement of dialysis and renal or extrarenal relapses. Renal biopsies were reviewed and classified according to the classification proposed in 2010 for ANCA GN. Univariate analysis were performed to identify factors associated with long-term ACKD (eGFR <30 ml/min, stages 4 or 5 of KDIGO classification). The diagnostic accuracy for ACKD of each predictor variable were compared using areas under the curve (AUC) of ROC (receiver operating characteristic) curves.

Results: Sixty patients (76.7% women) were included: 17 GPA, 14 MPA, 5 EGPA, 24 RLV; with a mean age of 67.8 years (SD 13.1). Median follow-up time was 4.2 years (IQR 2.2-6.8). At the end of follow-up, 12 patients (20.7%) had an eGFR<30ml/min. In the univariate analysis the serum creatinine at diagnosis (OR 1.24, 95%CI 1.02-1.52, p0.03), end of induction (OR 15.4, 95%CI 2.41-98.28, p0.004), and 12 months (OR 19.25, 95%CI 2.75-134.92, p0.003), and the sclerotic class biopsy (OR 7.17, 95%CI 1.34-38.31, p0.02), were significantly associated with ACKD. The best diagnostic accuracy in ROC curves was shown by serum creatinine at the end of induction (AUC 0.93, 95%CI 0.83-1.00) and at 12 months (AUC 0.94, 95%CI 0.85-1.00).

Conclusions: In this cohort of patients with ANCA vasculitis and renal involvement, serum creatinine at the end of the induction period and after 12 months of treatment were the best predictors of ACKD (eGFR <30ml/min) at the end of follow-up.

71

CLINICAL, SEROLOGIC, ORGAN DAMAGE ACCRUAL, DISEASE ACTIVITY AND MORTALITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: GENDER DIFFERENCES

Susana Roverano¹, Romina Calvo¹, Alberto Ortiz¹, Sergio Paira¹, Lucas Costa², and Elena Carrera². ¹Hospital José María Cullen, Santa Fe, Argentina, ²Unidad Bioestadística Aplicada, Univ. Nacional del Litoral- Fac. de Ciencias Médicas, Santa Fe, Argentina.

Objectives: The incidence of Systemic Lupus Erythematosus (SLE) in males ranges from 4 to 22%. The disease is more frequent in females than in males (9:1). Male SLE carries a worse prognosis.

Arthritis (53%), anti-ds-DNA antibodies (46%), serositis (34%) and malar rash (27%) are the most prevalent findings in males at the onset of SLE.

The aim of this study was to determine gender differences in our SLE patients.

Methods: Material and methods: observational and historically study carried on in a single center.

We included all patients with SLE ACR criteria 1984 and 1997, taking into account the following variables at first consultation: sex, age, time of evolution and of follow up, symptoms and laboratory data (Erythrosedimentation Rate, Hemolytic Anemia, Leukopenia, Lymphopenia, Thrombocytopenia, ANA (HeP-2), anti-ds-DNA antibody, low C3 and C4, anti-Ro, La, Sm, RNP, anticardiolipins and Lupus Anticoagulant). Outcomes of both groups (SLE female and SLE male) were compared.

Results: 267 females and 34 males were identified, with similar age at SLE onset (29 years old). Females had a longer time of follow up (5,87 vs. 3,14 years p=0,0001) and a longer time since the presentation of the first symptoms due to SLE until consultation (40 vs 14 months p=0,001) than males. Alopecia was more frequent in males than in females (47 vs 29,6% p=0,039) but malar rash (32 vs 64% p=0,0001) and anti-Ro Antibodies (17,6 vs 31,5% p=0,02) were less frequent.

There were no diferences between groups in terms of treatment received, SLICC-SDI, SLEDAI at 1st visit, mortality (13,5% females vs. 17.6% males) and outcomes.

Conclusions: Similarly, to the data for the GLADEL cohort, our male patients presented at the same age and the delay to diagnosis was shorter than in females. SLE male patients of both GLADEL and Taiwan cohorts showed renal involvement with low C3 and higher mortality than female patients, unlike our study that showed Alopecia to be more frequent in males but males had similar outcomes than the female patients. There was no statistical difference in mortality between both groups.

77

INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS. EPIMAR GROUP

Florencia Vivero¹, Federico Campins¹, Silvia Babini¹, Pablo Malfante¹, Diana Lancellotti¹, Esteban Gándara¹, Javier Sebastiani¹, Victoria Basso¹, Juan Ignacio Enghelmayer², Adrián Gaser³, Norma Naval⁴, Mariana Lagrutta⁵, Soledad Altube⁶, Viviana Moyano⁷, Mónica Sacnun⁸, Javier Abdala⁹, Hernan Basilo Vigil¹⁰, Lilian Capone¹¹, Carolina Isnardi¹², Adriana Robles¹³, Magdalena Romiti¹, Marina Oliver¹, and Mariela Bastita¹. ¹Hospital Privado De Comunidad, Mar Del Plata, Argentina, ²Hospital de Clínicas, Buenos Aires, Argentina, ³Instituto Diagnóstico Médico, Buenos Aires, Argentina, ⁴Hospital Ángel Padilla, San Miguel de Tucumán, Argentina, ⁵Hospital Centenario, Rosario, Argentina, ⁶Hospital Municipal, Chivilcoy, Argentina, ⁷Hospital Italiano, Córdoba, Argentina, ⁸Hospital Provincial, Rosario, Argentina, ⁹Hospital Central, Mendoza, Argentina, ¹⁰Hospital Tornú, Buenos Aires, Argentina, ¹¹Instituto Vaccarezza, Buenos Aires, Argentina, ¹²Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ¹³Hospital San Bernardo, Salta, Argentina.

Objectives: The aim of this study was to describe the demographic, serological, imaging, and lung functional features along with the treatments for patients with diffuse interstitial lung disease (ILD) associated with systemic lupus erythematosus (SLE).

Methods: Descriptive, multicenter study. Patients from the EPIMAR cohort were included. Participants were recruited at 25 centers from Argentina that provided multidisciplinary care for ILD patients. Patients evaluated between January 2015 and April 2018 and diagnosed with ILD defined by the presence of suggestive pulmonary images on high-resolution computed tomography (HRCT) (irregular inter or intralobular septal thickening, traction bronchiectasis, cystic and/or ground glass images) associated with SLE according to 1997 ACR criteria were included. Serological data and studies of respiratory function (spirometry and DLCO) were recorded. All the images were blindly evaluated by a diagnostic imaging specialist with practice in chest diseases who defined the tomographic pattern. Data on treatment schemes were recorded.

Results: Out of the 381 patients recruited in the EPIMAR cohort, 29 (7.6%) presented SLE; and 90% (26/29) were women. Age ranged from 29 to 80 years with an average of 53 years (SD 12). Autoantibody frequency was ANAs: 93% (27/29), anti-Ro/SSA: 58% (15/26), and anti-RNP: 35% (9/26). The tomographic patterns found were: non-specific interstitial pneumonia (NSIP): 28% (8/29), usual interstitial pneumonia (UIP): 24% (7/29), NSIP/organized pneumonia (OP) overlap: 10% (3/29). At the time of diagnosis, the percentage of forced vital capacity (% FVC) was 66% (SD 17.58) and DLCO was 56% (SD 19.83). Treatment data were obtained for 83% of patients (24/29). All patients received corticosteroids. The immunosuppressants used were: 38% cyclophosphamide (9/24), followed by 25% azathioprine (6/24), and 21% mycophenolate (5/24). Outcome data were obtained (% FVC at 6-12 months) in 50% of cases, with stability or improvement of lung function in 78% (11/14) of the treated patients.

Conclusions: To the best of our knowledge, this study recruited the largest number of lupus patients with ILD. SLE-associated ILD is less frequent than in other connective tissue diseases. This SLE association was primarily found in middle-aged, non-smoker women with a significant prevalence of anti-Ro/SSA and a lower frequency of ANAs, in line with the data reported in other series. Longitudinal studies should be conducted to validate these results.

79

CHARACTERIZATION OF PREGNANT WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND MATERNAL-FETAL OUTCOMES: AN OBSERVATIONAL STUDY

José Raúl Lambertino-Montaño², Carlos Jaime Velásquez-Franco^1,4, Jorge Hernán Gutiérrez-Marín^3,4, María Nazareth Campo-Campo^3,4, José Enrique Sanín-Blair^3,4, Raúl Alejandro García^3,4, Simón Hoyos-Patiño⁴, Sara Manuela Ocampo-Ramírez⁴, Lady Johanna Hernández Zapata^1,5, Libia María Rodríguez-Padilla⁴, and Miguel Antonio Mesa Navas^1,4. ¹Clínica Universitaria Bolivariana, Medellín, Colombia, ²Clínica SOMER, Rionegro, Colombia, ³Clínica Universitaria Bolivariana, Colombia, ⁴School of Health Sciences. Universidad Pontificia Bolivariana, Medellin, Colombia, ⁵Universidad de Antioquia, Medellin, Colombia.

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of reproductive age, being the coexistence of SLE and pregnancy a common situation. This condition, if it is not in remission prior to pregnancy, can become active in a serious way during pregnancy and the immediate postnatal period, increasing the risk of maternal and fetal complications. The objective of this survey was to evaluate the epidemiological, clinical and therapeutic features of pregnant women with SLE, as well as their obstetric outcomes.

Methods: A cohort of pregnant women with SLE from the Maternal and Fetal Medicine and Rheumatology Units in two high-complexity hospitals from Medellin, Colombia, between 2010 and 2015, was constituted and evaluated. Qualitative variables were expressed in absolute and relative frequencies, while quantitative ones with mean and standard deviation.

Results: Forty patients and 43 pregnancies were included, with an average age at diagnosis of SLE of 24 ± 7 years. Joint involvement was the most frequent clinical manifestation (n=32; 80%). Only 8/43 (18.6%) of lupus pregnancies were active at the beginning of gestation. The most frequent obstetric complication was preeclampsia (11/43; 25.6%). The most common fetal complication was preterm birth (8/43; 18.6%); in this scenario, anticardiolipin and anti-DNA antibodies were positive in 10/43 (23.3%) and 15/38 (39.5%) pregnancies, respectively. In 13/43 (31.7%) pregnancies, a relapse of SLE during the third trimester occurred; six of them (46.1%) were classified as severe, mainly nephritis. On admission to antenatal control, 29/43 (65%) women were under treatment with prednisone, 21 with chloroquine (65.6%), and 11 (34.4%) with hydroxychloroquine. There was an increase in the average dose of prednisone during pregnancy of 20%. During the postnatal period, two patients had moderate lupus relapse.

Conclusions: Lupus nephritis and antiphospholipid antibodies were present in a significant proportion of the patients with obstetric complications. Even though a low percentage of patients presented lupus activity prior to pregnancy, maternal and fetal complications were frequent. Although the use of hydroxychloroquine during pregnancy is reported in the literature, the majority of women in this cohort received chloroquine, without a significant increase in lupus activity or the occurrence of obstetric complications.

80

STUDY OF THE CLINICAL PHENOTYPES SUGGESTIVE OF UNDIFFERENTIATED AUTOINFLAMMATORY DISEASES IN ADULT PATIENTS AND OF THE THERAPEUTIC MODALITIES USED IN THEM

Ricardo Bedón¹. ¹Hospital General Docente De Calderón, Quito, Ecuador, ²Universidad Central del Ecuador, Quito, Ecuador.

Objectives: The monogenic autoinflammatory diseases (AIFD) are characterized by recurrent or persistent episodes of fever, joint pain and other varied symptoms. They are caused by mutations in genes related to some inflammatory pathways. The presence of recurrent or continuous fever, as a guiding sign, in patients in whom an infectious and tumoral autoimmune cause could be ruled out and where the genetic study of the main ones AIFD is negative, confers an undifferentiated autoinflammatory genotype.

OBJECTIVES: To describe the clinical and biological characteristics of a cohort of patients with undifferentiated autoinflammatory diseases.

Methods: Analysis of recorded data (2014- 2016) of adult patients with undifferentiated AIFD from a unit of autoinflammatory diseases of the autoimmune diseases service of the Hospital Clínico de Barcelona. In order to identify and characterize the different clinical phenotypes, clinical and analytical data were obtained, at the time of diagnosis and during follow-up, as well as information on the treatments used and their efficacy.

Results: Of 107 patients suspected of having AIFD, 30 (28%) of them were diagnosed as Undifferentiated AIFD. Among them, the average age at the begining of the clinical picture was 27±14 years, with a predominance of women (63 %). Based on the prevailing symptoms, four phenotypes or complex systemic clinical syndromes were determined ( 47 % ), syndrome of periodic fever, aphthous stomatitis, pharyngitis and atypical adenitis (PFAPA atypical) ( 23% ), recurrent pericarditis ( 20% ) and Familiar Mediterranean Fever - like ( FMF- like ) ( 10% ).The drugs to which patients finally had an adequate response were colchicine ( 33% ), prednisone on demand (20% ) and Anakinra (anti- interleukin -1) ( 27% ). Patients with complex systemic pictures more frequently required (50%) Anakinra. In 20% of the patients a self-limiting course, was observed without requiring a specific treatment.

Conclusions: The undifferentiated AIFD can be grouped into characteristic phenotypes according to the predominant symptoms. Within the treatments used, Anakinra was the most common in those cases considered more complex.

85

ANALYSIS OF COPY NUMBER VARIATION AND THE POLYMORPHISM RS179008 (A>T) OF TLR7 GENE AND ITS ASSOCIATION WITH THE DEVELOPMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS IN TWO MEXICAN POPULATIONS

Guillermo Valencia Pacheco¹, Yumi E. Nakazawa Ueji¹, Julián Ramirez Bello², Rosa E. Barbosa Cobos³, Eduardo D. Jiménez Beccerra¹, Gerardo J. Perez Mendoza¹, and Nubia A. Rivero Cardenas¹. ¹Laboratorio de Hematología. Centro de Investigaciones Regionales Dr. Hideyo Noguchi, de la Universidad Autónoma, Yucatán, México, Mérida, ²Research Unit on Endocrine and Metabolic Diseases Hospital Juárez de México, Ciudad de Mexico, Mexico, ³Hospital Juárez de México, Ciudad de México, México.

Objectives: The mestizos of Yucatan are the only group whose Amerindian contribution is mainly Mayan, and they represent an ethnic group geographically distant from other Mexican Amerindian groups. Due to heterogeneity among mestizo subpopulations from geographically distant regions of Mexico, the study of genetic factors such as Copy Number Variation (CNV) or the Single Nucleotide Polymorphysm (SNP) in the TLR7 gene associated with the pathogenesis of SLE is important.

Objective: to analyze the CNV and SNP rs179008 (A> T) of the TLR7 gene and its association with with the development of SLE in mestizo patients from Yucatán and Mexico City.

Methods: The study was conduced including 151 female patients with SLE and 121 healthy female controls from Mexico City, and 100 female patients with SLE and 102 helathy females controls from Yucatan, who voluntarily agreed to participate in the study. Both CNVs and genotyping of SNP rs179008 (A>T) was determined by real-time PCR with TaqMan probes. The estimation of CNV was made by calculating 2-ΔΔCt. The allelic and genotypic frequencies were analyzed using the STATA 10 program. The association of CNV and SNP rs179008 (A>T) with the disease was analyzed by determining the Odds Ratio (OR) with a confidence interval of 95%, and the results were contrasted by the Chisquare test.

Results: We observed that 14% of the patients from Yucatán showed significantly more than 2 copies with respect to 4% of those from Mexico City. The association analysis shows that the Yucatecan women presents a higher risk of developing the disease (OR = 34.36, p = 0.0003) than those from Mexico City (OR = 10.85, p = 0.07). Regarding the SNP rs179008 (A> T), the wild allele A was found more frequent in patients and controls of Yucatán (74% and 76%) and Mexico City (51%) and 61%), while the T risk allele was less frequent. However, the T allele shows greater association with the disease in the patients from Mexico City (OR = 1.53, p = 0.01). The mutated A / T genotype presented a greater frequency and association with the disease in patients from Mexico City (OR = 9.75, p <0.0001).

Conclusions: Genetic studies of association and expression, based on the search of CNV and presence of SNPs of a gene, constitute a valuable tool to better understand the etiopathogenesis of the disease and identify genetic markers.

The results support the role of the TLR7 gene in the pathogenesis of SLE in Mexican mestizo populations and suggest that extra copies of the gene may be a risk factor for developing the disease. The presence of the mutated A / T genotype associated with the disease, mainly in patients from Mexico City, supports the genetic differences between and within Mexican mestizo populations.

89

CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: THE 2018 EULAR/ACR CRITERIA VS THE 1982/1997 ACR CRITERIA. A COMPARATIVE STUDY IN TWO MULTICENTER, MULTIETHNIC COHORTS

Manuel Ugarte-Gil^1,2, Guillermo Pons-Estel³, Russell Griffin⁴, Guillermina Harvey⁵, Daniel Wojdyla⁵, Luis M. Vilá⁶, Loreto Massardo⁷, Eloisa Bonfá⁸, Mario Cardiel⁹, Verónica Saurit¹⁰, Enrique Soriano¹¹, Bernardo Pons-Estel³, and Graciela S. Alarcón^12,13. ¹Universidad Científica Del Sur, Santiago De Surco, Perú, ²Hospital Guillermo Almenara Irigoyen. EsSalud, La Victoria, Perú, ³Grupo Oroño - Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina, ⁴Department of Epidemiology, University of Alabama at Birmingham, Birmingham, US, ⁵Facultad de Ciencias Económicas y Estadística, Universidad Nacional de Rosario, Rosario, Argentina, ⁶Division of Rheumatology. University of Puerto Rico, San Juan, US, ⁷Centro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia. Universidad San Sebastián, Santiago, Chile, ⁸Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de São Paulo, Sao Paulo, Brazil, ⁹Centro de Investigación Clínica de Morelia, Morelia, Mexico, ¹⁰Servicio de Reumatología, Hospital Privado Universitario de Córdoba, Cordoba, Argentina, ¹¹Sección de Reumatología, Servicio de Clínica Médica, Instituto Universitario, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, ¹²School of Medicine. The University of Alabama at Birmingham, Birmingham, US, ¹³Facultad de Medicina. Universidad Peruana Cayetano Heredia, Rímac, Lima, Perú.

Objectives: To determine the sensitivity of the 2018 EULAR/ACR criteria using two well-defined lupus cohorts.

Methods: Patients from two multiethnic and multicenter lupus cohorts, one from the US and the other from Latin-America were included. SLE patients were classified using the 1982/1997 ACR criteria in the US cohort and as diagnosed by expert physicians in lupus for the Latin-American cohort although more than 95% of these patients also achieved the 1982/1997 ACR criteria. For these analyses the 1982/1997 ACR criteria were used as the gold standard. Demographics and disease activity at baseline (measured with the SLAM for the US cohort, and with the SLEDAI for the Latin-American cohort) were compared in order to determine differences between those patients who achieved the EULAR/ACR criteria before, at the same time or after than 1982/1997 ACR criteria.

Results: Five-hundred and fifty-eight patients out of 640 from the US cohort and 956 out of 1047 from the Latin-American cohort achieved the EULAR/ACR criteria. The sensitivity of the EULAR/ACR criteria in the US cohort was 87.2% and in the Latin-American cohort was 91.3%; in the US cohort, 41 (7.3%) achieved the EULAR/ACR criteria earlier, 344 (61.6%) at the same time and 173 (31.0%) later than the ACR criteria; for the Latin-American cohort these numbers and percentages were 71 (7.4%), 556 (58.2%) and 329 (34.4%), respectively. Patients who achieved the EULAR/ACR criteria earlier were less likely to be Caucasian (12.2%) in the US cohort and 30.0% in the Latin-American cohort compared to those who achieved both criteria at the same time (21.2% and 52.0%) or the EULAR/ACR criteria later (37.6% and 47.0%); disease activity did not differ between the groups.

Conclusions: The sensitivity of the 2018 EULAR/ACR criteria vs. the 1982/1997 ACR criteria (gold standard) was high (87.2% for the USA and 91.3% for the Latin-American cohort). While the large majority of patients were classified at the same time (58.2% to 61.6%) with both criteria, about one third were classified later and a small proportion (about 7%) were classified earlier with the 2018 EULAR/ACR criteria. In this last group, the EULAR/ACR criteria seem to perform better in non-Caucasian populations. Further examination of the 2018 EULAR/ACR criteria is warranted.

103

ACCUMULATION OF ORGAN DAMAGE OVER TIME IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Susana Roverano¹, Romina Calvo¹, Alberto Ortiz¹, Sergio Paira¹, Lucas Costa², and Elena Carrera². ¹Hospital José María Cullen, Santa Fe, Argentina, ²Unidad Bioestadística Aplicada-UNL-FCM, Santa Fe, Argentina.

Objectives: Survival in Systemic Lupus Erythematosus (SLE) has improved in the last decades, hence, organ damage tends to accumulate over time.

We undertook this study in order to determine organ damage accumulation in patients who had been followed (at least some of them) for twenty - five years.

Methods: All SLE patients were followed at the Rheumatology Section of Cullen Hospital, (established in 1987). We took into consideration demographic data, time of follow up, treatment received, and SLICC-SDI calculated at 1st, 2nd, 5th, 10th, 15th, 20th and 25th year of follow up.

Results: 301 patients were evaluated; mean time of follow up: 5.52 years SD: 4.84-6.20) and mean age at diagnosis: 32.43 ± 12.6 years. Almost 50% of the patients had an SDI=0 at the 5th year of follow up. Organ damage increased over time: 1.58 at 1st year to 3.70 at 25th year. Renal, Musculoskeletal and Neuropsychiatric domains were the most involved in this follow up, while Gastrointestinal, Gonadal, Malignancies and Peripheral Vascular were less preponderant. Proteinuria, Arthritis and Seizures were the most common subtypes observed.

Conclusions: Gladman et al and Urowitz et al described early damage in Cardiovascular, Gastrointestinal and Skin domains. In our study Renal and Musculoskeletal System damage were the more commonly found. Treatments are more effective in SLE patients. Damage accrual may result from either treatment received or the disease itself.

106

PREVALENCE OF HOSPITAL DISCHARGES DUE TO SYSTEMIC CONNECTIVE TISSUE DISORDERS IN ECUADOR AND THEIR GEOGRAPHICAL DISTRIBUTION

Michelle Fuseau Herrera¹, David Garrido Salazar², Líder Escudero Abad², and Diego Noboa Torres^2,3. ¹Universidad de la República, Montevideo, Uruguay, ²Hospital de Especialidades de las Fuerzas Armadas N°1, Quito, Ecuador, ³Universidad Central del Ecuador, Quito, Ecuador.

Objectives: To determine the prevalence of hospital discharges due to systemic connective tissue disorders in Ecuador, as well as the specific characteristics of patients and their geographical distribution.

Methods: This is a transversal descriptive study conducted in Quito, Ecuador. Based on the analysis of discharge hospitalization diagnosis, coded according to the International Classification of Diseases (ICD) as Systemic Connective Tissue Disorders (SCTD), which includes polyarteritis nodosa and related conditions (M30), other necrotizing vasculopathies (M31), systemic lupus erythematosus (M32), dermatopolymyositis (M33), systemic sclerosis (M34), other systemic involvement of connective tissue (M35), systemic disorders of connective tissue in diseases classified elsewhere (M36); from a secondary source published by the Instituto Nacional de Estadisticas y Censos (INEC, National Institute of Statistics and Census) of Ecuador entitled “Registro Estadístico de Camas y Egresos Hospitalarios, 2017”, which presents information of all the Ecuadorian public and private health establishments with hospitalization, collected during 2017. Data were analyzed by sex, age groups, and province of residence.

Prevalence was calculated by 100000 inhabitants using the tabulated data through Excel, using the latest version of SPSS software package.

Results: Of 1482 patients found, 1173 (79.15%) were female, being the prevalent group in all the diagnostics (female-to-male ratio 4:1) excepting in Polyarteritis nodosa and related conditions, where male children from 1 to 4 years were the prevalent group.

A higher prevalence during the reproductive years was observed; peaking between 23 and 34 years with 344 patients (23.48%), followed by individuals between 35 and 44 years (17.54%). The most frequent diagnosis was systemic lupus erythematosus (SLE) with 1125 cases (76%), from them, 973 (86.49%) were female (female-to-male ratio 6:1).

We found higher prevalence rates of SCTD by 100000 inhabitants in Pichincha 19.67 and Imbabura 11.36, contrasting to the rest of the country which prevalence rates varies from 0.80 in Napo to 9.30 in Carchi. The difference between the observed means was -9.99 (95% CI -14.2351 to -5.7449; p-value < 0.0001), reflecting a significantly higher prevalence of SCTD in Pichincha and Imbabura.

Conclusions: SCTD are more frequent in women, during the reproductive years. The only predominance of male observed was in children with ICD code M30, surely corresponding to the subcategory Mucocutaneous lymph node syndrome (Kawasaki).

Despite not having the diagnoses distribution by province, SLE was the predominant diagnosis.

The significantly higher prevalence rates of SCTD detected in Pichincha and Imbabura requires the strengthening of medical personnel and hospitals for identifying and managing these pathologies, especially in these provinces.

Demographic data and possible predisposing factors have to be investigated and correlated in further studies.

107

JOINT INVOLVEMENT IN PRIMARY SJÖGREN’S SYNDROME PATIENTS

Oscar Andrés Caicedo Correa¹, Silvia Papasidero¹, Silvana Karina Pérez¹, Juan Bande¹, Alejandra Medina¹, Julia Sosa¹, José Angel Caracciolo¹, Rafael Chaparro Del Moral¹, Anastasia Secco², Diego Puente Trigo², Marina Gauna², Antonio Catalan Pellet², Oscar Rillo³, Alejandro Nitsche⁴, Catherine Crow⁴, Andrea Gómez⁵, Federico Zazzetti⁵, Sofía Vélez⁵, Juan Carlos Barreira⁵, Nadia Raquel Benzaquén⁶, Laura Encinas⁶, Francisco Caeiro⁶, Eduardo Albiero⁷, Natalia Tamborenea⁸, Gabriela Salvatierra⁹, and Laura Raiti¹⁰. ¹Hospital General de Agudos Dr. "Enrique Tornu", Buenos Aires, Argentina, ²Hospital General de Agudos "Bernardino Rivadavia", C.A.B.A., Argentina, ³Hospital General de Agudos Dr. “ Ignacio Pirovano”, C.A.B.A., Argentina, ⁴Hospital Alemán, C.A.B.A., Argentina, ⁵Hospital Británico, C.A.B.A., Argentina, ⁶Hospital Privado De Córdoba, Córdoba, Argentina, ⁷Hospital Córdoba, Córdoba, Argentina, ⁸Organización Médica de Investigación, C.A.B.A., Argentina, ⁹Instituto Provincial de Rehabilitación Integral, Santiago del Estero, Argentina, ¹⁰Clínica Bessone, San Miguel, Argentina.

Objectives: Primary Sjögren's Syndrome (pSS) is a chronic autoimmune disease characterized by progressive mononuclear infiltration of the exocrine glands, presenting oral and ocular dryness as main clinical manifestations. A variety of organs can be affected, being the joints frequently involved. The aim of this study was to describe the frequency of arthritis and arthralgia in patients with pSS; to evaluate the joint involvement, and to analyze its association with other clinical and serological manifestations.

Methods: Multicentre, observational and analytical study. Patients with pSS (ACR/EULAR criteria) included in the pSS study group database from the Argentine Society of Rheumatology. Demographic data, clinical manifestations, laboratory findings and complementary studies were recorded. In order to compare patients with joint involvement (arthralgia and/or arthritis) vs those without it, individuals who subsequently developed rheumatoid arthritis (RA) or other connective tissue disorder were excluded. A subgroup of patients with joint involvement was analyzed to characterize the joint involvement.

Results: Two hundred and fifty-nine patients were analyzed: 91% women, mean age 58 years (SD 3.5). Seventy percent presented arthralgia or arthritis. Joint involvement was analyzed in 86 patients. A greater frequency of metacarpophalangeal and carpus involvement was observed in the arthritis group (56% vs 50%). In the group with arthralgia, the most affected joints were knees (40%) and proximal interphalangeal (40%). Polyarticular and intermittent involvement was the predominant pattern. Erosive lesions were reported in 3 patients, only 1 met criteria for classification for RA. When compared with the group without joint involvement, some statistically significant differences were observed: greater proportion of parotid swelling (40% vs 20%, p = 0.004) and positive RF (66% vs 44%, p = 0.002). In the logistic regression analysis, the variables associated with joint manifestations were: RF + (OR 2.5, 95% IC: 1.3-4.7) and parotid swelling (OR 2.4, 95% IC: 1.1-5.0).

Conclusions: We found that 70% of patients with pSS had joint involvement and this was associated with the presence of parotid swelling and positive RF. In addition, we highlight the finding of erosive lesions (as they are rare in pSS) in 3 patients.

109

RELATIONSHIP BETWEEN BODY MASS INDEX AND INTERSTITIAL LUNG DISEASE IN SCLERODERMA PATIENTS

Daniel Rivas-Vargas¹, Francisco Bustamante¹, Soham Al Snih², and Martin Alberto Rodríguez¹. ¹Hospital Universitario De Caracas, Caracas, Venezuela, ²División of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Estados Unidos.

Objectives: To determine the association between body mass index (BMI) and interstitial lung disease (ILD) in patients with scleroderma.

Methods: A cross-sectional, correlational, non-probabilistic sample, of consecutive patients with scleroderma seen in the Rheumatology Division at the Hospital Universitario de Caracas during the period of April to September 2018. Patients underwent clinical and laboratory assessments, anthropometric measurements, pulmonary function tests, high-resolution computed axial tomography scan of the chest and full-body densitometry.

Results: Of 48 patients, 95.8% were female, 64.6% had limited cutaneous scleroderma. Underweight [Body Mass Index (BMI) < 18.5 Kg/m2] was a risk factor associated with ILD (OR 4.60, 95% CI 1.12-18.86). BMI was related in a fashion directly proportional to forced vital capacity (FVC) (CC 0.35, p=0.0152). Predictors of ILD included diffuse scleroderma (OR 6.91, 95% CI 1.78-26.85), modified Rodnan Skin Score (mRSS) (OR 1.25, 95% CI 1.04-1.30) and a speckled pattern of antinuclear antibody (ANA) (OR 5.62, 95% CI 1.33-23.62). Multivariate analysis showed that mRSS (OR 1.34, 95% CI 1.04-1.72) and the presence of a speckled ANA (OR 25.99, 95% CI 1.02-662.02) were independent predictors of ILD. The percentage of BMI lost in a period of time of 2008-2018 was 14.3% (p=0.0021), which was higher than in patients with rheumatoid arthritis (p=0.0000), systemic lupus erythematosus (p=0.0025) and healthy subjects(p=0.0331)

Conclusions: Underweight was a risk factor associated with ILD in scleroderma patients. The mRSS could be used as a clinical predictor tool for ILD in scleroderma.

111

OPHTHALMOLOGIC MANIFESTATIONS IN SYSTEMIC SCLEROSIS AND THEIR ASSOCIATION WITH THE EXTENT AND SEVERITY OF CUTANEOUS FIBROSIS. LIMA - PERÚ

Janeth Villegas Guzmán¹, and Bety Yañez Alvarez¹. ¹Hospital Nacional Dos de Mayo, Lima, Perú.

Objectives: To determine the frecuency and type of ophthalmologic manifestations in systemic sclerosis (SSc) and establich their association with the extent and severity of cutaneous fibrosis.

Methods: Descriptive – cross-sectional study of 34 patients (January-December 2017). It included patients with Limited cutaneous systemic sclerosis (lcSSc) and Diffuse cutaneous systemic sclerosis (dcSSc). The severity of cutaneous fibrosis was measured using the modified Rodnan skin score (mRSS). Eye examination included: palpebral skin, ocular surface by Schirmer test, time of rupture of teardrop (BUT), the severity of the symptom of dry eye was evaluated through OSDI (Ocular disease surface index) and SANDE (symptom questionnaires assessment in dry eye). The posterior segment eye and retinography fund was evaluated. Applied logistic regression (OR) and Fisher test with p< 0.05 were applied.

Results: 21 patients (61.7%) had dcSSc and 13 patients (38.2%) lcSSc. Women 31 (91.2%). Average time of disease 67.4 months. The mRSS was mild in 14 (41.2%) and moderate - severe in 20 (58.8%). Findings: palpebral fibrosis 30 (88.2%), keratoconjuntivitis sicca (KCS) 26 (76.5%), blepharophimosis 20 (58.8%) and enophthalmos 7 (20.6%), alteration of the retinal pigment epithelium 3 (8.8%). Associated with the extension, dsSSc had significant statistical association with blepharophimosis (p=0.00). KCS mild in both groups with Schirmer test and BUT positive, but no significant association. In terms of the severity of cutaneous fibrosis with mRSS, we found a significant statistical association between enophthalmos (p=0.01) and blepharophimosis (p=0.00) with a moderate- severe score.

Conclusions: The most common alterations of the anterior segment were: fibrosis of the skin of the eyelids and its complications as enophthalmos and blepharophimosis together with KCS. dsSSc patients in moderate to severe extent have high risk of having complications from the palpebral fibrosis: enophthalmos and blepharophimosis. KCS appears to be independent of the severity or the extension.

Eye evaluation and effective treatment of the SSc is important for a better visual prognosis.

112

SUBCUTANEOS PANNICULITIS – LIKE T CELL LYMPHOMA MIMICKING LUPUS ERYTHEMATOSUS PANNICULITIS

Claudia Maldonado¹, Nelson Zambrano¹, Mario Moreno¹, Enrique Loayza¹, and Juan Carlos Garcés¹. ¹Hospital Luis Vernaza, Guayaquil, Ecuador.

Objectives: Lupus erythematosus panniculitis (LEP) is a type of cutaneous lupus erythematosus that occurs up to 1-3% of patients. Most frequent localizations are upper extremities, trunk and face. Subcutaneous panniculitis T-cell lymphoma (SPTCL) is a rare type of lymphoma represented in less than 1% of skin cell lymphomas, it is common in women and can occur at any age. There are some cases of SPTCL and LEP that demonstrate clinical and histopathologic overlap raising the possibility that they represent opposite ends of a disease spectrum.

Methods: CASE REPORT: Female, 39 years old, with history of choriocarcinoma 14 years before treated with EMACO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), who presented skin plaques of 12 years in duration, infiltrated with painful nodules, localized in the arms and trunk, accompanied by recent prolonged fever, malaise, asthenia and weight loss. Her laboratory results were negative for ANA, DNA, ENA and low complement. A deep skin biopsy of her left arm revealed a pattern similar to a lobular panniculitis with atypical lymphocytes rimming the adipocytes. CD20, CD3, CD4 markers were negative, but immunohistochemistry for CD8, Ki 67 hotspots were positive which confirmed the diagnosis of SPTCL. The patient was treated with CHOP chemotherapy. Afterward, ultrasonography and histopathologic control only showed a residual panniculitis with dystrophic calcification.

Results: DISCUSSION: SPTCL is a type of cutaneous lymphoma characterized by the subcutaneous infiltration of cytotoxic T cells which have a α/β T-cell phenotype. It affects predominantly young adults. Histologically, the subcutaneous infiltrates simulate a lobular panniculitis with the presence of fat rimming by pleomorphic T cells which is a useful diagnostic feature. Due to both clinical and histological similarity, some authors believe that this is an advanced stage of the same disease in which LEP is transformed into SPTCL. The main difference in the histological diagnosis is that by inmunohistochemistry staining SPTCL is CD8 positive, but LEP is positive for CD123.

Conclusions: This is an unusual case of subcutaneos panniculitis – like t cell lymphoma mimicking lupus erythematosus panniculitis. Given that SPTCL and LEP can show significant overlap, it is necessary to perform complementary studies to make an adequate differentiation.

114

METABOLIC SYNDROME IN LUPUS AND RELATIONSHIP WITH THE NEUTROPHIL TO LYMPHOCYTE RATIO

Vanessa Castro Coello¹, Demelza Yucra Bobarin¹, Gabriela Garate Correa¹, Adriana Hamaui¹, and Diana Dubinsky¹. ¹Sanatorio Güemes, CABA, Argentina.

Objectives: In SLE there is five times higher risk of cardiovascular events (CV) compared to the general population. In Argentina, the prevalence of metabolic syndrome (MetS) is 28%. The SLICC cohort of early SLE found 36.5%. The neutrophil to lymphocyte ratio (NLR) is a tool in the assessment of CV risk and systemic endothelial dysfunction. The NLR values reported in healthy is 1.65 (±SD 1.47). Studies in SLE show that NLR is a marker of activity and nephritis. We aimed to determine the association of MetS with and without renal involvement, the relationship between NLR with MetS and disease activity.

Methods: Descriptive, cross-sectional study. Patients with SLE (SLICC 2012) of <5 years of disease duration and > 18 years followed at the Güemes Hospital were included, between 06/2013 to 07/2018. Acute cardiovascular events, infections, pregnancy, diabetes and chronic kidney disease were excluded. Traditional risk factors associated with the disease were determined: antiphospholipid (aPL), GC, SLEDAI. MetS was defined according to NCEP ATP III criteria. Laboratory: neutrophil and lymphocyte count, glucose, CT, TG, HDL, LDL, urea, creatinine, proteinuria/24hs, Anti DNA, C3, C4, aPL: LA, B2GPI IgG and Anti aCL antibody. Statistical Analysis: it is presented as means and percentages. T Test or Mann Whitney to compare independent variables according to their distribution. For inferential statistics: Student's t-test and Chi-square test (χ²) for qualitative variables. Statistically significant: p <0.05. Epi Info 7.2.0.1 was used.

Results: A total of 42 patients were reviewed, 12 were excluded (incomplete data). Of 30 patients: 23 women (77%), mean age 39.3 (± SD 14.3), disease duration: 35 months (± SD 18.9), tobacco exposure: 11 (37%). Nephritis in 17 patients (51%). MetS: 13 (43.3%). The correlation of proteinuria of the group with Mets: 1.2 g/d (± SD 3.19) vs the group without MetS 0.35 g/d (± SD 0.54) was statistically significant p = 0.03; likewise, the CRP was higher in the group with MetS vs whitout MetS (p = 0.02). The NLR in MetS was 3.42 (± SD 1.32), in nephritis 3.35 (± SD 1.62) and in patients with SLEDAI ≥ 4 was 4.43 (± SD 1.42).

Conclusions: In our series, a greater frequency of MetS was found than in the literature. No relationship was found between MetS and renal involvement; however, patients with MetS had higher proteinuria and elevated CRP. No relationship was found between the NLR with MetS and nephritis. The NLR was higher in patients with SLEDAI ≥ 4. The high prevalence of MetS, proteinuria, elevated CRP and NLR in our population suggest persistent inflammatory activity and probable CV morbidity, so it is important to detect it from the onset of the disease.

119

RHEUMATOID FACTOR IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Diana Gabriela Gárate Correa¹, Demelza Yucra¹, Ruth Balcazar¹, Adriana Hamaui¹, and Diana Dubinsky¹. ¹Sanatorio Guemes, Argentina

Objectives: Rheumatoid factor (RF) in SLE is found in around 25% of patients. Authors associate its presence with cutaneous involvement, Sicca, anti Ro (+) and a protective role in glomerulonephritis (GMN), suggested by the finding of less frequent and less severe nephritis in lupus patients with RF (+) as in patients with RA.

The proposed protective mechanisms of RF include preventing the complement from joining immune-complexes (IC) and avoiding the IC deposition in the glomerulus (1,2,3).

We aimed to determine the clinical and immunological profile of SLE patients with and without RF and to determine the association between RF and GMN.

Methods: Descriptive medical records review study of SLE (SLICC 2012) patients selected from the Rheumatology department of Güemes Hospital, from January 2015-August 2018.

We collected data on demographics, cutaneous-articular, renal, hematological and CNS involvement. Immunoserology: RF IgM by immunoturbidimetric (+) > 30 UI/ml, anti Ro, anti La, anti Sm, anti RNP (ELISA), ANA (Hep 2), Anti DNA (Crithidia lucilliae), C3, C4, aPL at least one of the following: Lupus anticoagulant, anti β2GP1 IgG/IgM, anti aCL IgG/IgM.

Results: We reviewed 147 clinical histories, 107 with RF ordered. Female 93/107 (86.9%), mean age 41.6 years (SD±13.8). Disease duration 98 months (SD±80.6). Tobacco exposure 10/107 (9.35%). RF (+) 22/107 (20.5%), RF median titer 228.8 IU/ml (31-2825 IU/ml).

RF level in patients with GMN was 142 IU/ml (39-191), without GMN 258 IU/ml (31-2825) p= 0.46.

RF level in patients with anti Ro (+) was 248 IU/ml (31-2825), Ro (-) 52.5 IU/ml (31-74) p= 0.37.

RF (-) subgroup showed statistically significant association with female sex, discoid lesions and aPL presence. RF (+) was associated with Ab Ro, La and patients with RA.

No significant association with rash, photosensivity, oral ulcer, joint pain, arthritis, serositis, neurologic and hematological involvement was found.

In those with GMN, we found a significant association with Ab Ro (+) in the absence of RF.

Conclusions: Similar RF frequency was found in our lupus patients as in the published literature. There was no association with GMN, but the mean RF titer was higher in patients without it.

The detection of Ab clusters associated with RF may be useful in suggesting the absence of renal involvement.

120

SYSTEMIC LUPUS ERYTHEMATOSUS PANCREATITIS: CASE REPORT

Fiorella Lizeth Vilca Salguero¹, Arquimedes Hidalgo García¹, Janeth Villegas Guzmán¹, Angela Chuquihuara Rodriguez¹, César Cefferino Hidalgo¹, Delinda De la Cruz Albújar¹, Joel Peláez Troncos¹, María Pacheco Alfaro¹, Diana Yactayo Silva¹, and Mayra Paredes Ballena¹. ¹Hospital Nacional Dos De Mayo, Lima, Perú.

Objectives: To describe a case of severe acute pancreatitis as a manifestation of systemic lupus erythematosus (SLE).

Methods: Clinical case report and literature review.

Results: A 24-year-old woman with SLE, grade IV nephritis and optic neuromyelitis under treatment with cyclophosphamide, presented to the emergency department with a one-day history of epigastralgia, with and intensity 9/10, not relieved by analgesics and associated with vomiting and hyporexia. Denied: alcohol use, use of azathioprine or gallbladder lithiasis.

On physical exam she presented easy hair detachment, oral ulcers; her abdomen was distended, depressed and painful to palpation in epigastrium and right hypochondrium. Arthritis of hands. Leukocytes 1170, lymphocytes 386, platelets 123000, Hemoglobin 9, amylase 801 (<110), lipase 14424 (<300), CRP 177mg / L, C3, C4 decreased. Proteinuria: 2 gr/24hrs.

Abdominal ultrasound: gallbladder without stones, signs of pancreatic inflammation, free fluid in cavity. TEM abdomen: Signs of pancreatitis. Colangioresonance: Signs of acute pancreatitis, absence of choledocholithiasis. Severe acute pancreatitis was diagnosed in the ICU. She received five pulses of methylprednisolone, with favorable clinical and humoral evolution, reason why it was concluded that the cause was autoimmune.

Conclusions: Pancreatitis as a gastrointestinal manifestation of SLE has a frequency of 0.7 - 4%, in 22% it is the initial clinical manifestation. Despite its low frequency, in the presence of acute abdominal pain, it must be considered in the differential diagnosis; even more if there is lupus activity since it is associated with a high mortality. This manifestation responds well to high doses of corticosteroids, as evidenced in our case, where timely diagnosis and treatment led to the remission of pancreatitis.

121

LUNG CANCER IN SYSTEMIC LUPUS ERYTHEMATOSUS: A CASE REPORT

Arquímedes Hidalgo García¹, Diana Yactayo Silva¹, María Pacheco Alfaro¹, Janeth Villegas Guzmán¹, César Cefferino Hidalgo¹, Angela Chuquihuara Chuquihuara Rodríguez¹, Delinda De La Cruz Albújar¹, Joel Peláez Troncos¹, Mayra Paredes Ballena¹, and Fiorella Vilca Salguero¹. ¹Hospital Nacional Dos De Mayo, Lima, Perú.

Objectives: To describe the presentation of lung cancer in a patient with systemic lupus erythematosus (SLE).

Methods: Clinical case report and literature review.

Results: A 54-year-old woman with a diagnosis of SLE for 8 years, without a history of smoking. Request a consultation because of the presence of pleuritic pain in the posterior region of the right hemithorax and dyspnea of 2-months in duration. Denied: fever, night sweats, weight loss. On physical examination in right hemithorax: decreased amplexation, decreased vocal vibrations in 1/3 medium and abolished in the lower 1/3, egophony in the lower 2/3, absence of vesicular murmur in the lower 2/3 with dullness on percussion Study of pleural fluid: leukocytes: 3120 cells / mm3, red blood cells: 250 cells / mm3, polymorphonuclear cells: 0%, mononuclear: 100%, BK and GeneXpert: negative. Tumor markers: negative. Chest x-ray film: pleural effusion and heterogeneous radio-opacity in the right hemithorax. Chest tomography with contrast: lung mass in the middle of the right lung measuring: 84x55x27 mm with mediastinal adenopathies, effusion and pleural thickening. Cytological study, cell block and immunohistochemistry compatible with pulmonary adenocarcinoma.

Conclusions: SLE is associated with an increased risk of several types of cancer, including the lung with a 1,62 times increased risk in SLE. A Colombian study found a frequency of 4.4% of diverse neoplasms in SLE, but not of lung.

Lung cancer in SLE occurs on average at 60 years of age, late in the course of SLE, is strongly associated with a history of smoking; the most common histological type is adenocarcinoma and in 85% of the cases they are in advanced stages III / IV, being associated with a poor prognosis.

123

RENAL TRANSPLANTATION IN SYSTEMIC LUPUS ERYTHEMATOSUS: EXPERIENCE IN A SINGLE CENTER IN GUATEMALA

Valeria Rodríguez Cárcamo¹, Nilmo Chávez¹, Silvia Rivera¹, Estuardo Anzueto¹, and Vinicio Montúfar². ¹Department of Rheumatology, Guatemalan Social Security Institute, Guatemala, ²Department of Nephrology, Guatemalan Social Security Institute, Guatemala

Objectives: Renal involvement in systemic lupus erythematosus (SLE) is one of the main causes of morbidity and mortality. The risk for progression to end-stage kidney disease (ESRD) secondary to lupus nephritis (LN) in native kidneys has been estimated to be up to 30%. The objective of this study was to analyze the long-term outcome of patients with NL who underwent renal transplantation from a single center in Guatemala.

Methods: This is a medical records review study that included all adult patients diagnosed as having SLE in whom ESRD was primarily caused by lupus nephritis, who required renal transplantation from January 2005 to December 2017 in the Guatemalan Social Security Institute. Medical records of hospitalizations and follow-up of LN patients with a kidney transplant were reviewedf. All patients met the criteria for classification of the American College of Rheumatology for SLE. The diagnosis of LN was based on the findings of the renal biopsy, by the International Society of Nephrology/Society of Renal Pathology (ISN/RPS) 2003 Classification system. To perform the analysis, demographic and clinical characteristics, histological and immunologic features, and treatments used in the cohort of SLE transplanted patients were evaluated. Patient and graft survival rates were calculated with Kaplan-Meier survival curves.

Results: A total of 13 renal transplants were performed in 13 patients diagnosed with LN, during the 12-year interval. Most patients were women (n = 9, 69%), with a mean age of 37.4 ± 10 years at the time of transplantation. Twelve patients (92.3%) underwent hemodialysis before renal transplantation and 54% had such treatment less than 3 years. The most frequent lupus nephropathy was type IV (62%). Among the comorbidities of patients who received a kidney graft, 54% had arterial hypertension. Four transplants were performed from deceased donors and nine from living-related donors. The patient survival rate was 100%, and graft survival was 84.6% at 1 year. Graft failure occurred in a total of 2 transplantations and the causes were chronic allograft nephropathy and acute rejection. Only 1 patient presented a recurrence of lupus nephritis, which was placed on rescue therapy with Rituximab, with a renal graft currently functional.

Conclusions: Renal transplantation is a method which can provide a long-term survival for patients with SLE and end-stage renal disease at the Guatemalan Social Security Institute, as reported in other studies in Latin America.

127

LET’S TALK ABOUT LUPUS LIVE VIDEO CHATS WITH AN EXPERT: AN INTERACTIVE FACEBOOK RESOURCE FOR PATIENT EDUCATION ABOUT LUPUS

Yurilis Fuentes-Silva¹, Claudia Elera-Fitzcarrald², Cristina Reátegui-Sokolova², Soledad Ibañez³, Carlota Acosta⁴, María Linares-Contreras⁵, Bernardo Pons-Estel⁶, and Cristina Drenkard⁷. ¹Universidad de Oriente, Ciudad Bolívar, Venezuela, ²Hospital Guillermo Almenara Irigoyen, Lima, Perú, ³Sanatorio Güemes, Buenos Aires, Argentina, ⁴Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Venezuela, ⁵Sociedad Venezolana de Reumatología, Caracas, Venezuela, ⁶Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Sanatorio Parque, Rosario, Argentina, ⁷Emory School of Medicine, Atlanta, USA

Objectives: The Latin-American population living with lupus is eager to learn about the disease and how to deal with a variety of illness-related challenges. We describe the methodology and impact of a Facebook (FB) resource that provides patient-centered education in Spanish through live interaction between members of the audience and Latin-American healthcare professionals with expertise in lupus.

Methods: FB/Hablemos de Lupus (Let’s Talk about Lupus) is part of a comprehensive online program in Spanish to educate Latin-Americans about lupus. While FB/Hablemos de Lupus delivers a continuous stream of educational resources, a team of rheumatologists addresses members’ questions and evaluates the audience education needs. In July 2017, we launched monthly live video chats (LVC) led by healthcare professionals with expertise in lupus. LVC include a short overview of the topic by the expert, followed by the audience-expert chat. Experts received personalized training on the use of the FB tool, and guidance to leverage the live questions as opportunities to educate without providing diagnosis or treatment recommendations. A LVC team assisted the experts by collecting and tracking the live audience questions in a shared document. We measured FB LVC metrics (number of shares, likes, comments; people reached; times content was displayed; total views; total views by age, sex and location).

Results: By November 2018, FB/Hablemos de Lupus has broadcasted 12 LVC. Topics were selected from the most common themes that emerged organically from the FB audience. Most LVC were led by rheumatologists from the Latin-American Group for the Study of Lupus (GLADEL) and lasted between 40 to 60 minutes. The overall live audience included 3,319 people across 12 LVC. Among them, 90% were female (63% aged 25-54; 27% aged 35-44). All Latin-American countries were represented, with Mexico, Argentina, Colombia, Chile and Perú as the top 5. The largest non-Latin American audiences were from Spain and the United States. Means of LVC impressions (times the content was displayed), people reached (people who watched 12 LVC) and LVC views (times the LVC was viewed) were 112717, 80248 and 17867, respectively. Mean shares, likes and comments were 447, 1709 and 587, respectively. Experts valued the experience and were willing to participate in further sessions.

Conclusions: FB/Hablemos de Lupus LVC engaged large Spanish-speaking audiences across all Latin-American countries and around the world, reaching out lupus patients and caregivers from both populated and remote places. The live interaction with Latin-American rheumatologists and other qualified healthcare professionals appears to be an appealing and cost-effective resource to educate and empower people living with lupus. Latin-American experts were highly satisfied with the experience and valued the potential benefits of providing education via Facebook live video chats.

128

CLINICAL FEATURES OF A GROUP OF PATIENTS WITH GIANT CELL ARTERITIS OF THE GHSV HOSPITAL AND THE NHC OF STRASBOURG

Felipe Mosquera Moyano^1,5, Murielle Rondeau-Lutz², Jean-Christophe Weber², Gabriela Zambrano Sánchez⁴, and Ramiro Cevallos³. ¹Pontificia Universidad Católica Del Ecuador, Quito, Ecuador, ²Nouvel Hôpital Civil, Strasbourg, France, ³Clinique Ste. Anne (GHSV), Strasbourg, France, ⁴Universidad Tecnológica Equinoccial, Quito, Ecuador, ⁵Hospital de Especialidades Carlos Andrade Marin, Quito, Ecuador

Objectives: Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica are the most common inflammatory conditions affecting the elderly population all over the planet. Both diseases share similar clinical, demographic and pathological features and often overlap in the clinical setting. Our study aims to determine the characteristics of the patients with GCA or PMR admitted in the Clinique Ste. Anne and the NHC of Strasbourg during a ten-year period.

Methods: We performed a medical record review descriptive analysis of the medical records in both the NHC and the Clinique Ste Anne of Strasbourg during a ten-year period going from 2004 to 2014 in which we identified 145 medical records in which the diagnosis of GCA or PMR had been registered. We constructed a database collecting the information concerning the clinical, biological, and pathological features of every patient as well as the treatment options used. The database was tabulated in order to perform standard statistical measures.

Results: Sixty-eight patients met all the inclusion criteria for our study, 75% were female (n=51). The chief complaint cited as the reason for hospitalization was a form of malaise (defined in Medical French as “alteration de l’etat general”) in 49% of the patients. The most common clinical history was the presence of cardiovascular disease found in 62% of the patients. Physical examination showed that the most prevalent disturbances were found in the musculoskeletal system corresponding to 36% (n=21) of all the cases. PMR was diagnosed in 60% (n=41) patients, while classic GCA was diagnosed in 25% of the patients and a form with mixed features was identified in two cases. Fifty-eight of all patients underwent a temporal artery biopsy in which a histolopathological diagnosis of GCA was found in 40% (n= 21) of all biopsies regardless of their clinical diagnosis.

Conclusions: This study highlights the importance of GCA and PMR in populations of European descent. It is to be remarked the high prevalence of cardiovascular diseases present in our group of patients which further highlights the importance of the disease as a significant cardiovascular risk factor in the elderly.

133

AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN SYSTEMIC SCLEROSIS

Alejandro Nitsche¹, Vera Milovic¹, Alejandro Requejo¹, and Juan Real¹. ¹Hospital Alemán, Ciudad Autónoma De Buenos Aires, Argentina.

Objectives: There are no specific treatments for Systemic Sclerosis (SSc). Some immunosuppressive or biological therapies offer benefit in skin tenderness and organ involvement. Meta-analysis, randomized trials and systematic reviews have demonstrated effectiveness of autologous hematopoietic stem cell transplantation (AHSCT) in SSc. Nonsmoker patients with early, diffuse and rapidly progressive SSc with mild pulmonary or renal involvement had better long-term event-free survival and overall survival, significant improvement in modified Rodnan score (mRS), pulmonary functional stability and better quality of life than those treated with cyclophosphamide (CY). AHSCT related mortality is nearly 10% versus patients treated with CY during the 1st year.

Methods: Case: 62 years old male patient with diffuse SSc with a disease duration of 14 years and a previous and stable mRS of 10 points. In 2017: severe and rapid progression of skin involvement with a mRS of 38 points, massive face telangiectasia, worsening of digestive features and 8 kg of weight loss. Secondary disease was ruled out. We discussed two treatment options: CY or RTX versus AHSCT but we favored the last one although, our patient had a SSc of more than 5 years in duration.

Results: AHSCT procedure: 1- autologous stem cell (ASC) mobilization with 5 days SQ filgastrim, 2-ASC recollection by venous leucapheresis with CD34+ selection. 3-A total of 11x10/6/kg ASC were recovered, 4-the patient was then admitted to the Hospital for non-immunoablative regimen: thymoglobulin: 6.5 mg/kg and CF 200 mg/kg; 5 days. Prophylaxis with fluconazole, ciprofloxacin and acyclovir were initiated, 5-Two days later, ASC were administrated through a central venous catheter, 6-Filgrastim 5ug/kg was added and at the 3rd day the patient had severe pancytopenia. Seven days after ASC administration, red and white cells begun to recover as well as platelets. At the 12th day the patient was discharged with acyclovir and trimethoprim sulfamethoxazole. After 11 months, our patient recovered appetite and gained weight, mRS decreased to 9 points, digestive manifestations disappear and improved the quality of life.

Conclusions: To our knowledge, this is the first SSc patient treated with AHSCT in Argentina. To minimize the AHSCT related mortality risk we need to identify patients with the highest possibility to improve (diffuse and rapid skin involvement - mRs >15-20-, <5 yrs disease, without or mild systemic damage) and lowest risk of complications. An expert team with a rheumatologist, cardiologist, pulmonologist and transplantation physician in a specialized center is required. Patients with early, diffuse rapidly progressive SSc have increased disease related-mortality (30%-50% at 5 years). AHSCT is a valid therapeutic option that can reverse the course of disease by “immune system resetting.”

136

CLINICAL MANIFESTATIONS OF SYSTEMIC SCLEROSIS

Nadia Riscanevo¹, Maria Haye¹, Janet Flores¹, Diego Baenas¹, Verónica Saurit¹, Cecilia Alvarez¹, Alejandro Alvarellos¹, Francisco Caeiro¹, and Soledad Fiorentino¹. ¹Hospital Privado, Córdoba, Argentina

Objectives: Systemic sclerosis (SSc) is a connective tissue disease characterized by activation of the immune system involving T and B lymphocytes, microvascular changes such as Raynaud's phenomenon, abnormal capillary architecture, digital ulcers, extended fibrosis of skin and internal organs. We aimed to establish frequency, clinical pattern and pharmacological interventions in patients with SSc.

Methods: Patients who fulfilled the ACR / EULAR 2013 criteria for SSc were selected from the Rheumatology Department at Hospital Privado Universitario Córdoba/Argentina.

A descriptive and cross-sectional study was conducted including patients diagnosed with SSc between February 2012 and December 2017.

Patients were classified into the following groups: limited cutaneous scleroderma (lcSSc), diffuse cutaneous scleroderma (dcSSc) and systemic sclerosis sine scleroderma (ssSSc).

The clinical manifestations evaluated were: Raynaud's phenomenon (RP), gastroesophageal reflux disease (GERD), telangiectasia and digital ulcers (DUs).

Data on capillaroscopy were classified as scleroderma pattern absent or compatible.

Doppler echocardiography was performed for screening pulmonary arterial hypertension (PAH).

The presence of interstitial lung disease (ILD) was assessed using chest CT.

Results: 61 patients were included; 93% were female, the median age at time of diagnosis was 49 ± 16 years.

46 patients (75%) presented lcSSc, 10 patients (16%) presented dcSSc, 5 patients (8%) presented (ssSSc).

The clinical manifestations: RP 59 (97%), GERD 54 (88%), telangiectasia 40 (66%), DUs 26 (43%).

Capillaroscopy, 40 (66%) patients had a pattern compatible with scleroderma.

Echocardiogram was performed in 58 patients (95%), in whom 8 patients (13%) presented (sPAP) > 40mmHg.

Chest CT was performed in 39 patients (64%), in whom 16/39 (27%) had ILD.

Anti-centromere antibodies were found in 35/57 patients (63%), ANA nucleolar antibodies in 9/57 patients (15%), Anti-Scl-70 antibodies in 6/40 patients (15%) and Anti-RNP antibodies in 5/45 patients (11%).

Treatment: phosphodiesterase type-5 inhibitor in 22 patients (36%), calcium inhibitor in 18 patients (30%), mycophenolate mofetil in 17 patients (28%), endothelin receptor antagonist in 4 patients (7%).

Conclusions: The most common clinical pattern was limited cutaneous scleroderma and clinical signs were RP and GERD with female predominance. An association was found between scleroderma pattern in the capillaroscopy and the presence of telangiectasias (p=0.038) and digital ulcers (p=0.027). The most common treatment was phosphodiesterase type-5 inhibitor.

137

USE OF BELIMUMAB IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: DRUG SURVIVAL AND FACTORS ASSOCIATED WITH ITS DISCONTINUATION

Lucila Garcia¹, Victoria Martire¹, Adriana Testi¹, and Garcia Mercedes¹. ¹Hospital San Martín La Plata, La Plata, Argentina.

Objectives: The aim was to investigate the cumulative survival of belimumab and to identify causes of drug discontinuation and associated factors in SLE patients.

Methods: An observational study was done in a Rheumatology Department. Medical records and drug infusion registry were used to obtain information on the patients. Inclusion criteria were SLE patients who fullfilled ACR 82/ SLICC 2012 classification criteria, older than 18 years of ageand who had received at least one dosis of belimumab in a period between January 2013 and August 2018. Parametric and non-parametric tests were used according to the type of variables. Variables related to the survival of Belimumab were analyzed in the Cox regression model and were used as time variables. The permanence of the drug as a dependent variable and different demographic, clinical or therapeutic factors as independent variables. P values less than 0.05 were considered statistically significant. Cumulative drug survival was evaluated by the Kaplan Meier curve.

Results: Fourty-one female SLE patients were included. Mean age of 43 years (SD±9.5) and mean disease duration of 16 years.

The most frequent manifestations for the use of belimumab were musculoskeletal and cutaneous disease, 46% and 34%, respectively. Belimumab was discontinued in 15 patients. Causes of discontinuation: Patient decision 26%, unavailability 33%, lack of response, pregnancy, neoplasm, adverse effects, remission and lost to medical follow-up 1%. No demographic, clinical and laboratory factors associated with drug discontinuation were found. Twenty-six patients continued on belimumab. Mean age of the first drug infusion was 40 years and median time of use was 12 months (QIR 8-25). The median cumulative drug survival was 57 months (CI 95% 16.5-97.4). Using multivariate regression Cox model, no association was found between drug discontinuation and other factors. Drug survival was 81%, 51%, 35% and 24% at 6, 12, 18 and 24 months.

Conclusions: Belimumab cumulative survival was 57 months. The main cause of discontinuation was drug unavailability followed by patient decision. No demographic, clinical and laboratory parameters were associated with drug discontinuation.

139

CARDIAC INVOLVEMENT IN ECUADORIAN SLE PATIENTS

Erika Palacios Santillán¹, and Fernando Naranjo Santos¹. ¹Hospital Eugenio Espejo, Quito, Ecuador.

Objectives: Establish the prevalence of heart involvement in patients with SLE, with or without associated APS at the Eugenio Espejo Hospital during theperiod from January 2015 to December 2017 and determine its association with traditional cardiovascular risk factors and SLE’s own risk factors.

Methods: Observational analytical epidemiological case-control study that included 109 patients from the Internal Medicine service of EEH.

Results: Cardiac involvement defined through electrocardiography and/or echocardiography was present in 65 patients with a prevalence rate of 59.6%. The most prevalent cardiac manifestations were: cavities enlargement (70.7%), valvular alterations (58.4%), and in third place pericardial disease (55.3%). Thrombocytopenia as a manifestation of SLE with or without associated APS was associatedwith the presence of cardiac involvement (OR 3.69; IC 95% 1.14-11.89, p= 0.02). A relationship between the presence of anti-cardiolipin aPL and thrombocytopenia could also be observed (OR 5.04, IC 95% 1.61-15.79, p= 0.003). Cardiac involvement in SLE was more frequent in patients with hypertension (OR 2.42; IC 95% 1.06-5.54, p=0.03) and those who were receiving betablockers (OR 6.56, IC 95% 1.41- 30.38, p=0.007) and anticoagulants (OR 5.05, IC 95% 1.38- 18.48, p=0.008).

Conclusions: Thrombocytopenia, hypertension, betablockers and anticoagulants treatment were associated with the presence of cardiac involvement. Thus, an initial and individual stratification of the risk is needed by conducting echocardiography which constitutes a non-invasive method, adequate for detecting cardiac abnormalitieseven in asymptomatic patients; also traditional risk factors as well as those associated with the disease itself need to be considered.

144

SURVIVAL ANALYSIS IN PATIENTS WITH LUPUS NEPHRITIS FOLLOWED UP AT A RHEUMATOLOGY CLINIC FOR A PERIOD OF 3 YEARS

Elias Fernando Rojas Báez¹, Marcos Aurelio Vázquez Báez¹, Gabriela Avila Pedretti¹, and Isabel Acosta Colmán¹. ¹Hospital De Clínicas San Lorenzo Paraguay, San Lorenzo, Paraguay.

Objectives: To determine remission/survival in patients with a diagnosis of lupus nephritis and factors associated with it.

Methods: Observational, longitudinal, analytical-cut study, which included patients with a diagnosis of lupus nephritis who achieved remission being followed at the Rheumatology service of the Hospital de Clínicas for a period of 3 years. To calculate the survival of the response to treatment, the Kaplan-Meier estimator was used, as well as the Cox regression model for the association analysis.

Results: A registry of 50 patients was obtained, 42 (84%) women and 8 (16%) men. The mean age was 29,44 years ± 9,48. The total response of lupus nephritis to induction therapy was observed in 84% of patients at 10,5 ± 12 months and relapse was observed in 32% at 22 ± 16.74 months. Of these 80% were women with an average age of 30,2 ± 9.7 years. Partial response was observed in 14%; 71% of them were women with an average age of 24,7 years. The reasons for relapse were treatment discontinuation, infection and irregular treatment in (8%, 8% and 6%, respectively). The median survival time of the induction treatment was 18,75 months. Regarding the factors associated with treatment survival, no significant differences were observed between men and women, the presence of anti-DNA antibodies, the use of methylprednisolone, immunosuppressive treatment and biopsy type.

Conclusions: A total nephritis response was found in most of the patients, with a mean treatment survival of 18.6 months; relapse was mainly due to treatment discontinuation and intercurrent infections. No association was found between treatment survival and other factors.

145

TREATMENT ADHERENCE AND HEALTH RELATED QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS FROM QUITO-ECUADOR

Andrea Cevallos¹, Heidi Fernández¹, Fernando Naranjo-Saltos¹, Ruth Jimbo Sotomayor², Diego Mera², and Gabriela-Carolina Guevara¹. ¹Hospital Eugenio Espejo, Quito, Ecuador, ²Pontificia Universidad Católica del Ecuador, Quito, Ecuador.

Objectives: Despite scientific advances, Systemic Lupus Erythematosus (SLE) continues to be an incurable disease with an unpredictable course that can considerably affect the health status of those who suffer from it and lead to disability. Therefore, since it is a chronic disease, problems surrounding the lack of treatment adherence and the evaluation of health-related quality of life (HRQoL) should be included in the state-of-the-art analysis for SLE.

Objective- Determine adherence to pharmacological treatment and health related quality of life in a group of 85 patients with SLE from Quito-Ecuador.

Methods: Prior authorization from the Human Research Ethics Committee for a descriptive, observational, cross-sectional study was obtained. The study was conducted in 85 patients with SLE at Eugenio Espejo Hospital in Quito-Ecuador. Sociodemographic and clinical variables of interest were collected and subsequently, treatment adherence with the Morisky scale was determined and the EuroQol 5D questionnaire for assessment of HRQoL was applied.

Results: The average age of the participants was 34.1 years. 39 patients (46%) were diagnosed with the disease between 1-5 years before this study took place. 77 patients (91%) did not present disease activity. 48 patients (56%) had comorbidities. The prevalence of polypharmacy was 56%. 60 patients (71%) did not get sufficientphysical activity. 48 patients had low treatment adherence (56%), 19 (22%) medium adherence and only 18 (21%) had high adherence. Patients self-assessed their health status, measured by the visual analogue scale, with an average of 76.6/100.

35% of the patients reported some problems with mobility and 5% described themselves as confined to bed. The self-care domain was better preserved, 87% reported no problems. 46% reported some problems on usual activities and 2% were unable to undertake them. 57% of patients described moderate or severe anxiety/ depression. The most affected domains of HRQOL, were pain and discomfort: 8 patients rated their pain as severe.

Conclusions: The evaluation of treatment adherence and HRQoL should be implemented as a strategy for the integral management in SLE. Our study, a pioneer in the field, showed that only 21% of patients had high adherence to treatment and that more than 65% reported moderate or severe permanent pain.

148

PRIMARY SJÖGREN SYNDROME AND DEVELOPMENT OF ANOTHER CONNECTIVE TISSUE DISEASE DURING FOLLOW-UP

Florencia Rodriguez¹, Anastasia Secco¹, Antonio Catalan Pellet¹, Natalia Herscovich¹, Cristina Amitrano², Cecilia Asnal², Alejandro Nitsche², Julia Demarchi³, Damian Duarte³, C Segura³, Francisco Caeiro⁴, Nadia Riscanevo⁴, Veronica Saurit⁴, Silvia Papasidero⁵, Carla Gobbi⁶, Paula Alba⁶, Laura Raiti⁷, Veronica Cruzat⁷, Lida Santiago⁸, Sofia Velez⁹, Gabriela Salvatierra¹⁰, and Vicente Juarez¹¹. ¹Hospital Bernardino Rivadavia, Capital federal, Argentina, ²Hospital Alemán, Buenos Aires, Argentina, ³Hospital Británico, Buenos Aires, Argentina, ⁴Hospital Privado De Córdoba, Córdoba, Argentina, ⁵Hospital Tornú, Buenos Aires, Argentina, ⁶Sanatorio Allende, Córdoba, Argentina, ⁷Clínica Bessone, Buenos Aires, Argentina, ⁸OMI, Buenos Aires, Argentina, ⁹Consultorio Privado S.V, Salta, Argentina, ¹⁰IPRI, Santiago Del Estero, Argentina, ¹¹Hospital Milagros De Salta, Salta, Argentina

Objectives: Primary Sjögren's Syndrome (pSS) is the connective tissue disease that is most frequently associated with other autoimmune disorders and approximately 30% of patients with SS have an associated autoimmune condition.

OBJETIVES: 1-Determine the frequency of patients who, following the diagnosis of pSS, developed another autoimmune rheumatic disease during their follow-up using the GESSAR database (Sjögren Syndrome Study Group of the Argentine Society of Rheumatology).

2-Detail the connective tissue diseases that occurred most frequently in these patients.

3-Describe the clinical, serological and salivary gland histology characteristics of these patients.

Methods: Descriptive, observational, cross-sectional study. We analyzed the data of patients diagnosed with pSS (American-European criteria 2002 / ACR-EULAR 2016), included in the GESSAR database. It was considered the development of another connective tissue autoimmune disease in those cases in which the diagnosis was added during follow-up.

Results: 681 patients were included, 94.8% were women, average age of 54(+/-14) and average age at diagnosis of 50(+/-13) years. 30(4.41%) developed another autoimmune rheumatic disease during their follow up. They were: Rheumatoid Arthritis 14, scleroderma 9, SLE 5, dermatomyositis 1 and rhupus 1. The mean age of this subgroup was 53(+/- 14), mean age at diagnosis of pSS 48(+/- 13). 91% were women. Regarding SICCA symptoms: 96% reported xerophthalmia, and 86.2% xerostomia. With respect to the objective tests: more than 80% had positive eye test, 81.2% positive sialometry, anti-Ro+ antibodies in 82.1% and anti-La+ antibodies in 33.33% of patients. 12/14 had a positive minor salivary gland biopsy. Prior to the diagnosis of RA, 78% presented with arthralgia and arthritis, 12 had RF+ and 2 anti-CCP+. Prior to the diagnosis of scleroderma, 44% had Raynaud's phenomenon and 22.22% were ANA positive with a centromeric pattern. Of the patients with the additional diagnosis of SLE, 1 had anticardiolipin antibodies and 100% reported arthralgia.

Conclusions: Of all the patients analyzed, 4.4% developed another connective tissue disease during their follow-up. We consider the importance of recognizing this possibility in order to arrive at an early diagnosis. The presence of certain clinical and serological manifestations could be considered as suggestive of the subsequent development of another autoimmune rheumatic disease.

149

PREVALENCE OF CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH SYSTEMIC SCLEROSIS

Victor Gustavo Martinez Aguero¹, Gabriela Avila¹, Marcos Vazquez¹, Margarita Gonzalez¹, Maria Teresa Filartiga¹, Osmar Centurión¹, Sonia Cabrera¹, and María Isabel Acosta¹. ¹Hospital De Clínicas, Encarnación, Paraguay.

Objectives: To describe cardiovascular and non-traditional risk factors in patients with systemic sclerosis and to identify the association of these with the presence of atheromatous plaques at the level of the carotid intima.

Methods: An observational, prospective cross-sectional study with an analytical component, carried out during the period between April and August 2018 in the Rheumatology Department of the Hospital de Clínicas. The clinical variables of cardiovascular risk were recorded as sex, age, smoking, blood pressure, abdominal perimeter, body mass index, family history, use of corticosteroids, toxic habits, use of statins and immunosuppressants, in addition to the clinical involvement of patients. All of them underwent a carotid Doppler echo as a screening of the presence of atheromatous plaques at that level.

Results: A total of 47 patients were included, 11 (23.4%) of them were men and 36 (76.6%) women, the mean age recorded was 49.78 ± 15 years; at the time of the study, there were no patients actively smoking, 8 (17%) were ex-smokers, the systolic pressure had average values of 115.87 ± 18 mmHg and the diastolic of 72.39 ± 13 mmHg, the average abdominal perimeter was 87.16 cm ± 11.6. The average body mass index was 25.59 ± 4.4 Kg / m2, 20% presented antibodies to anti-SCL-70.

Doppler ultrasonography of the carotids was performed in 16 patients with atherosclerotic plaques in 7 (43.75%) patients, of which 3 had plaques with clinical significance as well as association with the use of NSAIDs (p: 0.033), presence of anti SCL-70 antibodies (p: 0.002), anti-centromere (p: 000); no associations were identified with the other variables.

Conclusions: In this cohort, the presence of traditional and non-traditional CVR factors was observed. The use of NSAIDs and positivity for anti-SCL-70 autoantibodies was found to be related to the presence of atheromatous plaques in carotids by carotid ultrasound.

151

COMBINED IMMUNOSUPPRESSANT THERAPY IN REFRACTORY GRANULOMATOSIS WITH POLYANGIITIS

Goethe Salomón Sacoto Flores¹, Luis Felipe Flores-Suárez¹, and Natllely Ruiz¹. ¹Instituto Nacional de Enfermedades Respiratorias (INER) "Ismael Cosío Villegas", Ciudad De México, México.

Objectives: Case report. A 51-years old male was diagnosed in December 2015 with severe generalized granulomatosis with polyangiitis (GPA) due to ocular, ENT, pulmonary, musculoskeletal, renal, neurological, and cutaneous manifestations.

Methods: He was initially treated with methotrexate (MTX) 20 mg/week and oral prednisone (PDN) 1 mg/kg/day, achieving remission. One year later, while under MTX as maintenance treatment, he relapsed with identical symptoms. PDN 1 mg/kg/day and 6 intravenous cyclophosphamide (IV-CYC) pulses (1100 mg/pulse) were given. Despite treatment, pulmonary, cutaneous and renal symptoms persisted (BVAS 4).

Rituximab (RTX) 1g every two weeks for two doses was added with response. Cumulative PDN dose then was 14g. Nonetheless, five months later he developed new pulmonary nodules and active urinary sediment and was retreated with RTX as before. After improvement with lung nodules size reduction, they grew again 10 months later (BVAS 2). The decision was to combine both RTX and CYC as reinduction treatment.

Results: Two months later remission was achieved, and RTX has been continued for maintenance.

Conclusions: Combined treatment with RTX and CYC has demonstrated disease control in 96% of refractory cases at 6 months. The long-term evaluation of these strategies for both, induction and maintenance phases in conventional treatment-resistant cases, with the additional purpose to reduce the adverse effects by glucocorticoids, is still necessary.

152

MPO-ANCA POSITIVE SUBGLOTTIC STENOSIS IN A TAKAYASU ARTERITIS PATIENT. CASE REPORT

Goethe Salomón Sacoto Flores¹, Melissa Guadalupe Rodríguez Gonzalez², Natyelli Itzel Ruiz Gómez¹, Daniela Peralta Charpenel¹, Guillermo Perez Delgadillo¹, Luis Humberto Silveira Torres², and Luis Felipe Flores-Suárez¹. ¹Instituto Nacional de Enfermedades Respiratorias (INER) "Ismael Cosío Villegas"., Ciudad De México, Mexico, ²Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México.

Objectives: Case description.

Methods: A 43-years old female presented to us with a history of pericardial tuberculosis (TB) which was treated satisfactorily in 2009. During diagnostic workup elsewhere, upper limb pulseless disease was noticed, and she was diagnosed angiographically with a Numano IIB + P Takayasu arteritis (TA) which was treated with methotrexate and prednisone. Remission was achieved in 2012. In 2017 she developed a saddle-nose deformity, nasal discharge and crusts, and in 2018 was seen by an ENT specialist who confirmed biphasic stridor and a 7 mm diameter subglottic stenosis (SGS) which led to laser dilatation. Biopsies obtained showed chronic inflammation and scarring, with negative search for microorganisms.

Results: This case could be labelled as limited GPA according to clinical findings and positive ANCA serology, although not PR3-ANCA as most frequently seen. However, more cases with limited upper airways involvement have been reported being MPO-ANCA positive. Treatment with MTX and low-dose PDN continues as maintenance, as no progression of TA and no recent activity of the probable GPA has been documented.

Conclusions: Six cases of coexisting granulomatosis with polyangiitis (GPA) and TA have been reported. However, none previously had SGS as GPA manifestation. SGS presents in up to 25% of GPA patients. TB might explain SGS due to scarring, but the rinosinusal features and the positive serology, with resolution of the pericarditis after specific treatment, -thought but not proven to be by M. Tb with positive cultures-, leads to think this infection might not be the culprit of this patient’s ENT symptoms.

154

CLINICAL CHARACTERISTICS OF PRIMARY SJÖGREN'S SYNDROME IN ADULT PATIENTS DIAGNOSED AT AGE LESS THAN OR EQUAL TO 35 YEARS VERSUS THOSE OVER 35 YEARS OF AGE

Patricia Sasaki¹, Anastasia Secco¹, Antonio Catalán Pellet¹, Agustina Caceres¹, Nadia Riscanevo², Janet Flores², Francisco Caeiro², Cristina Amitrano³, Cecilia A. Asnal³, Alejandro Nitsche³, Carolina Segura Escobar⁴, Julia Demarchi⁴, Damian Duartes Noe⁴, Lida Santiago⁵, Laura Carmen Raiti⁶, Vanesa Cecilia Cruzat⁶, Carla Gobbi⁷, Silvia B Papasidero⁸, Sofia D. Velez⁹, Gabriela Salvatierra¹⁰, Vicente Juarez¹¹, and Paula Alba⁷. ¹Hospital B. Rivadavia, CABA, Argentina, ²Hospital Privado de Córdoba, Argentina, ³Hospital Alemán, CABA, Argentina, ⁴Hospital Británico, CABA, Argentina, ⁵OMI, CABA, Argentina, ⁶Clínica Bessone, Argentina, ⁷Hospital Allende de Córdoba, Argentina, ⁸Hospital Tornu, Argentina, ⁹Consultorio Privado S.V, Argentina, ¹⁰IPRI and Quorum Salud (Sgo del Estero), Argentina, ¹¹Hospital Milagros de Salta, Argentina.

Objectives: Although there is little information, the debut manifestations of primary Sjögren's syndrome in adult patients 35 years of age and younger include less pronounced Sicca manifestations and a high degree of systemic involvement.

Objective: To describe and compare the systemic manifestations, assessed through the domains of the ESSDAI and the glandular manifestations, in Argentinian adult patients 35 years of age and younger and those older than 35 diagnosed with primary Sjögren's Syndrome.

Methods: Cross-sectional observational analytical study. We analyzed the data of patients older than 18 years, with diagnosis of primary Sjögren's syndrome (American-European criteria 2002 / ACR EULAR 2016), included in the GESSAR database (Sjögren Syndrome Study Group of the Argentine Society of Rheumatology), with minus one control in the last 12 months. The presence of systemic manifestations assessed from the domains of the ESSDAI and the glandular manifestations, and as possible confounders were considered: sex, treatments and time of follow-up in years of each group.

Results: 665 patients were included. One hundred with an age at diagnosis ≤35 years, 92% of them women. Within the glandular manifestations, statistically significant differences were found between patients ≤35 years vs >35 years, in xerophthalmia (90.72% vs 95.64%, p= 0.04) and xerodermia (42.35% vs 57.36%, p=0.03). No significant differences were found in xerostomia or xerovagina. Statistically significant differences were found in the following domains of the ESSDAI: peripheral nervous system (4.05 vs 11.32, p=0.03), respiratory (6% vs 15.40%, p=0.01) and renal (6% vs. 1.59%, p= 0.02). No statistically significant differences were found in the glandular, joint, cutaneous, central nervous system, hematologicalor biological domains. In a subanalysis of the ESSDAI domains, significant differences were found in arthritis (37.37% vs 27.16%, p=0.04) and persistent dry cough (4.04% vs 11.47%, p=0.03). No significant differences were found in: female sex, follow-up time, symptomatic treatment, treatment with pilocarpine, hydroxychloroquine, corticosteroids or immunosuppressants.

Conclusions: A significantly lower frequency of xerophthalmia and xerodermia was observed in the group ≤35 years of age compared to those >35 years. Regarding systemic activity, less involvement of the peripheral nervous system and pulmonary domain and higher in the renal domain, with statistically significant differences were found in those ≤35 years of age. These results suggest a lower glandular compromise in patients diagnosed at a younger age, without a characteristic differential pattern in terms of systemic involvement.

155

RELATIONSHIP BETWEEN DISEASE ACTIVITY AND VITAMIN D LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS IN THE DOMINICAN REPUBLIC

Emelinda Tejada Reyes¹, Ingrit Mercedes Nuñez¹, Maria Marte Robles¹, Rorayma Jimenez Candelaria¹, Violeta Rosario¹, Roberto Muñoz Louis¹, Tirso Valdez Lorie¹, and Rafael Alba Feriz¹. ¹Hospital Docente Padre Billini, Santo Domingo, Dominican Republic.

Objectives: To determine the relationship between the activity of the disease with the levels of vitamin D in systemic lupus erythematosus patients from the Hospital Docente Padre Billini, between August - October 2017.

Methods: This was a longitudinal and analytical study, where we determine the levels of vitamin D and calcium in SLE patients who attended the Rheumatology clinic of the Hospital Docente Padre Billini, during the period August - October 2017. The activity of the disease was ascertained with the SELENA-SLEDAI scale.

Results: The study population was constituted by 53 patients, of whom, 50 fulfilled inclusion criteria; 92% were female. The most frequent age range was between ages 31 - 45 years. 46% of the patients were ethnic mulatto. 54% had a disease duration of less than 5 years. The most used treatment was chloroquine in 94%, followed by Glucocorticoids 88%. Calcium values were normal in 82% of patients. The vitamin D values were insufficient in 66% and deficient in 18% of the study population. When using Pearson's correlation coefficient to determine if there was any relationship between vitamin D levels and disease activity according to SELENA-SLEDAI, we found that there was no relationship between these variables. The SELENA-SLEDAI was in low activity of the disease in 74% of the patients. Only 2% (1) had a high activity of the disease, which had deficient levels of vitamin D.

Conclusions: In this study, the activity of the disease was not related to decreased vitamin D levels.

158

ROWELL SYNDROME. ABOUT A CASE

Candido Flores¹, Rocío Chávez Mejía¹, Guillermo Eduardo Ramírez García¹, and Rafael García Rascón¹. ¹Hospital Regional De Alta Especialidad Ixtapaluca, Ciudad De México, México.

Objectives: Introduction: Rowell syndrome is a rare entity that occurs mainly in middle-aged women and is characterized by the association of systemic lupus erythematosus (SLE) and erythema multiforme (EM) type lesions, with positive immunological markers such as antinuclear antibodies (ANA), anti-Ro antibodies and rheumatoid factor (RF) positivity.

Objective: To present a clinical case of Rowell's syndrome.

Methods: Case: A 36-year-old woman, without a relevant past medical history. began her clinical picture 6 months prior to admission; she presented photosensitivity and erythematous, scaly and pruritic lesions located on the anterior aspect of the right forearm and in the occipital region; for this she received unspecified topical antimicrobial treatment on multiple occasions. Quantified intermittent fever up to 40 °C was noted as well as extension of the lesions to the periungual regions of both hands with extension into the palms; painful papules in the initially affected regions and in forearms, face, ears and scalp, some presenting a central necrotic appearance ("target" image) developed. Patient also developed interphalangeal arthritis and arthritis in elbows and knees. During follow up she presented ulcers in the fundus of both ocular sacs, anal region, vulvar and oral cavity. Patient was admitted to the hospital where a a diagnostc work up was initiated, positivity was determined for anti-ribonucleoprotein antibodies, ANA 1:640 homogeneous, C3 22, C4 1.66, ESR 46, anti-Ro 17.35, anti-La> 2, MPO> 2, PR3 4.88.

Results: Discussion: Rowell's syndrome is a rare syndrome, in which patients with SLE develop lesions similar to EM, it is associated with the presence of ANA with mottled pattern, positive RF and anti-Ro antibodies. A fundamental characteristic in the diagnosis of EM is the non-association with markers of autoimmunity. Cutaneous manifestations are varied and may include erythema, papules, target lesions, vesicles, blisters and urticarial lesions, with major distribution in arms and legs. Management is focused on SLE, with the use of steroids as the first line. The therapeutic response and prognosis is similar to SLE, with variable response and recurrences.

Conclusions: Although Rowell syndrome is a rare and controversial entity, it should be suspected in patients with SLE and EM-like lesions where there is no evidence of a precipitating factor. This patient fulfilled classification criteria for mucocutaneous SLE and for Rowell's syndrome, for which treatment was adjusted with oral prednisone and topical betamethasone, hydroxychloroquine, azathioprine, with remission of symptoms.

161

CLINICAL CHARACTERISTICS OF PATIENTS WITH ANTI-TIF1-γ ANTIBODIES FROM THE REGISTRY OF INFLAMMATORY MYOPATHIES OF THE ARGENTINE SOCIETY OF RHEUMATOLOGY (SAR)

Yessica Maria Ponce Delgado¹, Ramiro Gómez², Andrea Braillard², Malena Viola³, María De la Vega³, Nicolás Pérez⁴, Graciela Gómez⁴, Amelia Granel⁵, and Óscar Rillo¹. ¹Hospital General de agudos Dr. I. Pirovano, CABA, Argentina, ²Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, C.A.B.A., Argentina, ³Hospital General de Agudos Dr. Cosme Argerich, C.A.B.A., Argentina, ⁴Instituto de Investigaciones Médicas "Alfredo Lanari”, Universidad de Buenos Aires, C.A.B.A., Argentina, ⁵Hospital de Gonnet de la Plata, Provincia De Buenos Aires, Argentina.

Objectives: Targoff et al. reported the presence of Myositis Specific Antibody, "Protein Intermediary Factor" (Anti TIF-1) in patients with dermatomyositis (DM), associated with neoplasia and dysphagia and present in approximately 20% of patients with DM1.

MAIN OBJECTIVE: To describe the clinical characteristics of patients with inflammatory myopathies (MI) and the presence of anti-TIF 1- γ antibody, from the MII Registry of the SAR.

Methods: A descriptive medical records review study that analyzed the sociodemographic data, clinical characteristics and presence of anti-TIF1γ of patients in the MII registry of the SAR. Antibodies were studied by linear immunoassay (LIA) and the reagent was funded through a grant by the New Projects Committee (CONUPRO), managed by the MI Study Group (GESAR) of the SAR.

Results: We studied 71 patients from the Argentinian Registry of MII of the SAR, of which 7% (5 patients) were positive for anti TIF 1- γ, with a median of 65 (24-73) years, predominantly female (4/5). Ethnicity (2 Amerindians and 3 Caucasians). All presented the typical characteristics of DM. One patient had an associated neoplasia (breast cancer), poor clinical outcome and died. Three patients presented swallowing disorders. The presence of positive antinuclear antibodies (ANA) (mottled nuclear pattern 1/80) was observed in 2 patients. Four patients received immunosuppressive doses of glucocorticoids and immunosuppressants.

Conclusions: We found similar data to what has been previously reported in the literature; however, a higher frequency of dysphagia was observed (1). Only one patient had an associated neoplasm, which presented a poor outcome. Despite the small number of patients studied, this is the first report of patients from Argentina with anti TIF1 γ antibodies.

BIBLIOGRAPHY: 1. Ueda-Hayakawa, et al. Autoantibody to transcriptional intermediary factor-1β as myositis-specific antibody: clinical correlation with CADM or DM with mild myopathy. Br J Dermatol.2018; DOI: 10.1111 / bjd.17098.

2. Naoki Mugii, et al. Oropharyngeal dysphagia in dermatomyositis: Associations with clinical and laboratory features including autoantibodies. Plos One. 2016; 11 (5).

164

DIAGNOSTIC PROCEDURES IN THE STUDY OF IDIOPATHIC INFLAMMATORY MYOPATHIES FROM THE ARGENTINIAN REGISTRY OF MYOSITIS

Graciela Gomez¹, Maria de los Angeles Gargiulo¹, Amelia Granel², Ana Marcos², Ramiro A Gomez³, Andrea Braillard Poccard³, Malena Viola⁴, María Celina De La Vega⁴, Cecilia N Pisoni⁵, Micaela Cossati⁵, Mariano Rivero⁶, Mariana M Aciar⁷, Mariela Crespo⁷, Carolina Costi⁸, Mercedes A García⁸, Maria N Lojo⁹, Verónica Wernicke⁹, Belen Barrios¹⁰, Silvia Papasidero¹⁰, Paula Girard Bosch¹¹, Rodrigo Garcia Salinas¹¹, Jessica Ponce¹², Oscar Rillo¹², Dafne Capelusnik¹³, Isabel Pineda¹⁴, Roberto Movia¹⁵, Boris Kisluk¹⁶, Guillermo Berbotto¹⁶, and Susana Visentin¹⁷. ¹Instituto De Investigaciones Médicas Alfredo Lanari, Ciudad Autonoma De Buenos Aires, Argentina, ²Hospital San Roque,Gonnet, La Plata, Argentina, ³Hospital de Clínicas José de san Martín, Ciudad de Buenos Aires, Argentina, ⁴Htal Cosme Argerich, Buenos Aires, Argentina, ⁵CEMIC, Buenos Aires, Argentina, ⁶Htal Británico, Buenos Aires, Argentina, ⁷Htal Ntro Señor del Milagro, Salta, Argentina, ⁸Htal San Martín, La Plata, Argentina, ⁹Htal Rossi, La Plata, Argentina, ¹⁰Htal Enrique Tornú, Buenos Aires, Argentina, ¹¹Htal Italiano, La Plata, Argentina, ¹²Htal Dr. Ignacio Pirovano, Buenos Aires, Argentina, ¹³Instituto de Rehabilitacion PsicoFisica, Buenos Aires, Argentina, ¹⁴Consultorio Privado, Venado Tuerto, Argentina, ¹⁵Hospital Evita, Lanus, Argentina, ¹⁶Htal Eva Perón, Granadero Baigorria, Argentina, ¹⁷Htal Durand, Buenos Aires, Argentina.

Objectives: The diagnosis of Idiopathic Inflammatory Myopathies (IIM) may be a challenge for the Rheumatologist and complementary studies may not be available in daily practice.

The aim of our study was to describe the frequency of complementary studies performed in the diagnosis of patients with IIM from the Argentinian Registry and to compare between the present time and 2 years before.

Methods: Adults with dermatomyositis (DM) and polymyositis (PM), according to Bohan & Peter criteria, and inclusión body myositis (IBM) were eligible from the Argentinian Registry of Inflammatory Myopathies. Sociodemographics, laboratory and complementary studies were analyzed from available medical records. A commercial kit for the study of specific myositis antibodies (MSA), Euroimmun, was bought through a grant from the Argentine Rheumatology Society. Descriptive statistics, Fisher test(p<0,05). Stata v.11.0 was used.

Results: Two hundred and sixty-four patients were analyzed, mean age at diagnosis was 45 ys ±15, women n=180 (68%). Ethnic groups: Caucasian 42%, mestizo 35% and Amerindian 9%. The majority of the patients came from public and private hospitals from Buenos Aires City and La Plata; only a minority came from Salta and Santa Fe Provinces. The frequency of diagnostic procedures available was:CK in 254 patients (p)(96%), ASAT: 242p (92%), ALAT 239p (90%), EMG:170p (65%),RMI 170p (64%),muscle biopsy 108p (41%), CT: 215p(81%), DLCO 97p(37%), ANA:242p (92%),MSAs: anti-Jo-1 in 229 p (87%),anti-PL7,PL12, SRP and Mi-2 in 169 p (64%). Anti NXP2, OJ, EJ, TIF1, and anti-SAE in 60p (23%).

Sixty per cent of patients had health insurance. Frequencies in diagnostic methods were similar when they were compared with the first report of our Registry, although there was an increased in the access to MSA.Patients with health insurance had better access to muscle biopsy (p<0,001) and MRI (p<0,025) and electromyography (p<0,001).

Conclusions: - CK, ANA, anti-Jo-1 and Chest CT scan were done in more than 80% of the patients.

- Muscle biopsy was performed at a very low frequency: less than 30% of the patients.

- MSAs were available because of a grant from the Argentine Rheumatology Society.

- The accessibility to diagnostic techniques is heterogeneous and essential diagnostic procedures such as MRI, MSAs and muscle biopsy are difficult to obtain in our country.

165

RETINAL TOXICITY DUE TO HYDROXYCHLOROQUINE IN A SINGLE CENTER SYSTEMIC LUPUS ERYTHEMATOSUS COHORT

Yesid Jovanni Portilla Villarreal¹, Ramiro Gomez¹, Diana Dubinsky¹, Sheila Leal Castro¹, Diego Marino¹, and Yuly Cuellar¹. ¹Hospital De Clínica San Martín, Caba, Argentina.

Objectives: To evaluate ocular toxicity from HCQ in patients with SLE

Methods: Our electronic SLE database (Jan 2014-June 2018) was searched. Patients fulfilling ACR 1997 criteria, withat least 1-year of follow-up, at least 12 week of HCQ treatment, who had a computerized visual field (CVF)study and who had discontinued HCQ due to retinal toxicity (RT) were included. Patients who had discontinued HCQ for other reasons (intolerance, hypersensitivity, muscular toxicity, skin rash) were excluded.

RT was defined as a decreased in visual acuity and/or worsening in CVF below reference levels that required HCQ discontinuation or dose adjustment.

Other possible causes of retinal abnormalities (diabetes, arterial hypertension), cumulative dose of HCQ at the time of its discontinuation, time of HCQ exposure and damage accrual as per the SLICC-DI at the time of HCQ discontinuationand at the last recorded visit were assessed.

Results: 231 patients were evaluated. 33 were included. 10 (30%) reinitiated treatment at a later time, in 5 of them with dose adjustment. HCQ discontinuation was definite in 23 (69.7%, 9.9% of the global population).

Patients with RT had mean age 44.5 (SD±12,6) years; Ethnicity: Amerindian 6,06%, Caucasian 6,06% and Mestizo 87,8%; 12 (36.3%) had arterial hypertension and 2 (6.06%) had diabetes.

Median cumulative dose of HCQ at the time of its discontionuation was 576 gr (IQR 144-1008). 9 (27.2%) patiens had a cumulative dose >1000 gr and 13 (39.3%) had >5 years of exposure.

Mean SLICC-DI at HCQ discontinuation was 0.8 (DS±1,2) and 1,17 (SD±1,7) at the last visit.

22 (70.9%) patients with CVF worsening were receiving HCQ >5 mg/kg (real weight) and 23 (74.1%) were receiving HCQ >6.5 mg/kg (ideal weight)

Year/Kg <1000 >1000

<5 20/33(60,6%) 0

>5 4/33(12,1%) 9/33(27,2%).

Conclusions: We observed a similar frecuency of HCQ discontinuation due to RT as reported in other studies. In our patients, there was no difference in RT between patients receiving <5 mg/kg (real weight) vs <6.5 mg/kg (ideal weight).

We found a higher frecuency of RT in patients with a cumulative dose of HCQ <1000 g and <5 years of HCQ exposure. These data may challenge the American Society of Ophthalmology’s recommendation of performing CVF after 5 years of exposure or >1000 g of cumulative dose.

An increment in the SLICC-DI score was observed after HCQ discontinuation, reaffirming the role of HCQ therapy in SLE.

167

CLINICAL AND IMMUNOLOGICAL CHARACTERISTICS OF 175 PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS, QUITO - ECUADOR

Mariela Mascote Márquez¹, and Fernando Naranjo-Saltos¹. ¹Hospital Eugenio Espejo, Quito, Ecuador.

Objectives: To determine the initial clinical, immunological and epidemiological characteristics of 175 patients diagnosed with Systemic Lupus Erythematosus (SLE) of the Eugenio Espejo Hospital and to associate the SLEDAI-2K activity index at the onset of the disease with manifestations and complications.

Methods: Through an observational, descriptive and cross-sectional study, we analyzed the sociodemographic, clinical and immunological variables of patientsmeeting the 2012 SLICC criteria, being cared for by the Internal Medicine Service of the Eugenio Espejo Hospital during the 2015-2017 period. The variables were collected from the electronic file or system of medical records of the hospital, in a previously protocolized format, having been approved by the Ethics Committee in Human Beings Research.

Results: We studied 175 patients with SLE: 160 women and 15 men, with a female:male ratio 10.6:1, the average age of diagnosis was 29.3 ± 9 years, 87% were of mixed ethnicity. The most frequent clinical manifestations were hematologic 100%, musculoskeletal 69.7%, renal 56.6%, general 50.9% and mucocutaneous 47.4%. Deep vein thrombosis, haemoptysis and palpitations were frequent in men. 92% had ANA and positive anti-ds-DNA, followed by low C3 and anti-Sm with 64% and 57.4%, respectively. The mean SLEDAI-2K score was 11.7 ± 6.5 and 61.1% of the patients had severe activity at the time of diagnosis. There was an association between severe activity and proteinuria, lower limb edema, seizures, headache, arthritis, alopecia, leukopenia and lymphopenia. Nephrologic complications occurred in 56% of the patients (lupus nephropathy IV and III), followed by infections in 49.1% and neuropsychiatric manifestations in 22.9%.

Conclusions: The present study demonstrates how the clinical and immunological characteristics of this group of patients with SLE of the Eugenio Espejo Hospital are similar to those exhibited in other international studies. More than half of the patients had an elevated SLEDAI-2K index at disease onset, which translates into the severe involvement that patients receive from the health care systems in Quito-Ecuador.

168

ANTIBODIES AGAINST INSULIN

Hugo Javier Madariaga Charaja¹, Rafael Salas¹, and Ascuña Valery¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To present the case of a diabetic patient with antibodies against insulin who improved with adjuvant immunosuppressive therapy.

Methods: Case report.

A 57-year-old woman, type 2 diabetic, under treatment with insulin lispro associated with NPH insulin for 3 years. Because of poor glycemic control she was changed to basal boluses with insulin glargine every 24 hours and insulin glulisine 3 times a day. She maintained good glycemic control for two years, with periodic dose escalation. Empaglifocin was added. One year before presentation, and despite an adequate dose of insulin, glycemic levels did not go below 300 mg/dl. Anti-insulin and anti-GAD antibodies were dosed, being positive in 2.9 and in 0.3 respectively. We also studied thyroid profile, ANA, Anti-DNA, anti-Sm, Anti-Ro and Anti-La, results were normal and negative, respectively.

Results: Immunosuppressive treatment was started with Azathioprine 100 mg/day and Deflazacort 30 mg/day, but glycemia persisted high. Treatment was switched to methotrexate 22.5 mg weekly and deflazacort 30 mg/day (until its discontinuation in 4 months), in addition to insulin glargine associated with glulisine. Patient presented 3 episodes of hypoglycemia, so the dose of insulin had to be decreased, currently with good response, sustained glucose control in values ​​lower than 160 mg / dl for more than six months.

Conclusions: - In patients with diabetes treated with insulin who do not achieve a good control the disease despite adequate insulin dosage, it is important the consider the presence of anti-insulin antibodies.

- Use of immunosuppressive therapy proved to be effective in this patient with diabetes mellitus treated with insulin who developed anti-insulin antibodies.

169

IG G4-RELATED OCULAR DISEASE (IG G4-ROD)

Hugo Javier Madariaga Charaja¹, Valery Ascuña¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To describe the clinical-epidemiological characteristics of patients with a recent diagnosis of Ig G4-related ocular disease (IgG4-ROD).

Methods: All patients diagnosed for the first-time with Ig G4-ROD and who were cared for at the rheumatology and ophthalmology services of Hospital III Yanahuara, Arequipa- Perú, over the last two years were included.

Results: A total of 6 patients were included, 5 (83%) were females, median age at presentation 44 ± 14 years, minimum age atpresentation 29 years and maximum 77 years. The median time of illness prior to diagnosis was 0.7 months. 100% presented proptosis, restriction of eye movements, conjunctival hyperemia and decreased visual acuity, which was bilateral in 2 patients. The diagnosis was made by elevated serum Ig G4 in all patients and histopathological confirmation in 4 (67%). All patients had excellent clinical response to systemic steroids, 1 patient received treatment with methotrexate and 5 patients with rituximab. In all patients, proptosis resolved, and visual acuity wasrecovered.

Conclusions: - Orbital inflammatory disease is an ocular manifestation of Ig G4-related disease, being a frequent manifestation in our series with respect to other series.

- The response to immunosuppressive treatment is effective and prompt, especially with rituximab.

170

IgG4-RELATED DISEASE IN HOSPITAL III YANAHUARA, AREQUIPA, PERU

Hugo Javier Madariaga Charaja¹, Maria Elena Luza¹, Carola Cervera¹, Brissette Soto¹, and Valery Ascuña¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To describe the most frequent clinical manifestations and response to treatment of Ig G4-related disease in our environment.

Methods: All patients with the first-time diagnosis of Ig G4-related disease who were cared for at the rheumatology and ophthalmology services of Hospital III Yanahuara over the last four years were included.

Results: There was a total of 10 patients with this diagnosis. 80% were female. The most frequent clinical manifestation was Orbital Inflammatory Disease (60%) followed by Recurrent Parotiditis (40%). Ninety percent of patients had elevated IgG4 serum levels and histopathological confirmation in 40%, all of them with inflammatory orbital disease, the latter are classified as definitive cases, while the other 60% are classified as probable cases.

All patients had an excellent response to systemic corticosteroids and treatment with Rituximab (90%) and Azathioprine (10%). In 100% of patients with orbital involvement, proptosis resolved, and visual acuity improved. And in 75% of the parotiditis there was total resolution.

Conclusions: The most frequent presentation was the orbital. All had a good response to treatment with systemic corticosteroids associated with Rituximab in 90% and Azathioprine in 10%.

60% of cases could not be classified as definitive because there are still technical difficulties for taking a biopsy and there are no expert pathologists in our country to evaluate this disease.

171

INFLAMMATORY MYOPATHY SECONDARY TO BEVACIZUMAB

Hugo Javier Madariaga Charaja¹, and Valery Ascuña¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To present a case of inflammatory myopathy secondary to bevacizumab, because of its rare presentation.

Methods: Case presentation.

A 64-year-old woman diagnosed with cervical cancer, with metastases to the pelvis, stage III A according to IFGO (International Federation of Gynecology and Obstetrics), under oncological treatment of bevacizumab 1000 mg, carboplatin 400 mg, paclitaxel 200 mg for 17 months. In addition, medical history of motor sensitive axonal polyneuropathy in lower limbs treated with pregabalin 225mg / d for 15 months.

Results: She presents pain and progressive muscular strength reduction 4/5 of extensor muscles of the neck, thighs and calves. Total CPK: 1134, Electromyography informs Myopathy and muscle biopsy confirms inflammatory myopathy.

Conclusions: Bevacizumab is a drug widely used in cancer. In patients with pain and loss of muscle strength, although infrequent, inflammatory myopathy should be considered as an adverse effect.

174

TREATMENT WITH HUMAN IMMUNOGLOBULIN IN PATIENTS WITH REFRACTORY INFLAMMATORY MYOPATHY TO RITUXIMAB

Hugo Javier Madariaga Charaja¹, Maria Elena Luza¹, Brissette Soto¹, Carola Cervera¹, and Valery Ascuña¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To describe the clinical characteristics and therapeutic response of patients with a diagnosis of inflammatory myopathy refractory to treatment with Rituximab.

Methods: Three cases of patients with a diagnosis of inflammatory myopathy refractory to first-line treatment and with a good response to human immunoglobulin (IVIG), treated at Hospital III Yanahuara Arequipa-Peru over the last 4 years are included.

Results: Case 1: 57-year-old male with polymyositis, received treatment with Methotrexate and Rituximab plus steroids. CK persisted elevated from 310 to 490 u/L.IVIGwas indicated: 2 g/kg/month associated with prednisone 10 mg/day. From the fourth month until the present time CK has remained normal without the use of corticosteroids.

Case 2: A 52-year-old woman with autoimmune necrotizing myositis. Was treated with Methotrexate, and subsequently withRituximab plus steroids. CK persisted elevated from 670 to 978 u/L. Subsequently, IVIG 2 gr / kg was given monthly. At the second month of treatment, CK was 98; it has continued within normal limits until the present time.

Case 3: 46-year-old male with dermatomyositis. He was treated with Cyclophosphamide, Methotrexate, Azathioprine, Mycophenolate, Rituximab monotherapy and Rituximab plus mycophenolic acid and steroids. This treatment normalized the total CK for a few weeks and then the CK raised again (CK: 389-1025 u/L). IVIG was given 2 gr / kg monthly. At the third month the CK was 102 u / L, and it is still normal 6 months later.

Conclusions: - IVIG showed efficacy in achieving remission in patients with inflammatory myopathy refractory to conventional treatment and rituximab.

- If it was not for its high cost, IVIG could be the treatment of choice in cases of myopathies refractory to immunosuppressants, before Rituximab or in the future, it could become the treatment of choice.

180

SYSTEMIC LUPUS ERYTHEMATOSUS AND CARDIOVASCULAR RISK. TRADITIONAL AND NON-TRADITIONAL FACTORS

Karin Baumann¹, Nelson Ortiz¹, Johnatan Losanto¹, Marcia Melo¹, Sonia Cabrera¹, Gabriela Avila¹, Teresa Filartiga², Ma. Isabel Acosta¹, and Osmar Centurion¹. ¹Hospital De Clínicas. Universidad Nacional, Asunción, Paraguay, ²Laboratorio Curie, Asuncion, Paraguay.

Objectives: Patients with Systemic Lupus Erythematosus have an increased cardiovascular riski due to the proinflammatory state of the disease which leads to increased morbidity and mortality.

Objective: Describe the cardiovascular risk factors in patients with Systemic Lupus Erythematosus.

Methods: Materials and methods: An observational cross-sectional study was conducted based on a survey in which cardiovascular risk variables were explored. The study included patients diagnosed with Systemic Lupus Erythematosus receiving their care at the Department of Rheumatology of the Hospital de Clínicas of the National University of Asunción from January to December 2018. The preliminary results of this project, supported by the Conacyt (l Prociencia 2015 grant, are now presented.

Results: Forty-three patients were included, of whom 95.3% were female and 4.7% male, with an average age of 31.7±9.4 years; 86% of the patients were from the metropolitan area; only of 35% of the patients had secondary education. Most patients (74%) were single; having 1.2 ± 1.4 children on the average.

Family history of hypertension was observed in 69.8%, diabetes 34.9% and dyslipidemia in 41.9% of the cases. Among the traditional risk factors were sedentarism in 74.4%, arterial hypertension in 27.9%, smoking in 11.6% and dyslipidemia in 9.3% of the patients. Patients had an average body mass index of 25.4 ± 5.8. Among the non-traditional risk factors renal involvement was found in 55.8% of the patients, antiphospholipid syndrome in 6.9% and the use of corticosteroids in 44.2% of the patients with a mean daily dose of 13.4mg.

As to the activity of the disease, patients had an average SLEDAI of 3.04±3.38.

Conclusions: Traditional and non-traditional risk factors were observed in patients with Systemic Lupus Erythematosus studied in the LUPUS PARAGUAY cohort. It is important to act in a timely manner on non-traditional cardiovascular risk factors and to create awareness in our patients of the importance of reducing traditional risk factors, so as not to add more cardiovascular risk than that of the activity of the disease.

183

CHARACTERIZATION OF A SINGLE CENTER SYSTEMIC LUPUS ERYTHEMATOSUS COHORT ACCORDING TO COMPLEMENT LEVELS

Sheyla Leal Castro¹, Luis Orlando Roa Perez¹, Sandy Sapag Duran¹, Adriana Seewald¹, Jaime Andres Betancourt Lopez¹, Yesid Jovanni Portilla Villarreal¹, and Diana Dubinsky¹. ¹Hospital De Clínicas José de San Martín, Ciudad Autónoma Buenos Aires, Argentina.

Objectives: Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which inflammation is mediated by complement activation, immune complex deposition which lead to damage. Consumption of C3 and C4 complement fragments is accepted as a disease activity marker.

The aim of this study is to describe the clinical and serologic characteristics of SLE patients according to complement levels.

Methods: Our SLE electronic database was examined (Jan 2014-Aug 2016). We included patients ≥18 years, fulfilling ACR 1997/SLICC 2012 classification criteria, with at least one-year of follow-up and at least two complement levels determinations at different times during their follow-up.

Patients were classified in 4 groups, defined as following: Group 1 (normal C3 and C4 on all determinations), Group 2 (C3 and C4 below reference levels on all determinations), Group 3 (only C4 below reference levels on all determinations) and Group 4 (C3 and/or C4 on variable levels, with at least one determination below reference levels).

Demographic data, disease activity by SELENA-SLEDAI, damage accrual by SLICC-DI, presence of anti DNAds and anti Sm antibodies and clinical manifestations were assessed.

Statistical analysis was performed using Epi info v7. Correlation was assessed using χ or Fisher´s test as appropriate.

Results: 149 patients were included. 95.3% female, mean age at diagnosis was 30.6 years (CI: 28,5 – 32,8), mean disease duration 9.7 years. Mean SLICC-DI by group: Group 1: 1.0, Group 2: 0.5, Group 3: 1.3 and Group 4: 0.6. All groups with hypocomplementaemia showed a higher SLEDAI than Group 1 (p=0.0013).

Anti-dsDNA and anti-Sm were higher in groups with hypocomplementemia (p=0.01 and p=0.0001 respectively). As to the clinical manifestations, a significant difference was found in Lupus Nephritis (Group 1, 36.8%, Group 2, 44.1%, Group 3 78.6 % and Group 4, 36,4 % (p=0.0002)) and hemolytic anemia (Group 3, 28.6% and Group 1, 17.6 % (p: 0.0196)).

Conclusions: An association between C4 persistently below reference levels (Group 3) and anti-dsDNA antibodies and Lupus Nephritis was found. Group 3 patients may have a worse prognosis due to renal involvement.

Complement levels during follow up could be used as a marker to assess nephritis risk in SLE patients.

188

ACHIEVING REMISSION AND LOW DISEASE ACTIVITY IN LUPUS: A CHALLENGE IN VENEZUELA

Yurilis Fuentes-Silva¹, Armando García¹, Manuel Anés¹, Irama Maldonado², Carlota Acosta², Luisa del Valle Ortega, Carlos A Rondón M³, Eylen Camargo⁴, Mayra Rauseo², and Martín A Rodríguez^5,6. ¹Universidad de Oriente, Ciudad Bolívar, Venezuela, ²Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Venezuela, ³Hospital de Clínicas de Ceciamb, Puerto Ordaz, Venezuela, ⁴Hospital Central de San Cristóbal, San Cristóbal, Venezuela, ⁵Policlínica Metropolitana, Caracas, Venezuela, ⁶Centro Nacional de Enfermedades Reumáticas, Servicio de Reumatología, Hospital Universitario de Caracas, Caracas, Venezuela.

Objectives: Over the last several years many lupus patients in Venezuela have been with limited or no access to medications and under poor healthcare conditions due the current humanitarian crisis. The shortage or total absence of antimalarials and corticosteroids and the majority of immunosuppressants have been going on for quite some time but getting even worse since 2018. The regular use of medication is of paramount importance for an adequate control of disease activity and prevention of organ damage in lupus patients. In this study we have evaluated remission and LLDAS in Venezuelan patients with SLE and examined their correlation with medication availability and compliance.

Methods: From August to December 2018, 216 patients with SLE were evaluated; all patients fulfilled the 1997 ACR or the 2012 SLICC criteria. All patients signed an informed consent. We collected socio-demographics and related disease data: age, gender, education, occupation, disease duration, SLEDAI, SLICC-Damage Index. The remission state was assessed by the Definition of Remission in SLE (DORIS), LLDAS and non-optimally controlled (NOC) patients. We used dichotomous variables for medication compliance. Non-compliance time was investigated (< 3 months and ≥ 3 months). Statistical analysis was done using Chi square, Fisher´s exact test and Student's t-test for dichotomous and continuous variables, respectively. P-values of < 0.05 were considered statistically significant.

Results: 216 patients with SLE were included; 94% were female, mean age was 40.3±13 years, mean disease duration was 9.6±7.9. Patients mean education (years) was 13.1±3.9. Mean SLEDAI and SLICC-DI were 3.2±5.1 and 0.4±1.1, respectively; patients fulfilled criteria for remission in 42%, LLDAS in 65% (N=140) and NOC in 35% (N=76). Patients have been prescribed antimalarials, corticosteroids, immunosuppressants and biological agents in 95%, 62%, 47% and 0.9%, respectively. Medication non-compliance ≥3 months was 75%, 70% and 34.7% for immunosuppressants, antimalarials and corticosteroids, respectively. LLDAS and NOC groups were comparable for gender, age, education, occupation and disease duration. Lupus activity and number of hospitalizations during the previous six-month period were both significantly higher in NOC vs. LLDAS group (p<0.00001 and p=0.0001, respectively). There was a lower antimalarial treatment compliance in the NOC vs. the LLDAS group (p=0.01).

Conclusions: A high proportion of patients were non-compliant to prescribed medications mainly due to their unavailability in our country. However, the proportion of patients in LLDAS was higher than those in NOC. It is possible that the accumulated benefit of a previous regular therapy may have protected patients in the last few years of medication unavailability. Further work is warranted.

189

SYSTEMIC SCLEROSIS: DESCRIPTIVE ANALYSIS OF AN AMBULATORY COHORT

Yesika De León¹, Adriana Solari¹, Gabriel Maciel¹, Sandra Consani¹, Carolina Díaz, and Jorge Facal. ¹Hospital Maciel, Montevideo, Uruguay.

Objectives: To describe the clinical characteristics, specific auto-antibodies pattern and morphological changes in nailfold-video capilaroscopy in ambulatory systemic sclerosis (SSc) patients from Maciel Hospital.

Methods: Descriptive, observational, cross-sectional study.

Information was obtained from clinical records of patients with the diagnosis of SSc according to the 2013 EULAR/ACR criteria being care for at the Autoimmune Diseases Ambulatory Clinic, Maciel Hospital, between 2001 and 2017.

Patients were classified according to their clinical manifestations.

Data were collected in an Excel spreadsheet and expressed in absolute values, percentages and means.

Sex, clinical spectrum, skin and visceral involvement, antibody profile and morphological changes in nailfold video-capillaroscopy were recorded. A restrictive respiratory defect was diagnosed with restriction pattern on spirometry, reduction in DCLO and typical images in High resultion Chest CT (HRCT). Pulmonary arterial hipertension was estimated by Doppler echocardiography.

Gastroesophageal involvement was considered in patients with gastroesophageal reflux symptoms and/or compatible findings in upper endoscopy, esophageal manometry or barium esophagram.

Results: 68 patients with SSc. 65 (95.59 %) women. 3 (4.41%) men. Median age at diagnosis: 48.2 years. 3 patients with incomplete records were excluded.

Raynaud’s phenomenon was the most frequent first symptom (73.5%).

Clinical spectrum: limited SSc 33 (48.5 %), diffuse SSc 13 (19.1 %), preSSc 14 (20. 5 %), SSc sine scleroderma 4 (5.8 %), early SSc 4 (5.8%).

Clinical involvement: sclerodactyily 45 (66.1 %), puffy fingers 5 (7.3 %), Raynaud’s 66 (97 %), digital ulcers 6 (8.8 %), pitting scars 9 (13.2 %), calcinosis cutis 2 (2.9 %), telangiectasias 32 (47 %).

Gastroesophageal reflux: 32 (47 %).

Respiratory involvement: pulmonar artery hypertension 9 (13.2 %), insterstitial lung disease 11 (16.1 %).

Renal involvement: scleroderma renal crisis 1 patient.

Auto-antibodies: 56/68 performed: Results: anticentromere: 21, Scl-70: 12, negative antibodies: 25.

Nailfold video-capillaroscopy: 43/68 performed, pathologic 37/43 (86%).

Conclusions: Limited SSc was the most frequent clinical presentation. We found similar clinical features and auto-antibody profile as described previously. The disease was more prevalent in females, with Raynaud’s phenomenon, skin and esophageal involvement as common manifestations.

Pulmonary involvement was frequent in our cohort (near 1/3 patients). Sclerodermic renal crisis was extremely uncommon (perhaps due to the use of angiotensine-converting enzyme inhibitor treatment).

We emphasize the importance of early diagnosis and close patients’ follow up. This should allow physicians to diagnose early visceral involvement and begin individualized treatment in order to improve the patient’s prognosis.

192

TEMPORAL ARTERY BIOPSY: HISTOPATHOLOGICAL DESCRIPTION AND CLINICAL CORRELATION IN 59 TEMPORAL ARTERY BIOPSIES

Diego Andrés Marino¹, Yesid Jovanni Portilla¹, Ramiro Adrian Gomez¹, and Diana Dubinsky¹. ¹División de Reumatología, Hospital De Clínicas "José De San Martín", Ciudad Autónoma de Buenos Aires, Argentina.

Objectives: Primary objective: describe the histopathological characteristics of temporal artery biopsies (TAB) performed in patients with clinical suspicion of Giant Cell Arteritis (GCA).

Secondary objective: describe the clinical characteristics of patients suspected of GCA in which TAB was performed, evaluate a possible association between histopathological characteristics and clinical characteristics in these patients.

Methods: Descriptive, historical study. TAB performed in our center, a terciary university hospital in Buenos Aires, to patients with clinical suspicion of GCA between May 30th, 2005 and Feb 13th, 2017 were identified from the records of the Pathology service and included in this report. Histopathological characteristics were examind.

The clinical records of these patients were reviewed and epidemiological data, clinical characteristics (systemic symptoms, polymyalgia rheumatica, cranial symptoms and ischemic symptoms), laboraroty data (hematocrit, haemoglobin, white blood cell count, platelet count and ESR) and glucocorticoid dose at the time of TAB were analyzed.

Statistical analysis was performed using Epi Info v.7.22. A p<0.05 was considered significant.

Results: 59 TAB were included. The mean length of the biopsied samples was 19,8±9mm. 90% of the TAB were unilateral and 85% of them were performed under glucocorticoid treatment (mean dose 46,7±26.9 mg/day).

In 20% of the TAB, the histopathological diagnosis was GCA. In those, inflammatory infiltrate 100% (12/12) with a lymphocytic predominance, giant cells 100% (12/12), internal elastic disruption 33% (4/12) and granulomas 16% (2/12).

Mean age at time of TAB 70±12 years; male:female ratio was 1:2.9. 33% (10/30) had TAB compatible with GCA (TAB+).

Systemic symptoms 43% (13/30), and cranial symptoms 60% (18/30). Comparing TAB+ and TAB- patients, systemic symptoms were present in 60% vs 35%, cranial symptoms in 80% vs 50%. None of these characteristics was statistically significant.

Comparing TAB+ and TAB- patients mean ESR was 82±39 vs 64±41 mm/h. None of these parameters was statistically significant.

No association was found between clinical characteristics and histopathological characteristics.

Conclusions: In our study, only 20% of TAB met the diagnosis of GCA. However, most patients were under glucocorticoid treatment at the time of TAB and the mean length of the samples was 19 mm.

We did not find any difference in clinical manifestations or laboratory parameters in TAB+ vs TAB- patients nor any association between clinical characteristics and histopathological characteristics.

200

MYCOPHENOLATE MOFETIL AS INDUCTION TREATMENT IN LUPUS NEPHRITIS: A REAL-LIFE STUDY

José Maximliano Martínez Pérez¹, Rafael Lopez¹, Andres Zuñiga¹, Genesis Maldonado¹, Mario Moreno Alvarez¹. ¹Hospital Luis Vernaza, Guayaquil, Ecuador.

Objectives: Mycophenolate mofetil (MMF) is frequently used as an alternative treatment for lupus nephritis (LN). The results of global studies suggest good response in Latin American patients. The main objective of our study was to evaluate the response to 6-months induction treatment with MMF in moderate to severe LN. Secondary objectives were the improvement of 24h proteinuria, renal SLEDAI (rSLEDAI), serum creatinine and serum albumin.

Methods: We performed an analysis of patients treated with MMF as induction treatment for active LN between January 2009 and March 2018 in the rheumatology service at a teaching hospital in Guayaquil, Ecuador. Patients without treatment adherence were excluded from the analysis. Lack of adherence was defined as not taking continuous medication for at least 2 weeks. Demographic, clinical, laboratory and renal biopsy data were obtained from the electronic clinical history (ECH). Good response to treatment excluded patients who died, those needing rescue therapy, those developing end-stage renal disease due to LN or those not achieving a a 25% decrease in proteinuria g/24 h at the end of the induction treatment.

Results: Twenty-six patients received MMF, 21 were included. 95.2% (20/21) women; mean age 31.18y; time elapsed from diagnosis to LN 0.9 years. 100% were Hispanic. At the beginning 71.4% had low C3, 61.9% low C4, 81% had positive anti-DNA antibodies; and the median eGFR 83.36 ml/min/1.73m². The average dose of MMF was 1.5±0.40 g with a median treatment duration of 6.10 months. Primary objective was reached in 95.2% (20/21) (Cochran's Q 40.00, p <0.001).There was a decrease in rSLEDAI (10.47 ± 2.97 vs 3.61 ± 3.07; p <0.0001), proteinuria g/24h (2.22 vs 0.48 IR, p<0.0001), albumin (3.44±0,53 vs 3.96±0.30, p<0.0001) g/dl and C3 (59.00 vs 91.0, p<0.0046) mg/dl. eGFR was stabilized (83.36 vs 90.12, p=01452) ml/min/1.73m². Prednisone dose was significantlyt reduced (29.97 vs. 12.85 p<0.0001) mg/d. Only 8 (38%) patients had a renal biopsy; three class III and IV each and two class V. Adverse events occurred in 8 patients (38,1%); 75% (6/8) UTIs, one pneumonia, one pulmonary TB and two herpes zosters.

Conclusions: In our study of Latin American patients treated with MMF doses for real-life LN induction therapy we were able to demonstrate a good response. The number of patients and the lack of access to renal biopsy limit this study but we believe it is important to show the real-life data of a hospital in Latin America.

207

RISK FACTORS RELATED TO NEOPLASMS IN HISPANIC PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Luis Velásquez¹, Jhirly Mercado¹, Alberto Cabello-Castillo^1,2, and Yurilís Fuentes-Silva¹. ¹Universidad de Oriente, Ciudad Bolívar, Venezuela, ²Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Venezuela.

Objectives: A predisposition for developing neoplasms has been described in patients with systemic lupus erythematosus (SLE). This could be related to the SLE pathological process and/or associated factors such as comorbidities, treatments and associated viral infections. The aims of this study is to report the frequency of both benign and malignant neoplasms in patients with SLE and to investigate the risk factors related to them.

Methods: From August 2016 to October 2018, 155 patients with diagnosis of SLE (according to SLICC 2012) were evaluated. We investigated socio-demographic data: gender, age, education, occupation, body mass index (BMI), smoking and caffeine habits, age at menarche, hormone replacement therapy (HRT), oral contraceptive (OC) use, family history of neoplasm. We also studied variables related to SLE and possible comorbidities such as SLE duration, comorbidities, all treatments for SLE used since its diagnosis. Patients were divided into two groups: those patients who developed neoplasms (NG) and those who did not or controls (CG). All patients signed an informed consent. Statistical analysis was done using Chi square, Fisher's exact test and Student's t-test for dichotomous and continuous variables, respectively. p-values of <0.05 were considered statistically significant.

Results: NG (N=31) and CG (N=124) groups were comparable regarding gender, ethnicity, BMI, education, smoking status, caffeine use, OC use, age at menarche, HRT, a positive family history of neoplasm, positivity of ANA and anti-DNA and complement levels. Patients in the NG group were significantly older than the CG (44.3±13.9 vs. 38.9±13.1, p=0.02). Disease duration was significant longer in the NG vs. the CG (15.5±11.5 vs. 9.1±7.6, years, p=0.0001). We observed neoplasm in 20% of patients, only 5% was represented by malignancies. Main malignancies were breast, uterus and ovarian cancer. Pack-years index and cumulative dose of corticosteroid were significant higher in the NG than in the CG (p=0.02 and p=0.001, respectively). Regarding SLE treatment, mycophenolate was prescribed more frequently in the CG than in the NG (88.7% vs. 11.3%, p=0.015). The diagnosis of neoplasms was done prior to SLE onset in 37.5%, at the time of SLE presentation in 12.6% and after SLE onset in 46.9%.

Conclusions: We observed certain risk factors for neoplasms in SLE population: advanced age, longer disease duration, higher pack-year index and cumulative dose of corticosteroids. The majority of neoplasms appeared after SLE diagnosis. The more frequent neoplasms in this population were on the breast and uterus. Mycophenolate mofetil presented a possible protective effect for the development of neoplasms; further studies on this topic are warranted.

209

POOR HRQOL AND FATIGUE ARE ASSOCIATED WITH A HIGHER WORK PRODUCTIVITY IMPAIRMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS

Cristina Reátegui-Sokolova^1,2, Rocío Gamboa- Cárdenas¹, Mariela Medina-Chinchón¹, Francisco Zevallos¹, Paola Zeña-Huancas¹, Claudia Elera-Fitzcarrald^1,3, Víctor Pimentel-Quiroz¹, José Alfaro-Lozano¹, César Pastor-Asurza^1,4, Risto Perich-Campos^1,4, Zoila Rodríguez-Bellido^1,4, Graciela S. Alarcón^5,6, and Manuel Ugarte-Gil^1,3. ¹Hospital Nacional Guillermo Almenara Irigoyen, Lima, Perú, ²Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud - Universidad San Ignacio de Loyola, Lima, Perú, ³Universidad Científica del Sur, Lima, Perú, ⁴Universidad Nacional Mayor de San Marcos, Lima, Perú, ⁵Universidad Peruana Cayetano Heredia, Lima, Perú, ⁶University of Alabama at Birmingham, Birmingham, Estados Unidos.

Objectives: To determine the factors associated with absenteeism (percentage of the time missed from scheduled work-time over the preceding 7 days, due to SLE), presenteeism (percentage of time from scheduled work-time where productivity was impaired while patient is at work, over the preceding 7 days, due to SLE) and overall work impairment (combination of absenteeism and presenteeism) in patients with SLE.

Methods: A total of 133 consecutive (1997 American College of Rheumatology (ACR) criteria) working patients with SLE were assessed between October 2017 and December 2018, using a standardized data collection form. Sociodemographic, disease and work-related variables were collected. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); disease damage with the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI); health-related quality of life was assessed with the LupusQoL and fatigue with the FACIT. Work Productivity and Activity Impairment (WPAI) was assessed with the respective questionnaire; absenteeism and presenteeism due to overall health and symptoms during the past 7 days were scored. Linear regression models were performed to determine the factors associated with absenteeism, presenteeism and overall work impairment. Potential factors included were age at diagnosis, gender, socioeconomic status, educational level, SLEDAI, SDI, FACIT and the components of the LupusQoL.

Results: The mean age at diagnosis was 32.2 years (11.8); 121 (91.7%) were female. Nearly all patients were Mestizo. Mean years of education was 14.1 (2.6). The mean disease duration was 11.9 (7.5) years. Mean SLEDAI was 2.9 (4.0), and mean SDI was 1 (1.4). The mean percent of time for absenteeism was 5.0 (12.9), 28.5 (26.4) for presenteeism, and 31.3 (27.2) for overall work impairment. In the multiple regression analysis, factors associated with absenteeism were disease duration (B=-0.34; SE=0.12; p=0.007); pain (B=-0.14; SE=0.06; p=0.046); intimate relationship (B=-0.07; SE=0.03; p=0.046) and emotional health (B=0.16; SE=0.06; p=0.006), with presenteeism were physical health (B=-0.43; SE=0.14; p=0.002) and FACIT (B=-0.87; SE=0.30; p=0.005) and with overall work impairment were pain (B=-0.40; SE=0.11; p=0.001) and FACIT (B=-0.74; SE=0.28; p=0.010).

Conclusions: A poor HRQoL and a higher level of fatigue were associated with a higher percentage of absenteeism, presenteeism and overall work impairment in SLE patients. Addressing the factors related to HRQoL and Fatigue may have significant impact on work performance among SLE patients.

210

HIGH INCIDENCE OF OSTEOPOROTIC FRACTURES IN A SINGLE COHORT OF 700 PATIENTS WITH SYSTEMIC SCLEROSIS

Marília Sampaio-Barros¹, Adriana Bortoluzzo¹, Henrique Carriçoda Silva¹, Ana Paula Luppino-Assad¹, Danieli Andrade¹, Rosa Maria Pereira¹, and Percival Sampaio-Barros¹. ¹Universidade De São Paulo, São Paulo, Brazil.

Objectives: The aim of this study was to describe the frequency of symptomatic osteoporotic fractures in a large Brazilian cohort of patients with systemic sclerosis (SSc) and to analyze the clinical and laboratory parameters associated with their occurrence.

Methods: Methods: This is a medical records review study analyzing the diagnosis of osteoporotic fractures in the setting of acute pain complaint referred by 700 SSc patients who were being care for at a single SSc outpatient clinic in Brazil from 2010 to 2018. There was predominance of females (87.4%), white ethnicity (65.9%) and limited SSc (51.3%). Clinical, demographic and laboratory data were obtained from an electronic register database. Univariate and multivariate analysis were performed to eamine the factors associated with the occurrence of fractures. Statistical significance was considered when p<0.05.

Results: Among 700 SSc patients, 83 patients (11.9%) were diagnosed with at least one symptomatic osteoporotic fracture. Patients with osteoporotic fractures, when compared with those without fractures, were older (67.72+11.94 vs. 54.12+13.69 years; p<0.01) and were also older at disease onset (50.98+12.51 vs. 41.20+13.92 years; p<0.01) and at diagnosis (53.22+13.10 vs. 34.34+14.02 years; p<0.01); they also had a longer disease duration (16.81+9.24 vs. 12.92+9.32 years; p<0.01). In the female patients, age at menarche and age at menopause were similar in the two groups. Osteoporosis (OP) was significantly associated with female gender (p=0.014), limited SSc subtype (p=0.049), calcinosis (p=0.007), gastric involvement (p=0.043), pulmonary hypertension (p=0.042), and cancer (p=0.016). Regarding the specific SSc autoantibodies, there was statistical trend between OP with fractures and anticentromere (p=0.079) and anti-Scl70 antibody (p=0.068). Multivariate logistic regression showed that female gender (OR=3.296; 95%CI 0.988-10.993; p=0.052), alder age at onset (OR=1.088; 95%CI 1.064-1.114; p=0.012) and longer disease duration (OR=1.088; 95%CI 1.058-1.119; p=0.014) were associated with the occurrence of symptomatic OP fractures.

Conclusions: The frequency of symptomatic OP fractures was high in a large Brazilian SSc cohort, affecting predominantly older female patients in the setting of specific clinical manifestations.

211

METABOLIC SYNDROME IN THE PRIMARY ANTIPHOSPHOLIPID SYNDROME

Paula Alba¹, Maria Mercedes Vigliano¹, Carla Andrea Gobbi², Carla Maldini¹, Gustavo Pepe², Marcela De Marchi¹, Viviana Neme¹, Eduardo Horacio Albiero¹, and Marcelo Augusto Yorio¹. ¹Catedra de Semiologia. UHMI 3 UNC, Cordoba, Argentina, ²Catedra de Clínica Médica. UHMI 3 UNC, Cordoba, Argentina.

Objectives: Background: Metabolic Syndrome (MS) is highly prevalent in rheumatic diseases and it is recognized as a new independent cardiovascular risk factor. Objective: to study the frequency of MS in patients with Primary Antiphospholipid Syndrome (APS).

Methods: We studied patients with APS according to the Sydney Criteria at the Rheumatology Unit at a Cordoba Hospital from May 2014 to July 2018; a control group matched for age and gender was also studied. Clinical and demographic data were analyzed. Sera samples were tested for lipid profile, glucose, insulin level (IN), TSH, free T4, uric acid, and autoantibodies. MS was defined by 3 different criteria: World Health Organization (WHO), Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF). p < 0.05 was considered statistically significant

Results: 80 patients were included, 71 females, with a mean age of 36 years and 80 as a control group, 71 females with mean age of 34.5 years. Weight, abdominal waist (AW) and BMI were 70.87 kg, 91.81 y 26.78 in APS patients and 70.11 Kg, 85.32, 25.95 in the control group. (p=0.76, p=0.001, p=0.36). Glucose level CT, HDL, LDL, and TG were 100.8, 176.6, 57.16, 109.8, 103.4 in APS patients and 99.5, 188.4, 63.62, 115.6, 94.9 in the control group (p=0.43, p=0.02, p=0.002, p=0.25, p=0.43). 12.5% of APS patients had MS according to OMS criteria and 16.7% according to ATPIII and 17.5% according to IDF definition and 8.8% of control group had MS according to OMS criteria, 13.3% according to ATPIII and 10% according to IDF definition (p= 0.44, p= 0.20, p= 0.16)

Conclusions: A higher frequency of different components of the MS was found in APS patients and there is a tendency according to IDF definition. MS is a known risk factor for cardiovascular disease, morbidity and mortality in systemic autoimmune diseases. A tight control of this condition in the early stages of the disease should be recommended.

215

FREQUENCY OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RELATIONSHIP WITH ACTIVITY OF THE DISEASE AND ACCUMULATED DAMAGE

Carolina Segura Escobar¹, Pedro Arbey Quevedo Mayorga, Cecilia Zaffarana, Demarchi Julia, Andrea Gomez, Guillermo Bartel, Geoffredo Earsman, Silvia Papassidero, and Andres Caicedo. ¹Hospital Británico De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina.

Objectives: To determine the frequency of ANCA in patients with SLE and to investigate if there are differences in the activity of the disease and the accumulated damage between ANCA positive and vs. ANCA negative patients.

Methods: Observational cross-sectional study. We included patients diagnosed with SLE according to the SLICC / ACR 2012 criteria, aged ≥18 years, treated at two rheumatology services of Buenos Aires recruited in the period from February to August 2018, and in whom the presence of ANCA by IFI and from PR3 and MPO by ELISA were available. Sociodemographic, laboratory and disease characteristics were collected from the medical records. The Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SLICC) scores were assessed at the time of enrollment into the study. Statistical analysis: Descriptive statistics. Student’s t test, Mann Whitney, Chi square and Fischer exact test.

Results: Thirty-six patients were included. 30 (83.3%) were women, 6 (16.6%) were men. The median age at diagnosis was 41.1 years (SD: 13.83), the median disease duration time was 7.6 years (SD: 5.95). There were 4 ANCA positive patients (11.1%); ELISAs were performed in 3 of them all being positive for MPO, none for PR3. When comparing those ANCA (+) vs ANCA (-) patients: The median age in years was 46.25 (SD: 5.61) vs. 40.46 (SD: 14.46) p=NS; the median diseas duration time was 12.25 (SD: 4.64) vs. 7 (SD: 5.9) years, p=0.03; the median of the SLEDAI score was 6 (SD: 6.92) vs. 4.09 (DS: 5.77) p=NS. The median SLICC Damage Index was 1.5 (SD: 2.38) vs 0.25 (SD: 0.76) p=NS; CRP values were high in 3 of the 4 the ANCA group (+) (75%) vs 8 (25%) p=0.028.

Conclusions: -11.1% of the study population was positive for ANCA, all of them with specificity for MPO.

-The variables associated with ANCA positivity in the univariate analysis were longer disease duration and a higher frequency of elevated CRP.

-Although the SLEDAI and SLICC-Damage Index scores in ANCA (+) patients were higher but this difference was not statistically significant.

-No significant differences were found between the groups in terms of sex, ethnicity, comorbidities, renal compromise or antiphospholipid syndrome; likewise, there were no differemces in laboratory parameters such as: Complete blood cell count, complement, proteinuria, renal function, or the presence of antibodies to DNA, Ro, La, Sm, RNP or Antiphospholipid.

218

LUPUS NEPHRITIS: ANALYSIS OF REBIOPSIES AND EVOLUTION

María Cecilia Argento¹, Maria Florencia Martinez¹, Juan Pablo Ruffino¹, Ariana Ringer¹, Nadia Cuadranti¹, Ignacio Rolla¹, Carla Achilli¹, Juan Vandale¹, Martin Baldomir¹, María Soledad Constantini¹, María Noel Cortese¹, Mariano Palatnik¹, Julieta Milanesio¹, Graciela Rombo¹, Ruben Darío Cavoduro¹, Marcelo Abdala¹, and Liliana Monje¹. ¹Hospital Provincial Del Centenario, Rosario, Argentina.

Objectives: To describe the clinical, anatomopathological and therapeutic characteristics of patients diagnosed with lupus nephritis (LN). To identify rebiopsies, the reasons that lead to this practice and histological changes.

Methods: Observational, descriptive and medical records review study. Patients from the Centenario Hospital, Rosario, Argentina, diagnosed with LN by renal biopsy for a period of 39 years (1978-2017) were included. Information was obtained from a database. Clinical, histological and therapeutic data was analyzed. The WHO classification of 1975 modified in 1982/1995 and subsequently the ISN / RPS classification of 2003 were used to describe histological findings in renal biopsies.

Results: 108 patients were included (90% women,10% men) Mean age: 29 years. Clinical presentations: 60% arterial hypertension, 45% nephrotic syndrome, 29% nephritic + nephrotic, 17% asymptomatic urinary disorder (AUD), 8% nephritic syndrome and 2% rapidly progressive renal failure. LN types:11.1% type II; 9.2% type III; 62% type IV; 12% type V and 2.7% mixed III + V. 38 rebiopsies were obtained from 34 patients. There were histological changes in 37%: 4 (10.5%) progressed from non-proliferative to proliferative and 7 (18.4%) from proliferative to non-proliferative. Most frequent change: from type IV to V. Reasons for rebiopsy: 30 cases of nephrotic syndrome, 7 of nephritic syndrome and 1 of AUD. Induction treatment: Cyclophosphamide (CP), Mycophenolate mofetil (MMF) and plasmapheresis. Maintenance therapy: Azathioprine 51%, MMF 32.4% and CP 13.8%. Evolution: 41.6% presented some type of remission (30.5% complete remission), 23% chronic renal failure; 11% were transplanted, 3% required hemodialysis and 18.5% died.

Conclusions: LN is an important predictor of morbidity and mortality. The transformation of renal lesions from one histological class to another occurs between 10-50% of the cases. Despite new therapeutic options, remission is achieved in 50-70% of patients and 10-20% progress to terminal chronic kidney disease within the ensuing5 years. In our study, 31.5% required renal rebiopsy, with a histological change in 37% of them and 29% progressed from non-proliferative to proliferative forms and vice versa. Renal rebiopsy is invaluable to assess the courseof kidney lesions due to SLE and to define treatment.

224

FUNCTIONAL IMPAIRMENT AND QUALITY OF LIFE IN PATIENTS WITH SYSTEMIC SCLEROSIS

Irma Dolores Reyes Banegas^1,2, José Anibal Chacón Súchite^1,2, Eva Griselda García^1,2, Roberto Carlos Morales^1,2, Lisseth Angélica Rodas Escobar^1,2, and Abraham García Kutzbach^1,2. ¹Asociación Guatemalteca Anti Enfermedades Reumáticas (AGAR), Guatemala, Guatemala, ²Universidad Francisco Marroquín (UFM), Guatemala, Guatemala.

Objectives: To determine the health status and quality of life in patients with systemic sclerosis (SS). To describe the demographic features of patients with SS. To describe the capillaroscopic findings in patients with SS.

Methods: We perfomed a descriptive cross-sectional study in which we reviewed sociodemographic - clinical characteristics, and quality of life, using a validated instrument. We performed a capillaroscopy exam, scored the modified Rodnan, the HAQ- DI (Health Assessment Questionnaire Disability Index) in patients being cared for at the AGAR clinic from August 2012 to October 2018. Inclusion criteria: Patients with diagnostic criteria for Systemic Sclerosis according ACR and EULAR, aged 18 to 90 years. Exclusion criteria: Localized Sclerosis or morfea, sclerodermiform syndromes.

Results: Thirty patients were included, mean age 58 years. 97% were female, 77% were housewives. The SS subtypes were: limited SS 77%, and difuse SS 33%. We found 30% of Overlap: Sjögren syndrome in 20%, RA in 10%. The mean time of disease duration was 5 years. The current treatment of patients was: DMARDs 80%, NSAIDs 66%, Steroids 26%.

The musculoskeletal, mucocutaneous and gastrointestinal clinical manifestations were the most common findings. The Rodnan modified score showed a slight skin thickening in most cases 76.6%. The HAQ-DI score was 2.03 SD 0.68. 56% of the patients had moderate to severe functional impairment.

The capillaroscopic findings showed: sclerodermiform pattern 22 (73.3%), normal pattern 2 (13.3) and tortuous pattern 2 (6.6%)

Conclusions: This study shows the important role of evaluating n the quality of life through the HAQDI. Likewise, it demostrates the importance of knowin more in detph the variability on capillaroscopic patterns and their correlation with the modified Rodnan score. All these variables can be predictive of disabling impairment in patients with systemic sclerosis.

228

EXPOSURE TO ENVIRONMENTAL FACTORS IN SYSTEMIC SCLEROSIS: DISTINCT DEMOGRAPHIC PATTERN AND ASSOCIATION WITH MYOPATHY AND PIGMENTARY DISTURBANCES

Lisbeth Aguila¹, Henrique Carriço da Silva¹, Ana Cristina Ribeiro¹, Ana Paula Luppino-Assad¹, Danieli Andrade¹, and Percival Sampaio-Barros¹. ¹Universidade de São Paulo, São Paulo, Brazil.

Objectives: To identify environmental factors in a large cohort of patients with systemic sclerosis (SSc) examining their clinical and laboratory presentation.

Methods: A cohort of 662 patients being cared for at a single Brazilian SSc outpatient clinic was examined regarding environmental factors, including organic solvents, silica, pesticides, silicone implants and cocaine. Clinical, demographic and laboratory data were obtained from an electronic register database.

Results: The cohort consisted in 662 patients, with a predominance of females (87%), white ethnicity (66%) and limited SSc (50.8%), with a mean age of 52.4 (+14.2) years; 28.6% had positive anti-Scl70 and 25.4% anticentromere antibodies (ACA). Of them, 70 patients (10.6%) had known previous exposure to environmental factors. Organic solvents (51.4%), silica (20%), silicone (12.9%) and pesticides (11.4%) were the most frequent exposures. The group with positive environmental exposures was more likely to be of males (40% vs 10%; p<0.001), of non-Caucasian ethnicity (47.1% vs 32%; p=0.014), being previous or current smokers (48.6% vs 32.3%; p=0.007) and had a shorter disease duration (11.6+9.8 vs 13.7+9.3 years; p=0.01). Most clinical features, including disease presentation, organ involvement, capillaroscopic and serologic findings were similar between the groups. Remarkably, the exposure group had a higher frequency of myopathy (25.7% vs 14.5%; p=0.015) and pigmentary disturbances (22.9% vs 13.5%; p=0.036). After multivariate analyses, only previous exposure to environmental factors (p=0.015) and shorter disease duration (p=0.007) remained associated with myopathy.

Conclusions: This study showed that SSc patients with previous exposure to environmental factors are demographically distinct, probably due to occupational exposure, and present a higher frequency of myopathy and pigmentary disturbances.

239

CLINICAL AND IMMUNE CHARACTERIZATION OF PATIENTS WITH PRIMARY SJOGREN’S SYNDROME

Carlos Arteaga¹, Nancy Barrera¹, Natalia Prieto¹, Yeimy Trujillo¹, and Philippe Chalem¹. ¹Fundación Instituto De Reumatología Fernando Chalem, Bogotá, Colombia.

Objectives: Characterize a cohort of patients with primary Sjogren's syndrome in the center of Rheumatology in Bogota, Colombia.

Methods: All samples were processed for ANA and anti-dsDNA by Indirect Immunofluorescence assay (IFA) in the automated HELIOS system, then ELISA tests were performed in the automated SQ2 system. All the results were confirmed with a second specific test. The reagents were from AESKU DIAGNOSTICS.

Results: The clinical characterization included age, diagnostic time, gender, eye symptoms, Conjunctival tumor, Oral symptoms, xeroderma, and recurrent parotitis.

The prevalence was higher in women than in men. Disease duration was on average 65 months. The main symptom was the ocular manifestations of dry eye, followed by xerostomia; the main systemic involvement was pulmonary involvement, with the presence of isolated bronchiectasis. Only about half of the patients presented clinical arthritis. No patient was found to be anti-DNA antibodies positive. Most of the samples were positive for SSA antibodies with fine speckled pattern by ANA. The prevalence of Anti-Alpha Fodrin IgA antibodies was higher than IgG.

Conclusions: It is possible to make an association between clinical manifestations and serological profiles. In general, the presence of autoantibodies correlates with age of onset, female predominance, increased risk of organ involvement, and the presence of other antibodies.

240

ALL-CAUSE HOSPITALIZATIONS IN ARGENTINIAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Natalia Andrea Perrotta¹, Maria Jose Lopez Meiller¹, Veronica Malah¹, and Diana Dubinsky¹. ¹Hospital De Clínicas José De San Martín, Ciudad Autónoma De Buenos Aires, Argentina.

Objectives: Systemic lupus erythematosus (SLE) has a bimodal mortality pattern, first peak: 20 years (relapses and infections) and a second later (cardiovascular diseases).

Hospitalization rate varies between 8.6 and 18.9% per year, up to 56% in two years. Hospitalizations for SLE flare: 11% to 80.8% and infectious causes of hospitalization: 10.9% to 37%. Other causes: cardiovascular disease, venous thromboembolism, associated autoimmune diseases, morbidity associated with pregnancy, complications due to accumulated damage and adverse drug reactions.

In this work we study the causes of hospitalization of patients with SLE admitted to a hospital in the Ciudad Autónoma de Buenos Aires, Argentina.

Methods: Review all patients with SLE admitted to Hospital de Clinicas Jose de San Martin, Ciudad Autónoma de Buenos Aires, Argentina, between January 2014 and December 2017.

Inclusion criteria were ≥16 years at the time of hospitalization and patients meeting the SLICC 2012 classification criteria.

Patient demographics, cause for hospitalization and medication lists, SLEDAI 2K and co-morbid conditions.

Descriptive statistics were obtained using standard statistical methods, with means (S.D.) and median (I.Q. R.) used for continuous variables and percentages used for other variables.

Statistical analyses were done using Epi Info version 7.2.2.2. Independent-samples t-test analysis was performed to identify differences in means for continuos variables, Fisher's exact test using two tailed was used to analyze two dichotomous variables. p<0.05 was considered statistically significant.

Results: 121 hospitalizations (72 patients). F:M ratio 5. 25/72(34.7%) patients had more than one hospitalization and 32/121 admissions had more than one cause of hospitalization: 164 reasons.

Average age at admission: 40 years (SD:16.43). Duration of the disease between diagnosis of SLE and admission median of 5 years (range 0-35 years). At the time of admission: median SLEDAI 5 (range 0-27).

Flare: 86(52.4%): renal (34,8%). Infection, 44/164(26.8%): urosepsis 12/44(27.3%), pneumonia 11/44(25%). Uncommon causes: 28/164 (17%). Cardiovascular diseases: 6/164 (4.96%). Patients hospitalized for flare compared with other causes were younger (mean 35 (S.D.13.9); p<0.0017) and had a shorter disease duration (median 3.5 (IQR:1-7); p<0.0017).

The duration of hospitalization was 16.52 days (S.D.15) in patients with flares vs 11.75(S.D.8.9) days for other causes; p<0.03.

Intensive care unit (ICU): 17/121 hospitalizations (14.05%), median hospitalization time was 24 days (IQR;14-30) compared to 10 days (I.R.5-15.5) for those who were not admitted to the ICU; p <0.008.

3(2.48%) died: sepsis, obstetric and cardiogenic shock.

Conclusions: The main cause of hospitalization was flare (52.4%) which is in agreement with the literature. These patients were younger with a shorter disease duration.

The number of hospitalizations for infections was higher than in developed countries. This difference could be explained: use of different prevention strategies, lower socioeconomic level, less access to health systems, different hospitalization criteria and ethnic factors.

Cardiovascular diseases have been a rare cause of hospitalization. Possibly due to our patients’ disease duration time; thus there is greater disease activity and use of immunosuppressants, less dyslipidemia and less accumulated time of corticosteroids use.

246

CLINICAL CHARACTERISTICS OF HOSPITALIZED ECUADORIAN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH EMPHASIS IN INTENSIVE CARE UNIT

Andrés Zúñiga Vera^1,2, Marietrini Kelly García Peñafiel², Génesis Denisse Mera Chapi², Rafael López Martínez^1,2, José Martínez Pérez¹, and Mario Moreno Álvarez^1,2. ¹Hospital Luis Vernaza, Guayaquil, Ecuador, ²Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador.

Objectives: To describe the clinical characteristics of patients with Systemic Lupus Erythematosus (SLE) admitted to the Luis Vernaza Hospital (HLV), with emphasis on Intensive Care Unit (ICU). To relate the ICU admissions and mortality with the intensity of the flares by SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index) score.

Methods: A cross-sectional study was conducted in patients admitted to HLV between 2015-2017. The protocol of the RELESSER (Spanish Rheumatology Society Lupus Registry) cohort was followed from health records. Descriptive analysis were used for demographic and clinical variables, Pearson correlation test was used to relate SLEDAI-2K with ICU admission and mortality.

Results: 83 patients with SLE were admitted. 88% were women, age ranged between 15 and 24 years. Main clinical manifestations were: serological (88%), hematological (87%), renal and articular (both with 76%). Renal manifestations: proteinuria and cellular casts (65%), lupus nephritis (54%) and hematuria and pyuria (53%), 22% of patients progressed to renal failure. Hematological manifestations: non-hemolytic anemia (61%), lymphopenia (59%), leukopenia (40%) and thrombocytopenia (34%). Serological findings were: low complement (71%), antiDNA (58%), ANA Western Blot (57%), and antiphospholipid antibodies (54%).13% had antiphospholipid syndrome. Severe manifestations in patients admitted to the ICU were: lupus nephritis (76%), thrombocytopenia and renal failure (52%), valvular dysfunction and pleuritis (41%), psychosis and cardiomyopathy (38%). 8% of patients died during their hospitalization; 86% from the the ICU. ICU admission and SLEDAI score had a correlation of 35% and demise with SLEDAI score a correlation of 19%.

Conclusions: The most common clinical manifestations were serological, hematological, renal and articular. There was a very low positive correlation between the SLEDAI score and mortality and a low positive correlation between admission to the ICU and the SLEDAI score.

247

NEUROPSYCHIATRIC LUPUS: ANALYSIS OF AN ECUADORIAN COHORT

Rafael Ignacio López Martínez¹, José Martínez Pérez¹, Andrés Zúñiga Vera¹, and Mario Moreno Álvarez¹. ¹Hospital Luis Vernaza, Guayaquil, Ecuador.

Objectives: The aim of this study was to examine the clinic characteristics, management and outcome of systemic lupus erythematosus (SLE) patients with neuropsychiatric manifestations (NPM).

Methods: A cross-sectional study was conducted. SLE patients admitted between 2014 and 2018 to a high complexity hospital because of a disease flare and who also presented related NPM were included. Demographics data, clinical presentation, treatment and laboratory variables were recorded. Descriptive statistics were performed for data analysis.

Results: Twenty SLE patients with NPM were studied, 90% were women, mean age 26,57 years, time from diagnosis to NPM 0,35 years. Clinical manifestations: Nephritis 90%, skin involvement 65%, lymphopenia 60%, arthritis 55%, serositis 55%, leukopenia 20%, alveolar hemorrhage 15%, thrombocytopenia 15%, oral ulcers 15% and AHA 5%. Laboratory: ANA 100%, anti-DNA antibodies 90%, low complement 95%. anti-Sm 40%, anti-Ro 25%, anti-La 10%, anti-RNP 30%. Mean SELENA - SLEDAI score was 26,20. NPM: seizure 70%, acute confusional state 45%, cognitive dysfunction 20%, psychosis 10%, peripheral neuropathy 10%, myelopathy 5% and CVD 5%. Abnormal EEG 60%. MRI was normal in 20%, 35% had small punctate hyperintense lesions (HL) and 45% had extensive HL. All patients received IV methylprednisolone; immunosuppresors 55% -CYC (10/20), MMF (1/20), RTX 45%, IVIG 20% and plasmapheresis 10%. Combination treatment was necessary in five cases. Mortality rate was 5%. Alive patients recovered their neurologic condition after 6 months of being discharged from the hospital.

Conclusions: NP involvement is an early SLE complication during the course of a highly active and generalized disease. Despite the severity of the NPM, the functional prognosis is good, and the mortality seems to be low, if a wide therapeutic arsenal, multispecialty staff and necessary infrastructure are available.

252

COMPARISON OF SLICC AND EULAR/ACR CLASSIFICATION CRITERIA FOR SYSTEMIC LUPUS ERYTHEMATOSUS IN TWO MULTIETHNIC COHORTS

Guillermo Pons-Estel¹, Manuel F. Ugarte-Gil², Guillermina Harvey³, Daniel Wojdyla³, Russel Griffin⁴, Verónica Saurit⁵, Enrique R. Soriano⁶, Eloisa Bonfa⁷, Loreto Massardo⁸, Mario H. Cardiel⁹, Luis M. Vilá¹⁰, Rosana Quintana¹, Graciela S. Alarcón¹¹, and Bernardo A. Pons-Estel¹. ¹Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina, Rosario, Argentina, ²Universidad Científica del Sur, Lima, Perú, ³Universidad Nacional de Rosario, Argentina., Rosario, Argentina, ⁴Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, Estados Unidos, ⁵Hospital Privado Universitario de Córdoba, Córdoba, Argentina, ⁶Servicio de Clínica Médica, Instituto Universitario, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, ⁷Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil, ⁸Centro de Biología Celular y Biomedicina Facultad de Medicina y Ciencia. Universidad San Sebastián, Santiago, Chile, ⁹Centro de Investigación Clínica de Morelia SC, Morelia, México, ¹⁰Department of Internal Medicine, Division of Rheumatology, University of Puerto Rico, San Juan, Puerto Rico, ¹¹The University of Alabama at Birmingham, Birmingham, Estados Unidos.

Objectives: Classifying patients as having SLE is critical for clinical trials and observational studies; they are frequently used in clinical practice for early diagnosis. The SLICC 2012 criteria are more sensitive but less specific than the 1982/1997 ACR criteria. The 2018 EULAR/ACR criteria require a positive ANA as the entry point; clinical manifestations are clustered into weighted domains to maximize the accurate SLE classification, particularly of early disease.

To identify the items of the clinical and immunological domains of the EULAR/ACR SLE criteria that differ in the time to criteria fulfillment when compared to the SLICC criteria in two multiethnic cohorts.

Methods: Patients from two multiethnic, multicenter cohorts, one from the US and the other from Latin America (LA) were included. For these analyses, EULAR/ACR items were evaluated to determine which clinical manifestations and/or laboratory parameters could be of help to achieve an earlier classification of patients. Categorical variables were compared using Chi-square or modified Fisher exact tests, as appropriate. The statistical analyses were performed using SAS software version 9.4.

Results: Five-hundred forty-two patients out of 640 from the US cohort and 978 out of 1047 from the LA cohort were included. Only 35(6.5%) and 6(0.6%) of the patients achieved the 2018 EULAR/ACR criteria earlier in the US and LA cohorts, respectively. In turn, about 118(21.8%) and 280(28.6%) of the patients achieved them later, while the majority of the patients attained them at the same time. US cohort patients who accrued the 2018 EULAR/ACR earlier were more likely to be African American and Hispanic (from Puerto Rico) and less likely to be Caucasian or Hispanic from Texas. They also had more often mucocutaneous manifestations, arthritis, pleurisy and renal involvement. In contrast, LA cohort patients achieving the same criteria earlier were more likely to be Mestizo than African-Latin American. These patients also had more frequently alopecia, acute cutaneous lupus, pleural/pericardial effusion, leukopenia, positive antiphospholipid, anti-dsDNA antibodies and low C3 and C4.

Conclusions: We found that only a small proportion of patients met the 2018 EULAR/ACR criteria earlier than the SLICC criteria with no clear demographic, clinical or laboratory features associated to the earlier identification of lupus using these new criteria. We found no advantage of the 2018 EULAR/ACR criteria over the SLICC criteria for earlier disease identification in patients from these cohorts.

256

COMPARISON OF ACR 1982/1997 AND EULAR/ACR CLASSIFICATION CRITERIA FOR SYSTEMIC LUPUS ERYTHEMATOSUS IN TWO MULTIETHNIC COHORTS

Guillermo Pons-Estel¹, Manuel F. Ugarte-Gil², Guillermina Harvey³, Daniel Wojdyla³, Russell Griffin⁴, Verónica Saurit⁵, Enrique Soriano⁶, Eloisa Bonfa⁷, Loreto Massardo⁸, Mario H. Cardiel⁹, Rosana Quintana¹, Graciela S. Alarcón¹⁰, and Bernardo Pons-Estel¹. ¹Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Rosario, Argentina, Rosario, Argentina, ²Universidad Científica del Sur, Lima, Perú, ³Universidad Nacional de Rosario, Argentina., Rosario, Argentina, ⁴Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, Estados Unidos, ⁵Hospital Privado Universitario de Córdoba, Córdoba, Argentina, ⁶Servicio de Clínica Médica, Instituto Universitario, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, ⁷Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de São Paulo, São Paulo, Brazil, ⁸Centro de Biología Celular y Biomedicina Facultad de Medicina y Ciencia. Universidad San Sebastián, Santiago, Chile, ⁹Centro de Investigación Clínica de Morelia SC, Morelia, México, ¹⁰The University of Alabama at Birmingham, Birmingham, Estados Unidos.

Objectives: Identifying SLE patients is critical for clinical trials and observational studies. The SLICC 2012 criteria are more sensitive but less specific than the 1982/1997 ACR criteria. The 2018 EULAR/ACR criteria differ from the others as they require a positive ANA as the entry point; in addition, the clinical manifestations are clustered into weighted domains to maximize the likelihood of an accurate SLE classification

The objective of this study was to identify the distinct items of the EULAR/ACR SLE classification criteria that differ in the time to criteria fulfillment when compared to the 1982/1997 ACR criteria in two multiethnic lupus cohorts.

Methods: Patients from two multiethnic, multicenter cohorts, one from the US and the other from Latin America were included. For these analyses, the 2018 EULAR/ACR criteria items were evaluated to determine which clinical manifestations and/or laboratory parameters could be of help in achieving an earlier classification of patients. Categorical variables were compared using Chi-square or modified Fisher exact tests, as appropriate. Of note, not all manifestations were available in these cohort. The statistical analyses were performed using SAS software version 9.4.

Results: Five-hundred and fifty-eight patients out of 640 from the US cohort and 956 out of 1047 from the Latin America cohort were included. Only 41 (7.3%) and 71 (7.4%) of patients achieved the 2018 EULAR/ACR criteria earlier in the US and Latin American cohorts, respectively. In turn, about one third of the patients in both cohorts achieved them later. Patients who accrued the 2018 EULAR/ACR earlier were more likely to have high anti-dsDNA titers and less likely to have mucocutaneous and joint manifestations.

Conclusions: When both cohorts were taken into account, those patients who achieved the 2018 EULAR/ACR criteria earlier had a lower frequency of milder manifestations (like mucocutaneous and articular) and tended to have a higher frequency of anti-dsDNA antibodies, suggesting these criteria could be more useful in subsets of patients with more severe disease.

257

MANIFESTATIONS OF ANCA-ASSOCIATED CNS VASCULITIS

Daniela Grünholz Gambi¹, Eduardo Waisntein Gurovich¹, and Jonathan Sapaag Kaminski². ¹Hospital Militar De Santiago, Santiago, Chile, ²Clinica Davila, Chile.

Objectives: The associated ANCA vasculitis correspond to systemic vasculitis that classically affect the upper airway, lung and kidney, however they can affect any organ. The involment of de central nervous system is rare; in granulomatosis with polyangiitis is described inbetween 2-8% of the patients the clinical presentation can be very serious or lethal, so an early and accurate diagnosis reduces complications. The neurological manifestations most frecuently described are pachymeningits, vasculitis of cerebral arteries, hypophyfitis, opnic neuritis and sensorioneural hearing loss. Belox we describe seven cases that were presented between 2014 and 2018 in the reumathology service of highly complex hospital in Santiago, Chile

Methods: After obtaininig the informed consent and the appoval of the local scientific ethics committee, an analysis of the patients records was carried out; data were obtained on the clinical presentation and management.

Results: We managed to obtain the data of 7 patients, 3 men and 4 women, average age at diagnosis of 64 years (45-70), 6/7 patiens were PR3 positive and 1 MPO positive; the form of presentation was as follow: 2 casese of retroorbital mass, 2 cases of pachymeningitis, 2 casese of hypophysitis, 1 case of sensorimotor otic involvement. In 3/7 patients the first manifestation of the disease were CNS symptoms; in the other 4 patients the diagnosis of vasculitis had been made previously.

6/7 patients received tratment with rituximab as management of neurological manifestations with excellent clinical course, and 1 patient with periorbital mass had a good response to cyclophosphamide. Of the 7 patients, most received previous treatment with cyclophosphamide or methotrexate and the decision to start rituximab was due to lack of response to previous treatment.

Conclusions: The neurological manifestations of ANCA- associated CNS vasculitis are rare but can be fatal or cause many sequelae. To our knowledge there are only reports of cases described in the foreing literature, most cases reports are from Japan. As described in the literature, most patients were PR3+. ANCA- associated CNS vasculitis can ensue in patients already diagnosed or be the first clinical manifestation. Rituximab seems to be an excellent therapeutic tool in this group of patients.

267

HOSPITALIZATION OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS DURING A PERIOD OF 5 YEARS IN A UNIVERSITY HOSPITAL

Paulo Roberto Donadio¹, Maria Natália Marques dos Santos¹, Luiz Felipe Moraes Schwerz Bonadiman Blanco¹, Louise Ferreira Iunklaus¹, Pedro Henrique Iora¹, Beatriz Medeiros Gurgel¹, Vinicius Luís de Freitas Souza¹, and Leonardo Grande de Almeida¹. ¹Universidade Estadual De Maringá, Maringá, Brazil.

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin characterized by the formation of antibodies and deposition of immunocomplexes in various organs. In Brazil, there are 8.7 cases per 100,000 people per year, more frequently affecting African American and Hispanic women aged 20-40. We conducted this research with the objective of describing and analyzing the clinical characteristics and the course of the disease in patients with SLE hospitalized during a 5-year period in a tertiary referral hospital.

Methods: The hospitalizations were analyzed from January 2013 to December 2017. Data on age, gender, disease duration, medications used, reason for hospitalization, time and outcome of hospitalizations, hemodialysis, were collected directly from the medical records of these patients. The Excel and RStudio programs were used for data analysis: the first one was used to tabulate collected information, the second one was used for descriptive statistics and mean difference test.

Results: 228 medical records of patients being cared for at the Rheumatology outpatient clinic during the mentioned period were evaluated. There were 112 hospitalizations in61 patients (59 women and 2 men), approximately 26.7% of the patients being followed up, with an average of 5.82 days of hospitalization. The hospitalizations of patients with SLE occur more frequently in female patients, of fertile age, with an average disease duration of 7,92 years, and average of 5,82 days of hospitalization. The major reasons for hospitalization were a flare of the disease and the presence of infection, highlighting urinary and pulmonary tract infections as the most prevalent sites, and the use of corticosteroids associated with higher readmission rates, associated with systemic arterial hypertension.

Conclusions: As presented in this study, we conclude that hospitalizations of SLE patients occur more frequently in female patients of childbearing age, with an average disease duration of 7.92 years and an average of 5.82 days of hospitalization. The major reasons for hospitalization were disease reactivation (flares) and the presence of infection, highlighting urinary and pulmonary tract infections as the most prevalent sites; the use of corticosteroids was associated with high rehospitalization rates, especially in the presence of systemic arterial hypertension.

273

AMYLOIDOSIS IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND SECONDARY ANTIPHOSPHOLIPID SYNDROME: A RARE ASSOCIATION

Paulo Roberto Donadio¹, Paola da Costa Souza¹, César Orlando Peralta Bandeira¹, Ademar Lucas Junior, and Luciano H Scremim. ¹Universidade Estadual De Maringá, Maringá, Brazil.

Objectives: Report a case of a patient with systemic lupus erythematosus (SLE) and secondary Antiphospholipid syndrome (APS), who developed amyloidosis. Amyloidosis is described as a complication of chronic infections, and autoimmune rheumatic diseases, especially rheumatoid arthritis. Localized forms of amyloidosis in the oropharynx, larynx, and trachea are usually unrelated to other chronic diseases.

Methods: Female, 43 years old. Diagnosed with Lupus 9 years beforeand secondary APS with history of 3 pregnancies (1 cesarean delivery, and 2 abortions - 20th week and 8th week) and deep venous thrombosis. ANA 1/640 homogeneus; Anti-DNA: 1/160; Lupus anticoagulant: 2.08; Anticardiolipin IgM: 60.2 MPL/ml. One year before presentation, she developed a persistent sinusitis, with sensation of pressure in the left ear. At presentation her nasal sinus examination showed lesion in the rhinopharynx and auditory tube on the left. Otoscopy: slight pallor and bulging tympanic membrane. Endotracheal intubation for tympanostomy revealed partial obstruction of the trachea. Bronchoscopy: submucosal lesion in the posterior subglottic region causing partial light obstruction. Biopsy of the affected area was: suggestive of amyloidosis. Histochemistry and Congo Red staining confirmed the diagnosis. Magnetic resonance images: left and subglottic parapharyngeal lesions with marked luminal stenosis, with flow voids compatible with calcifications, characteristic of amyloid protein deposition. Warfarin was restarted, and hydroxychloroquine and colchicine added, with good response.

Results: The association of amyloidosis with chronic rheumatic diseases, mainly rheumatoid arthritis, has been described less frequently, due to the earlier treatment and control of these diseases, with prevalence estimated between 1 and 2%/million inhabitants. Mortality is mainly related to renal and cardiac forms. Localized involvement of the upper airways is rarely associated with systemic diseases, with Sjögren's Syndrome being described more frequently; there is no consensus for treatment of this presentation, but colchicine can be used successfully.

Conclusions: The case reported of localized and clinically stable amyloidosis, was treated with colchicine. As she is a patient with SLE and secondary APS, with a history of miscarriages and a venous thrombotic event, she is also receiving treatment with warfarin and hydroxychloroquine. Medline and LILACS sources searches for this association were negative; thus, the authors believe that this may be the first case of this unusual association in the medical literature.

285

REJA-VASCA: JAVERIAN REGISTRY OF PATIENTS WITH ANCA POSITIVE VASCULITIS AT SAN IGNACIO UNIVERSITY HOSPITAL (HUSI) 2005-2017

Daniel Fernández-Ávila¹, Juan Gutiérrez¹, Julián Rondón¹, and Catalina Villota¹. ¹Pontificia Universidad Javeriana - Hospital Universitario San Ignacio, Bogotá, Colombia.

Objectives: To describe the clinical characteristics of patients with ANCA positive vasculitis at the University Hospital San Ignacio between 2005-2017.

Methods: Descriptive cross-sectional study. Patient records were reviewed between January 2005 and December 2017. The records were obtained using search systems in patients in whom ANCAs were requested (DISEARCH, LABCORE), obtaining 2072 results. 106 patients met the criteria for classification of the American College of Rheumatology (ACR) for ANCA-associated vasculitis (AAV).

Results: 106 patients diagnosed with ANCA positive vasculitis. Average age 55 years (± 14.7). 48.4% were women. In-hospital presentation in 68.8%. The average number of hospital days of stay was 16.6 (± 12.22), 56 patients (52.8%) had granulomatosis with polyangiitis GPA, 45 patients (42.4%) had microscopic polyangiitis (MAP) and 5 patients had eosinophilic granulomatosis with polyangiitis EGP (4.8%). 37 patients (35%) presented with alveolar hemorrhage, 22 patients (20.7%) presented renal compromise with rapidly progressive glomerulonephritis. Central nervous system compromise was documented in 25 patients (24%). Regarding treatment, 97 patients (91.5%) received treatment with intravenous or oral corticosteroid, 66 patients (62.2%) received treatment with cyclophosphamide. Plasma exchange therapy was performed in 15 patients (14.1%). 44 patients (41.5%) required renal replacement therapy. The in-hospital mortality of this group of patients was 20.4%, with sepsis being the most frequent cause of death (55%).

Conclusions: In this study, the most frequent ANCA positive vasculitis was GPA. Multisystemic compromise was present in all patient groups, the most common being pulmonary and renal, mainly in patients with MPA, similar to that reported by Solans-Laqué et al in Spain. Within the demographic characteristics, the average age at the time of diagnosis was around 50 years, predominantly in women which is consonant with the data from the Mexican study by Hinojosa-Azaola et al. The most frequent cause of in-hospital mortality was sepsis. Clinical information of patients with AAV is presented in a reference hospital in Colombia.Data are concordant with the literature.

286

SYSTEMIC LUPUS ERYTHEMATOUS WITH INFLAMMATORY MYOSITIS

Nicole Bitencourt¹, Bonnie Bermas¹, E. Blair Solow¹. ¹UT Southwestern Medical Center, Dallas, United States.

Objectives: Inflammatory myositis occurs in about 3-8% of patients with systemic lupus erythematosus (SLE). In patients with SLE and inflammatory myopathy, myalgia and Raynaud’s phenomenon are common. Muscle biopsies are often consistent with dermatomyositis-like findings. The goal of this study was to identify common serologic, clinical, and pathologic features of patients with overlapping SLE and inflammatory myositis.

Methods: A medical records review was performed of patients seen at a single center safety net hospital who had an encounter diagnosis of SLE by ICD-10 code [M32.x, also included M36.x] and a history of muscle biopsy, EMG (electromyography), or elevated creatinine kinase or aldolase. Diagnosis of SLE was confirmed by one author (NB) using the 2015 American College of Rheumatology (ACR)/Systemic Lupus International Collaborating Clinics (SLICC) criteria. Patients with inflammatory myositis were defined by either muscle biopsy or with creatinine kinase (CK) elevation with muscle weakness with or without muscle magnetic resonance imaging (MRI) consistent with myositis. Data on patient demographics, clinical and laboratory features were extracted following approval by the Institutional Review Board (IRB). Chi-square was used to analyze serologic and clinical features and compare patients with scleroderma features to those without them.

Results: Ninety percent of patients identified as having SLE and inflammatory myositis were female and 60% were of African descent. Average age at SLE diagnosis was 34 years (range 14 – 57). A positive RNP (present in 75% of patients) was the most common serologic feature present. Among those in whom it was checked, about half of patients (18 of 37) had a myositis specific or myositis associated antibody.

Sixteen patients had a muscle biopsy available for review. Non-specific inflammatory changes were the most commonly observed muscle biopsy feature, followed by tubuloreticular inclusions by electron microscopy. Autoimmune necrotizing myopathy was described in four patients.

Just over half (27 of 52) of the patients identified with an inflammatory myositis and SLE also had features of systemic sclerosis clinically. Arthralgias and inflammatory arthritis were the most common clinical feature found, followed by Raynaud’s phenomenon. A surprisingly large percentage (33%) had thrombotic events.

Conclusions: Features of patients with inflammatory myositis and SLE are described. About half of the patients with SLE and myositis have clinical features of systemic sclerosis. Inflammatory myositis among patients with SLE appears to occur more commonly among patients of African descent. Myositis related, and myositis specific antibodies are common in patients with SLE and myositis. Muscle biopsy among patients with SLE and myositis has a wide range of findings, including pauci-immune necrotizing myopathy, dermatomyositis features, polymyositis features, and neurogenic atrophy. Thrombotic events are common among patients with SLE and inflammatory myositis.

296

DIAGNOSTIC VALUE OF PULMONARY ULTRASOUND IN THE ASSESSMENT OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS

Marwin Gutierrez¹, Annamaria Iagnocco², Chiara Bertolazzi¹, Fausto Salaffi³, Jaime Mendoza¹, Luis Rodriguez¹, Carlos Pineda¹, Denise Clavijo-Cornejo¹. ¹Division of Musculoskeletal and Rheumatic Disorders, Instituto Nacional De Rehabilitacion, Mexico City, México, ²University of Turin, Turin, Italy, ³Universita Politecnica delle Marche, Jesi, Italy.

Objectives: To investigate the validity of ultrasound (US) in detecting subclinical interstitial lung disease (ILD) in systemic sclerosis (SSc) and to determine its potential in disease progression.

Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and pulmonaryfunction tests (PFT) were performed. An expert rheumatologist blinded to the clinical data performed the pulmonary US. To determine the concurrent validity high-resolution CT (HRCT) scans were performed. After the baseline assessment, the patients were followed every 3 months for 12 months.

Results: A total of 54 of 133 patients (40.6%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and the RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6%, respectively. A good inter-observer reliability was observed (k = 0.72).

In the follow-up, a total of 30 patients (22.6%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US.

Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitor disease progression.

297

EVALUATION OF TWEAK AND MCP-1 AS URINARY BIOMARKERS FOR THE EVALUATION OF LUPUS NEPHRITIS ACTIVITY

Esther Casablanca Alarcón¹. ¹INMUNOMED S.R.L., Cochabamba, Bolivia.

Objectives: To associate the urinary levels of TWEAK, MCP-1 and serological markers with remission and reactivation in lupus nephritis

Methods: Eighty-five patients were included (22 controls and 63 cases), who signed their consent prior to study participation. The control group corresponded to patients without clinical and family history of autoimmune disease. The case group met at least 4 criteria of the American College of Rheumatology for lupus diagnostic. This group was subdivided into 4 subgroups according to the activity of the disease. The levels of anti-ds-DNA, C3 and C4 complement levels, and clinic story of patients evaluated the activity of the disease; qRT-PCR was employed to measure the urinary levels of expression of the cytokine TWEAK and the chemokine MCP-1. The levels of these molecules were associated with the serum values of serological markers commonly used in clinical follow-up.

Results: The mRNA urinary expression of TWEAK and MCP-1 was significantly increased in patients with active LN (p <0.05). TWEAK expression correlated positively with serum levels of anti-dsDNA, anti-nucleosome and β2-microglobulin (r = 0.414 p <0.001, r = 0.405 p <0.001, r = 0.427 p <0.001). The level of expression of MCP-1 was positively associated with TWEAK expression levels (r = 0.299 p = 0.031), serum levels of anti-ds-DNA and anti-nucleosome antibodies (r = 0.390 p <0.05); r = 0.376 p <0.05).

TWEAK and MCP-1 mRNA expression were compared in the different study groups. There were significant differences in the expression levels of TWEAK in lupus patients with active disease versus those who were in remission with 58.3% (group I) and 100% (group II); the average of expression for both groups being 6 times higher than in patients with SLE in remission.

Conclusions: The present study demonstrates that MCP-1 and TWEAK can be considered as useful biomarkers to measure LN activity. There were differences between the expression levels of TWEAK and MCP-1 in patients with SLE and active LN with respect to those who were in remission or who belonged to the control group. Therefore, TWEAK cytokine and MCP-1 chemokine correlate positively with those patients who have active disease confirmed with high levels of anti-dsDNA antibodies, which suggests worsening of the disease. The measurement of mRNA expression levels of MCP-1 and TWEAK are non-invasive methods for the evaluation of LN.

302

THE SAFETY PROFILE OF THE DIALYZABLE LEUKOCYTE EXTRACT TRANSFERON USED AS AN ADJUVANT IN PATIENTS WITH AUTOIMMUNE DISEASE AND ITS EFFECT IN RHEUMATOID ARTHRITIS

Toni Homberg Von Thaden¹, Erika Vera Pérez¹, Edgar Cervantes Trujano¹, Andaluz Consuelo Garza¹, Julio Ayala Balboa¹, Maricela Martínez Corona¹, Martin Hernández Quiroz¹, Sonia Mayra Pérez Tapia¹, María del Carmen Jiménez Martínez². ¹Instituto Politécnico Nacional, Ciudad De México, México, ²Universidad Nacional Autónoma de México, Ciudad De México, México.

Objectives: Clinical research requires thorough evaluation of adverse events in patients exposed to new pharmaceutical agents. The Dialyzable Leukocyte Extract Transferon (DLE-T) is a complex drug, being itsmain component a mixture of human leukocyte-derived peptides less tha 10kDa in size which induces IFN gamma and it is being investigated as an immunoregulator.

The purpose of this study was to determine the safety profile of DLE-T in patients with autoimmune disease who have been treated with DLE-T as an adjuvant and provide evidence for its efficacy in rheumatoid arthritis.

Methods: This was a longitudinal study which evaluated the occurrence of serious and non-serious adverse events during DLE-T use in patients with autoimmune disease. Patients received oral DLE-T in varying doses (depending on disease activity) as an adjuvant to standard treatment in an ongoing safety and efficacy trial (IC 12-003). Efficacy was evaluated in a subgroup of patients with rheumatoid arthritis by measuring the changes in the Spanish Stanford Health Assessment Questionnaire (HAQ) 20-item Disability Index Scale scores. The HAQ addresses 8 sections: dressing, arising, eating, walking, higiene, reach, grip and activities, and scoring within each section is from 0 (without any difficulty) to 3 (unable to do). In this subgroup, DLE-T was added to conventional treatment in a weekly oral dose of 2mg/5mL for 4-6 months. HAQ scores were obtained before and 4-6 months after DLE was added.

Results: Safety: We evaluated 2179 patients with autoimmune disease who used DLE-T as an adjuvant. 176(8%) patients presented non-serious adverse events during DLE-T use. No patients presented serious adverse events. The most frequent adverse event was fatigue in 43(1.9%) patients, followed by headache in 39(1.8%) and joint pain in 21(1%). Adverse events were more frequent in pediatric patients (13.3% of all children exposed) as compared to adults (7.9%). Efficacy: 24 patients (23 female) with rheumatoid arthritis, ages 54±11 years added DLE-T to conventional treatment. Conventional treatment included methotrexate (67%), azulfidine (42%), oral glucocorticoid (38%), hydroxychloroquine (38%), leflunomide (8%) in various combinations plus non-steroidal antiinflammatory drugs (NSAID) (88%). 2 patients (17%) used no disease modifying agents and only NSAID due to liver damage. Baseline disability scores were 1.69±0.78. After 4-6 months of DLE-T use, mean disability scores were 1.29±0.75, p=0.001. 18(72%) patients showed improvement in disability scores, 11(46%) decreased the disability level.

Conclusions: DLE-T is safe to use as an adjuvant in autoimmune disease, no single adverse event was frequent (≥2% of the exposed population). It may improve symptoms in rheumatoid arthritis, but further controlled studies are needed to confirm our results.

306

CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Juan Camilo Díaz-Coronado^1,2, Sebastián Herrera-Uribe¹, Deicy Hernandez¹, Laura Betancur-Vásquez², Jorge Lacouture-Fierro², Daniel Gonzalez-Hurtado², Juanita Gonzalez- Arango², Laura Uribe-Arango², Maria Fernanda Saavedra-Chacón², Santiago Monsalve-Yepes², Sebastián Guerra-Zarama², José David Serna-Giraldo², Juan David López-López², Julián Barbosa-Arana², Maria Camila Soto-Osorio², and Ricardo A. Pineda-Tamayo¹. ¹Grupo de información clínica, Artmedica, Medellín, Colombia, ²Departamento de medicina interna, Universidad CES, Colombia.

Objectives: Systemic lupus erythematosus (SLE) is a chronic, recurring and multisystemic autoimmune disease. SLE patients have 5-6 times greater cardiovascular risk than the general population due to a higher prevalence of traditional risk factors, such as high blood pressure, smoking, obesity, and inflammatory phenomena secondary to the disease and corticosteroid use, with an accelerated atherosclerosis. Our objective was to describe the associated characteristics with cardiovascular risk in a cohort of SLE patients and to compare these with a subgroup that has had cardiovascular events such as acute myocardial infarction (AMI) and non-fatal stroke.

Methods: This is a cross-sectional study including 1175 patient registers, that fulfilled the ACR 1997 or SLCC 2012 classification criteria and were attended in rheumatologic institutions between 2015 to 2017, in the Colombian cities of Medellín, Bogotá, Pereira, Armenia, Manizales, and Montería. We describe de sociodemographic features and clinical characteristics including exposure risk factors. Consequently, we compared these aspects between patients who presented cardiovascular events with those who did not present them.

Results: 91% were women and the average age was 43.9. The prevalence of hypertension was 27%, active cigarette smoking 61% and 36% of the population were obese and overweight. The prevalence of cardiovascular events was 5.2%, AMI contributed with 3% and non-fatal stroke with 2.2%. When comparing patients with and without cardiovascular events it was found that the first group was7 years older on average and had a longer disease duration (p<0,001). The prevalence of hypertension was higher in the group with cardiovascular events and was 57% (p<0,001). This group also showed higher damage index scores, being SDI >=1 (10% vs 5,4%). The results of this study are similar to those reported in other cohorts, highlighting that hypertension and age as traditional cardiovascular risk factors. The natural course of the disease is that major risk factor may contribute to cardiovascular disease with persisting inflammation and endothelial injury

Conclusions: Cardiovascular risk factors are more frequent in patients with SLE than in general population. The course of the disease is a frequent risk factor to highlight in patients with SLE and established cardiovascular events. This fact emphasizes the importance of effective and timely intervention of the described risk factors.

310

MACULOPATHY INDUCED BY ANTIMALARIALS IN A COHORT OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS FROM COLOMBIA

Sebastián Herrera¹, Juan Camilo Diaz-Coronado^1,3, Deicy Hernandez¹, Yecenia Durango¹, Marcela Posada², Jorge Mora², Mariana Montoya², Mateo Calle Estrada², Cristina Posada², Juanita Montaño², Mateo Calle Estrada², Maria Camila Soto², and Ricardo Pineda-Tamayo¹. ¹Grupo de información clínica, Artmédica, Medellín, Colombia, ²Hospital General de Medellín “Luz Castro de Gutiérrez”, Colombia, ³Universidad CES, Colombia.

Objectives: Antimalarials (AMs) are an essential part of the treatment of systemic lupus erythematosus (SLE). Although they are safe, they have adverse effects that sometimes force patients to stop them increasing the risk of relapse. The current guidelines for the screening of maculopathy by antimalarials (MAM) do not have a big participation of rheumatology groups, generating controversy about the impact of some of their recommendations

Methods: We obtained data from a cohort of 1209 patients with SLE, followed between the years 2015 to 2018. A comparative analysis of patients with MAM outcome was carried out with different exposure groups, through Chi square and U de Mann-Whitney, getting raw OR association. A model was constructed taking into account crude associations with p <0.05, those that met the criteria of Hosmer Lemeshow and those that due to biological plausibility and literature review were important such as: use of chloroquine (CQ), age, dose in mg/kg of AMs, SDI damage index >0 and total cumulative AM dose. Logistic regression was performed to obtain adjusted OR.

Results: We analyzed 1006 patients, 72.2% used CQ and 27.7% used HCQ, were detected 7% cases of MAM. 6.6% due to CQ and 0.5% to HCQ.

In unadjusted analysis the use of HCQ showed lower probability of developing MAM (OR 0.21 CI95% 0.09-0.49). The cumulative dose of AMs ≥5.1mg/kg/day increased the risk of maculopathy (OR 5.6 CI95%1,04 – 32). The low weight, renal failure and age greater than 60 years, did not show significant differences.

In the subgroup’s analysis, patients who used CQ and had a BMI <18.5, GFR <30ml/min and liver disease had a greater proportion of maculopathy than those who used HCQ (P<0.02).

The dose of CQ <3mg/kg/day has a lower proportion of maculopathy compared to HCQ, and as a cumulative dose <400gr OR 0.89 (CI95% 0.81-0.97).

In our results, the dose of AMs associated with MAM is higher than the upper limit proposed in current screening guidelines.

Conclusions: We suggest an overestimation of the association with retinal toxicity due to CQ. In some subgroups of risk, we found association with maculopathy (BMI, dose, use of CQ, liver disease, renal dysfunction) are similar to those usually described in the literature as predisposing to ocular toxicity.

316

CRYPTOCOCCUS MENINGITIS BY CRYPTOCOCCUS GATTII IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Paulo Roberto Donadio¹, Felipe Merchan Ferraz Grizzo¹, Lorena Bossoni Miosso Marchiotti¹, Sueny de Paula Monarin¹, Gabriel Bortoli Ramos¹, Milene Cripa Pizatto de Araújo¹, Rodolfo Grillo Menegon¹, Vitor Corsaletti Abreu¹, and Pedro Henrique G de Andrade¹. ¹Universidade Estadual De Maringá, Maringá, Brazil.

Objectives: Cryptococcosis is a fungal infection of a systemic and opportunistic nature that occurs through the inhalation of Cryptococcus spp, mainly Cryptococcus neoformans, that affects immunocompromised individuals, especially those with acquired immunodeficiency syndrome, and Cryptococcus gattii, that affects mainly immunocompetent individuals. In systemic lupus erythematosus (SLE) treated with immunosuppressants, cases of this fungal infection, usually by Cryptococcus neoformans, with a much lower frequency and more favorable evolution, without a significant increase in mortality, nor severe sequelae are also reported. The authors describe the case of a patient with SLE who presented fungal infection of the central nervous system by Cryptococcus gattii.

Methods: Female, 26 years old, with SLE and nephritis class IV, on treatment with monthly pulse of cyclophosphamide, third cycle on 03/04/2012, and prednisone 60 mg/day, presented a holocranial headache one week before presentation, nausea and vomiting; and 2 days before, fever (38°C - 40°C). Physical examination: no neck stiffness or focal deficit. Computed tomography of the skull showed an increase of basal cisterns, brain grooves and lateral fissures. No further changes. CSF showed 3 erythrocytes/mm³, 1277 leukocytes/mm³ (87% mononuclear), 182 mg/dl protein, glucose <20 mg/dl, lactate 47 mg/dl. India ink staining showed the presence of Cryptococcus sp. Cryptococcal antigen 1: 4096, VDRL and BAAR negatives. Serology for HIV negative. Culture for fungi showed growth of Cyptococcus gattii. Treated with Amphotericin for 21 days and Fluconazole for 48 days, evolved without sequelae

Results: With the evolution of therapy for SLE, the survival of patients with SLE has increased significantly; there has been also a reduction in mortality rates due to complications of the disease. In contrast, death rates from infections have increased; as to to CNS involvement, fungal infections have been reported as the most important ones, especially those caused by Cryptococcus spp. Cryptococcus neoformans has the characteristic of infecting immunosuppressed patients, while Cryptococcus gattii, which predominates in tropical countries, is more commonly associated with infections in immunocompetent patients.

Conclusions: The case described here can be considered a rarity, since there was culture evidence of Cryptococcus gattii, which, as far as we were able to verify, there is no evidence in the literature of Cryptococcus meningitis for this serotype in patients with SLE. The treatment instituted completely controlled the clinical manifestations leaving no neurological sequelae.

322

PERFORMANCE OF SLEDAI-2K RESPONDER INDEX-50 IN A RANDOMIZED PLACEBO-CONTROLLED TRIAL WITH USTEKINUMAB (UST) IN SYSTEMIC LUPUS ERYTHEMATOSUS

Zahi Touma¹, Dafna Gladman¹, Kaiyin Fei², Irene Gregan², Federico Zazzetti³, Robert Gordon², Kim Hung Lo², Shawn Rose², and Murray Urowitz¹. ¹Krembil Research Institute, Toronto, Canada, ²Janssen Research & Development, LLC, Spring House, United States, ³Janssen-Cilag, Buenos Aires, Argentina.

Objectives: While traditional Systemic Lupus Erythematosus (SLE) Disease Activity Index 2000 (SLEDAI-2K) scoring assesses complete SLE response for individual disease manifestations, the SLEDAI-2K Responder Index-50 (S2K RI-50) evaluates responses using partial improvement (≥50%) in each of the 9 organ-systems of SLEDAI-2K and generates a total score. We aimed to evaluate the performance of S2K RI-50 at 24 weeks in a randomized, placebo (PBO) controlled trial of UST in patients with moderate-to-severe SLE disease activity to ascertain a minimal threshold of partial improvement.

Methods: The UST phase 2, PBO-controlled study enrolled adults with active disease (SLEDAI score ≥6 with ≥1 BILAG A &/or ≥2 BILAG B scores) despite standard-of-care therapy. Patients (n=102) were randomized (3:2) to receive UST IV ~6 mg/kg or PBO at week (wk) 0, followed by SC injections of UST 90mg q8w or PBO beginning at wk8, both added to standard of care. We calculated S2K RI-50 response in patients receiving UST (n=62) vs PBO (n=40) at wk24 using increasing S2K RI-50 reductions of 1, 2, 3, 4, 5, or 6 points from baseline to determine ≥50% improvement. In order to determine a minimal cut-off to discriminate a treatment effect reflecting partial improvement, nominal α level was set at 0.05 for this post hoc analysis.

Results: The performance of S2K RI-50 in detecting the treatment difference between UST and PBO was examined. A 2-point reduction in S2K RI-50 was the lowest threshold to demonstrate a p-value <0.05 (response rates were UST (93.5%); PBO (79.3%); treatment difference 14.2%, p=0.03). As an example, this could reflect partial improvement in one of the following: renal, arthritis, or myositis, or partial improvement in two of the following disease manifestations: rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement or increased anti-dsDNA.

Conclusions: S2K RI-50 captures partial improvement of ≥50% in SLE disease activity in the most common disease manifestations in SLE. S2K RI-50 could be used as an outcome in clinical trials as a clinically meaningful measure of partial improvement.

3. RHEUMATOID ARTHRITIS

26

LIVER ENZYME ABNORMALITIES AFTER TOFACITINIB TREATMENT IN PATIENTS WITH HEPATIC STEATOSIS FROM THE RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS, AND PSORIASIS CLINICAL PROGRAMS

Enrique R. Soriano¹, Hugo Javier Madariaga², Oswaldo Castañeda³, Gustavo Citera⁴, Emilce E. Schneeberger⁴, Mario H. Cardiel⁵, Thijs Hendrikx⁶, Daniela Graham⁷, Harry Shi⁶, and Dario Ponce de Leon⁸. ¹Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, ²Clínica del Sur, Arequipa, Perú, ³Clínica Angloamericana, Lima, Perú, ⁴Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ⁵Centro de Investigación Clínica de Morelia, Morelia, Mexico, ⁶Pfizer Inc, Collegeville, USA, ⁷Pfizer Inc, Groton, USA, ⁸Pfizer Inc, Lima, Perú.

Objectives: Non-alcoholic fatty liver disease, characterized by hepatic steatosis (HS), is a common form of chronic liver disease in many countries. Limited data are available on liver enzyme elevation in patients with HS receiving medications for inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO). Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA and PsA and has also been studied in PsO. The objective of this study was to describe baseline characteristics and liver enzyme abnormalities in patients from the tofacitinib RA, PsA, and PsO clinical programs with/without HS at baseline.

Methods: Patients randomized to the tofacitinib (5 or 10 mg twice daily; doses pooled) and placebo arms of 25 studies in the RA, PsA, and PsO clinical programs were included in this pooled post-hoc analysis. Most studies allowed or mandated concomitant treatment with disease-modifying antirheumatic drugs. HS was determined by the Investigator and captured per the Medical Dictionary for Regulatory Activities term at baseline. Baseline characteristics, incidence of elevated total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >1x and >3x the upper limit of normal (ULN) up to Month (M)3 and change from baseline in C-reactive protein (CRP) at M3 – all by HS at baseline – are reported.

Results: A total of 10,212 patients were included in the analysis. The prevalence of HS was 1.6% across indications (RA: 87/6,729 [1.3%]; PsA: 27/710 [3.8%]; PsO: 45/2,773 [1.6%]). Baseline characteristics were generally similar in patients with or without HS. However, baseline obesity, diabetes, triglycerides, and liver enzymes were numerically higher, and CRP was numerically lower, in patients with HS than in those without HS. In both tofacitinib- and placebo-treated patients, incidence of elevated total bilirubin, AST and ALT >1x ULN up to M3 was higher in patients with HS than in those without, across indications. Incidence of elevated total bilirubin, AST and ALT >3x ULN up to M3 was low across indications, irrespective of HS. Among tofacitinib-treated patients, CRP was reduced at M3 in patients with or without HS, but to a lesser extent in those with HS, across indications. Among placebo-treated patients, changes in CRP were small, irrespective of HS.

Conclusions: In this exploratory analysis, prevalence of HS at baseline was 1.6% across the tofacitinib RA, PsA, and PsO programs. After up to 3 months of tofacitinib treatment, incidence of mildly elevated liver enzymes was higher in patients with HS than in those without HS. Incidence of severely elevated liver enzymes was low overall, and similar in patients with or without HS. Further studies are needed to evaluate the effects of tofacitinib on CRP and liver enzymes – and the potential impact on clinical response – in patients with RA, PsA, or PsO who have comorbid HS.

30

EFFECT OF TOFACITINIB ON THE QUALITATIVE PROFILE OF HDL MOLECULES IN PATIENTS WITH RHEUMATOID ARTHRITIS

Florencia Pierini¹, Eliana Botta², Fernando Brites², Laura Boero², Maximiliano Martin², Tomas Meroño², Maria Soledad Saez², Walter Teztlaff², Fernando Sommerfleck³, Gustavo Citera³, Ignacio Gandino¹, Javier Rosa¹, Patricia Sorroche¹, and Enrique R. Soriano¹. ¹Hospital Italiano De Buenos Aires, Caba, Argentina, ²Universidad de Buenos Aires, CABA, Argentina, ³Instituto de Rehabilitación Psicofísica, CABA, Argentina.

Objectives: The objective of this study was to compare the functional markers of HDL at baseline and 3 months after starting Tofacitinib in patients with RA.

Methods: Patients with RA (according to ACR / EULAR 2010 criteria) with de novo indication of tofacitinib were included as of January 2016. Patients with a personal history of cardiovascular disease, impaired renal, hepatic or thyroid function were excluded. DAS 28, lipid profile, and ultrasensitive C reactive protein were analyzed by standardized methods at baseline and 3 months after starting tofacitinib. PON1 activity was evaluated by two substrates, paraoxon (PON activity) and phenylacetate (ARE activity). Differences in the quantitative variables were analyzed with paired Wilcoxon test and qualitative variables with McNemar test. Spearman test was used for correlations.

Results: Rheumatoid factor was positive in 70.6% (CI 52.4-83.9) and anti-CCP was positive in 82.3% (CI 64.8-92.2). 18 patients (52.95%), had received biologics previously. Mean baseline DAS28 was 5.1 (SD 1.1). At three months, DAS28 decreased significantly (-24%, p <0.001). As expected, levels of TC, LDL-c, HDLc and Coleshterol-non-HDL (C-non-HDL) increased significantly after 3 months of treatment (TC: + 8%, p = 0.046, LDL-c: 8%, p = 0.046; HDL-c: + 8%, p = 0.027 and C-non-HDL: + 13%, p = 0.031). No changes were observed in PON activity or ARE activity associated with tofacitinib use (p> 0.05) in the total group. Patients without previous biologics had a significant increase in the activity of ARE and PON, while there were no changes in those who had failed a previous biologic No significant changes were observed in the CETP in any of the groups.

Conclusions: Despite an increase in lipoprotein levels, treatment with tofacitinib improved the antioxidant activity of HDL (paroxonase activity) in patients who had not received previous biologic. This could provide additional protection to the accelerated atherosclerotic process in those patients.

38

DEPRESSION IS A MAJOR DRIVER OF FUNCTIONAL CAPACITY IN PATIENTS WITH RHEUMATOID ARTHRITIS REGARDLESS OF DISEASE ACTIVITY

Carolina Ayelen Isnardi¹, Dafne Capelusnik¹, Emilce Edith Schneeberger¹, Marcela Bazzarelli², Laura Barloco², Eliana Soledad Blanco³, Cristian Alejano Benitez³, Federico Lujan Benavidez³, Santiago Scarafia⁴, María Alicia Lazaro⁴, Rodolfo Pérez Alamino⁵, Francisco Colombres⁵, Paula Kohan⁶, Julia Sosa⁶, Luciana Gonzalez Lucero⁷, Ana Lucía Barbaglia⁷, Hernan Maldonado Ficco⁸, and Gustavo Citera¹. ¹Instituto De Rehabilitación Psicofísica, Caba, Argentina, ²Hospital Interzonal General de Agudos Petrona V. de Cordero, Tigre, Argentina, ³Hospital General de Agudos Dr. Cosme Argerich, CABA, Argentina, ⁴Instituto de Asistencia Reumatológica Integral, San Isidro, Argentina, ⁵Hospital de Clínicas Nicolás Avellaneda, San Miguel de Tucumán, Argentina, ⁶Hospital General de Agudos Dr. Enrique Tornú, CABA, Argentina, ⁷Hospital Ángel C. Padilla, San Miguel de Tucumán, Argentina, ⁸Hospital San Antonio de Padua, Rio Cuarto, Argentina.

Objectives: Depression is one of the most frequent comorbidities in Rheumatoid Arthritis (RA) patients. Its presence is associated with higher healthcare costs, mortality rate and reduced odds of achieving a good treatment response. The aim of this study was to determine the prevalence of depression in Argentinian patients with RA and to establish its relationship with different sociodemographic and clinical factors.

Methods: Consecutive patients ≥18 years of age, with a diagnosis of RA according to ACR-EULAR 2010 criteria were included. Sociodemographic data (sex, age, work and marital status, physical activity), comorbidities, RA characteristics (disease duration, RF and anti-CCP, presence of erosions), disease activity (joint count (28), composite indexes, pain, patient’s and physician´s global assessment-VAS-, morning stiffness), CRP, ESR and current treatment were registered. Questionnaires were administered to assess quality of life by EQ-5D-3L and QOL-RA, functional capacity by HAQ-A and depression by PHQ-9. Major depression was defined as a PHQ-9 score ≥10. PHQ-9 scores of 5-9, 10-14, 15-19, ≥20 represented mild, moderate, moderate/severe and severe depression, respectively. Patients with difficulties in answering the questionnaires (illiterate, blind) and with decompensated comorbidities were excluded. Statistical analysis: Student´s T, ANOVA and Chi² tests. Multiple logistic regression.

Results: 258 patients were included. Median (m) disease duration of 9 years (IQR 3.6-16.7). DAS28-ESR was m 3.5 (IQR 2.5-4.5). Median PHQ-9 score was 6 (IQR 2-12.3). The prevalence of major depression was 33.8%. 66 (25.6%), 42 (16.3%), 27 (10.5%) and 18 (7%) patients presented mild, moderate, moderate/severe and severe depression, respectively. Patients with major depression had worst functional capacity (HAQ mean 1.56 ± 0.78 vs 0.69 ±0.65, p=0.0001), poorer quality of life (QOL-RA mean 5.38 ± 1.78 vs 7.31 ±1.61, p=0.0001), more pain (VAS mean 56.15 ± 27.48 mm vs 33.42 ± 25.72 mm, p=0.0001) and higher disease activity (DAS28-ESR mean 4.33 ±1.39 vs 3.3 ± 1.28, p=0.0001). Unemployment, presence of comorbidities, and less physical activity were more frequent in this group. In the multivariate analysis, worse functional capacity and quality of life were independently associated with the presence of major depression, independently of disease activity.

Conclusions: The prevalence of major depression measured by PHQ-9 score in this Argentinian cohort of rheumatoid arthritis patients was 33.8%. Depression had a significant impact on functional capacity and quality of life, regardless of disease activity.

49

VITAMIN D LEVELS IN RHEUMATOID ARTHRITIS AND THEIR RELATIONSHIP WITH THE ACTIVITY OF THE DISEASE IN SANTO DOMINGO, DOMINICAN REPUBLIC

I. Mercedes-Núñez¹, E. Tejada-Reyes¹, M. Marte-Robles¹, R. Jimenez-Candelaria¹, V. Rosario¹, T. Valdez-Lorie¹, and R. Muñoz-Louis¹, and R. Alba-Fériz¹. ¹Hospital Docente Padre Billini, Dominican Republic.

Objectives: To estimate the frequency of low serum vitamin D level (25(OH)D) in patients with rheumatoid arthritis (RA), and to analyze the association between 25(OH)D and disease activity.

Methods: A cross-sectional study. Data were collected from the rheumatology service of Hospital Docente Padre Billini, which is a national reference hospital. We included all patients older than 18 years diagnosed with RA according to the ACR / EULAR 2010 criteria, during the months of July-December 2017. Patients with low doses of 25(OH)D before the study period were excluded. 25(OH)D levels were classified as deficient <10 ng / mL, Insufficient 10-30 ng / mL, sufficient 30-100 ng / mL. Disease activity was measured using the disease activity score index (DAS28). Were analyzed using the statistical software SPSS V23.

Results: A total of 867 patients, 136 patients met inclusion criteria. The mean age was 58.4 years, 94.9 (127) were women, mean disease duration 8.6 years, the 25(OH)D levels were: 1.5% (2) deficient, 68.4% (93) insufficient, 30.1 % (42) sufficient. In relation to the activity levels, 51.4% (48) of the patients with low levels of 25 (OH) D had moderate-high activity disease. Sufficient levels of vitamin D had 50.4% (22) moderate-high activity.

Conclusions: There was high frequency of 25(OH)D deficiency (69.9%) in our cohort, but there was not a significant relationship between these levels and the activity of the disease in RA. We must measure the levels of vitamin D in the general population to compare with our RA cohort. Despite being a Caribbean island, we found a high frequency of low levels of vitamin D.

62

COST-PER-RESPONSE ANALYSIS OF SUBCUTANEOUS ABATACEPT VERSUS ADALIMUMAB FOR THE TREATMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS – BRAZILIAN PRIVATE HEALTHCARE SYSTEM PERSPECTIVE

Nathalie Alves¹, Paola Marinheiro¹, and Graziela Bernardino¹. ¹Bristol-Myers Squibb, Sao Paulo, Brazil.

Objectives: The Brazilian Society of Rheumatology recommends the use of various biological medications for the treatment of Rheumatoid Arthritis (RA), including abatacept (ABA) and adalimumab (ADA). As the number of treatment options increases for patients with RA, understanding treatment efficacy and how it may improve resource allocation are key elements of decision-making. This study aims to compare the cost-per-response for subcutaneous (SC) ABA and ADA for each clinical outcome available in the 2-year follow-up of the AMPLE study (ACR20, ACR50, ACR70, ACR90 and remission [DAS28 < 2.6]).

Methods: AMPLE was a non-inferiority study that compared the efficacy of subcutaneous (SC) ABA vs. ADA in adults with moderate to severe RA, diagnosed ≤ 5 years and after treatment failure with methotrexate monotherapy. Prices approved by Brazilian Regulation Chamber of Drug Market (CMED)* were considered for costs. The exchange rate used was 1USD = 3,79 BRL, average rate for November 2018. The costs for each therapy were calculated for 1 and 2 years of treatment (52 and 104 weeks, respectively). The cost-per-response was calculated for the following outcomes: ACR20, ACR50, ACR70, ACR90 and remission [DAS28 <2.6].

*The prices considered were the official listed prices approved for the Sao Paulo region, published on 11/19/2018 by CMED.

Results: In both periods, the cost-per-response ratio for all evaluated outcomes favors treatment with ABA SC compared to ADA. For one year of treatment, the cost-per-response in USD were: ACR20: 29,453.37 vs 43,170.50; ACR50: 41,311.22 vs 59,500.20; ACR70: 65,362.27 vs 104,466.00; ACR90: 183,517.15 vs 427,657.69; DAS28: 44,078.02 vs 65,322.42. For two years of treatment, the costs-per-response in USD were: ACR20: 63,938.97 vs 89,395.14; ACR50: 85,395.00 vs 115,292.87; ACR70: 122,738.16 vs 183,366.82; ACR90: 263,252.19 vs 655,200.95; DAS28: 75,437.88 vs 100,800.14.

Conclusions: The analysis, which was based on the clinical outcomes observed in the AMPLE study, showed that the costs-per-response for ABA SC were lower when compared to ADA in the two periods evaluated. The present study suggests that treatment with ABA SC can lead to a decrease in health care costs in the Brazilian private healthcare system compared to ADA, in first line biologic for MTX-inadequate responders, with similar results in terms of clinical efficacy.

68

THE LEVEL OF ANXIETY AND ITS CORRELATION WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS TREATED WITH B-DMARDS AND NB-DMARDS

Ewa Mojs¹, Michal Ziarko², and Wlodzimierz Samborski³. ¹Poznan University of Medical Sciences, Department of Clinical Psychology, Poznan, Poland, ²Adam Mickiewicz University, Institute of Psychology, Poznan, Poland, ³Poznan University of Medical Sciences, Department of Rheumatology and Rehabilitation, Poznan, Poland.

Objectives: Rheumatoid arthritis (RA) is a long-term disorder significantly impairing the somatic, emotional, and psychological functioning of its sufferers. Previous research has shown that affected individuals are characterized by an increased level of anxiety and depression. Currently, there are two main treatment schemes for RA; the first uses classic drugs modifying the activity of the disease, the second utilizes biologic agents modifying the activity of the disease. This begs the question whether sufferers differ in intensities of pain, anxiety, ad depression depending on the type of treatment, everyday functioning and what the determinants of these affective states in patients with RA.

Methods: The study comprised 150 patients affected by RA (including 70 receiving disease modifying biologic therapies). Research participants filled out a set of questionnaires measuring: levels of states of anxiety and depression, intensity of experienced pain, strategies of coping with pain, and ego resiliency as personality potence.

Results: The collected data was analyzed through intergroup comparisons, calculating simple correlation coefficients, developing and solving regression equations. The results imply that the choice of treatment differentiates the intensity of pain experienced by patients during the treatment and level of everyday functioning. Those receiving biologic agents reported lower levels of pain compared to those taking classic medication. It has also been noted that there are distinct configurations of conditions conducive to anxiety and depression in both groups. The occurrence of depression was much higher – appr 30% in comparison to healthy groups.

Conclusions: The observed constellation of dependencies between variables indicates that the choice of treatment scheme differentiates pain levels. This confirms the assumption that pain intensity, coping strategies, and ego resiliency depend on the severity of anxiety and depression.

86

ADHERENCE TO TREATMENT WITH INTRAVENOUS (IV) BIOLOGICAL AGENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Gisele Luna¹, Fernando Dal Pra¹, Emilce Schneeberger¹, and Macias Lysseth, Gustavo Citera¹. ¹Irep, Buenos Aires, Argentina.

Objectives: To evaluate the adherence to biological IV DMARDs (-b) in patients with RA in clinical practice and to determine the factors that could have an impact on the adherence.

Methods: An observational study was conducted involving patients ≥18 years of age, with a diagnosis of RA according to ACR / EULAR 2010 criteria, who received at least 3 infusions of the DMARD-b IV abatacept (ABA) or tocilizumab (TCZ), during the course of their illness. Medical records were reviewed to collect: sociodemographic data, clinical characteristics of the disease, comorbidities, disease activity (DAS28) and functional capacity (HAQ). Information was obtained on previous and concomitant treatments with b-DMARDs, including steroids and conventional DMARDs (-c), number of infusions of b-DMARD received, date of their initiation and discontinuation and causes of discontinuation. Adherence was calculated as the number of infusions received during the treatment period, considering a 28 days interval between infusions as optimal. Statistical analysis: descriptive statistics, Chi square test or Fisher's exact test, Student's T test and Mann Whitney test. Multiple logistic regression model to evaluate predictors of good adherence (≥80%).

Results: 67 patients included (94%women), median age of 55 years and a median disease duration 13.75years, 93.5% Rheumatoid Factor +, 85% had erosive disease. 82.1% had medical coverage and 60% corresponded to social work. Median distance to the infusion center was 15 km. Forty-two patients received ABA and 25 received TCZ. 72.4% received cs-DMARD concomitantly. The baseline DAS28 decreased from 5.46 to 3.8, p<0.001 at 3 months, and the baseline HAQ-A from 2 to 1, p<0.001. After a median follow-up time of 2.42 years, 38 patients (56.5%) discontinued definitively the IV b-DMARD. Causes of discontinuation were lack of efficacy (62.9%), AE (20%) and medication either not available or not covered (14.3%). Median survival was 4 years. Median number of infusions per year was 10.17(IQR 8.3-10.9), equivalent to an adherence of 78.2. Median infusions/year correlated negatively with distance to the infusion center (Rho:-0.27,p=0.003) and was significantly lower in patients without health coverage (8.5±2.5vs10.7±1.5,p<0.001). In multivariate analysis, having health coverage was the only variable associated with adherence ≥80% (OR:6.27,95%CI 1.1-37.9, p=0.04)

Conclusions: Adherence to treatment with IV b-DMARDwas acceptable, however our patients lose an average of 3 infusions per year. The only independent predictor associated with good adherence was having health coverage.

88

LOW INTERSTITIAL LUNG DISEASE EVENT RATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: POOLED POST HOC ANALYSIS OF DATA FROM THE TOFACITINIB CLINICAL DEVELOPMENT PROGRAM

Gustavo Citera¹, Eduardo Mysler², Hugo Madariaga³, Mario H Cardiel⁴, Oswaldo Castañeda⁵, Aryeh Fischer⁶, Pascal Richette⁷, Sandra Chartrand⁸, Jin Kyun Park⁹, Sander Strengholt¹⁰, Jose Luis Rivas¹¹, Amit Thorat¹², Tanya Girard¹³, Kenneth Kwok¹⁴, Lisy Wang¹⁵, and Dario Ponce de Leon¹⁶. ¹Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, ²Organización Médica de Investigación, Buenos Aires, Argentina, ³Clínica del Sur, Arequipa, Perú, ⁴Centro de Investigación Clínica de Morelia, Morelia, Mexico, ⁵Clínica Anglo Americana, Lima, Perú, ⁶Department of Medicine, University of Colorado Denver, Denver, USA, ⁷Department of Rheumatology, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France, ⁸Department of Medicine, Hôpital Maisonneuve-Rosemont affiliated to Université de Montréal, Montréal, Canada, ⁹Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, ¹⁰Pfizer Inc, Capelle aan den IJssel, Netherlands, ¹¹Pfizer SLU, Madrid, España, ¹²Pfizer Ltd, Mumbai, India, ¹³Pfizer Inc, Montréal, Canada, ¹⁴Pfizer Inc, New York, USA, ¹⁵Pfizer Inc, Groton, USA, ¹⁶Pfizer Inc, Lima, Perú.

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is a common extra-articular manifestation of RA.¹ We investigated the incidence of ILD in patients with RA treated with tofacitinib in a post hoc analysis of data pooled from the tofacitinib clinical development program.

Methods: Incidence rates (IR; patients with events per 100 patient-years [PY]) of ILD events in patients with active RA, receiving tofacitinib 5 or 10 mg twice daily, were calculated using data pooled from 2 Phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension (LTE) trials (ORAL Sequel LTE main study database locked at time of analysis: March 2017). No patients with pre-existing ILD were included. Potential ILD events were adjudicated by 3 independent pulmonologists as ‘probable’ (compatible adverse event [AE] with supportive clinical evidence) or ‘possible’ (compatible AE with no supportive clinical evidence). ILD IRs are described by patient age and region, and over time. In P2/3/3b/4 studies, ILD IRs were compared for tofacitinib vs placebo. A descriptive case-matched control (1:5 ratio of patients with vs without ILD events, matched by age and gender) analysis identified potential ILD risk factors.

Results: Of 7061 patients (23,394 PY exposure), 42 (0.6%) had an ILD event (median time to event 1144 days). The ILD IR was 0.18 with both tofacitinib doses. IRs were numerically higher in patients aged ≥65 vs <65 years and Asian vs non-Asian countries; 95% confidence intervals were wide/overlapping. IRs generally remained stable over time. 17/42 ILD events (40.5%) were serious; 35/42 (83.3%) were mild to moderate in severity. ILD IRs were numerically lower with tofacitinib vs placebo. A numerically higher proportion of patients in the ILD group (n=42) vs control group (n=210) were: Asian (31.0% vs 17.6%); smokers/ex-smokers (50.0% vs 39.5%); RF-positive (89.2% vs 71.0%); anti-CCP antibody positive (54.8% vs 46.7%); had received prior MTX (90.5% vs 79.5%), non-MTX csDMARDs (61.9% vs 55.2%), TNF inhibitors (26.2% vs 18.6%), and concomitant glucocorticoids (71.4% vs 52.9%); and had higher baseline mean ESR (57.0 vs 46.9 mm/hr) and CRP (25.4 vs 15.4 mg/L).

Conclusions: In this post hoc analysis of data from P1/2/3/3b/4/LTE studies, ILD events following tofacitinib treatment were low, and were associated with known risk factors.

Reference:

1. Curtis J et al. Arthritis Res Ther 2015; 17: 319.

92

MUSCLE INVOLVEMENT AND PREVALENCE OF SARCOPENIA IN PATIENTS WITH RHEUMATOID ARTHRITIS

María Lorena Brance^1,2, Bernardo A Pons-Estel³, Norberto Javier Quagliato⁴, Marisa Jorfen⁵, Guillermo Berbotto⁶, Noel Cortese⁵, Juan C Raggio⁶, Juan Soldano⁴, Mariano Palatnik⁷, Ignacio Chavero¹, Carolina Dieguez¹, Ariel Sánchez⁸, Luis del Rio⁹, Silvana Di Gregorio⁹, and Lucas R. Brun^2,10. ¹Reumatología y Enfermedades Óseas, Rosario, Argentina, ²Lab. Biología Ósea. Univ. Nacional de Rosario., Rosario, Argentina, ³Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Rosario, Argentina, ⁴Hospital Provincial, Rosario, Argentina, ⁵Red Municipal, Rosario, Argentina, ⁶Hospital Eva Perón, Baigorria, Argentina, ⁷Centro de Reumatología, Rosario, Argentina, ⁸Centro de Endocrinología., Rosario, Argentina, ⁹CETIR, Barcelona, España, ¹⁰Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetric polyarthritis that can lead to joint deformity and disability. In addition, bones and muscles are also affected. Local osteoporosis develops first and then, it can progress to generalized osteoporosis. Sarcopenia is characterized by a progressive and generalized loss of muscle mass and strength. Aim: To evaluate the muscle mass and the prevalence of sarcopenia in patients with RA.

Methods: Adult RA patients (n=105) of both sexes and 100 subjects as control group (CG) matched by age, sex and body mass index (BMI) were included. Exclusion criteria: pregnancy, intestinal malabsorption, chronic liver or kidney disease, cancer and drug that could affect bone mass except glucocorticoids. Whole-body composition was measured by dual-energy X-ray absorptiometry (DXA, Hologic Discovery Wi). Sarcopenia was defined as low muscle mass (appendicular skeletal muscle mass/height² and low muscle function: muscle strength and/or physical performance). Muscle strength was evaluated by hand-grip strength (Baseline Hand Dynamometer, USA) in the dominant hand. The physical performance was evaluated by sit to stand, timed up and go and 8-foot walking test. The distribution of the data was evaluated with the Shapiro-Wilk test and the differences between groups were analyzed using the Student's t test or the Mann-Whitney test, as appropriate. Data were expressed as mean±SD and p<0.05 was considered significant.

Results: No differences in age, sex (CG: 84/16 F/M, RA: 87/18 F/M) and BMI were found between groups. Lower percentage of lean mass was found in RA patients (CG: 59.5%, RA: 57.0%; p=0.0120). In addition, lower muscle strength and/or physical performance in RA were found (handgrip strength= CG: 26.4±8.3 kg, RA: 17.7±8.9 kg, p<0.0001; sit to stand test= CG: 12.8±5.9 s, RA: 16.5±5.9, p<0.0001; timed up and go test= CG: 7.5±2.0 s, RA: 10.3±3.5 s, p<0.0001; 8-foot walking test= CG: 1.07±0.27 m/s, RA: 0.79±0.23 m/s, p<0.0001). Therefore, higher prevalence of sarcopenia in RA group was found (CG: 8.1%; RA: 44.3%; RR: 2.1; p<0.0001). While in the CG there was no cases of severe sarcopenia, in the RA group 33% were found. Moreover, a higher percentage of total fat (GC: 37.3±7.2%, RA: 40.9±6.8%, p=0.0062) and visceral fat (GC: 566.2±305.8 g, RA: 692.7±350.0 g, p=0.0090) were found in patients with RA.

Conclusions: A higher prevalence of sarcopenia was found in RA patients with an increase in total and visceral fat. The activity of the disease, immobility and treatment with glucocorticoids would affect the muscle mass in patients with RA and this could also give joint involvement, progressive loss of bone mass, greater risk of falls and consequently increased risk of fracture.

93

BIOLOGIC THERAPIES AND BONE LOSS IN RHEUMATOID ARTHRITIS. 3D ANALYSIS BY DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA)

María Lorena Brance^1,2, Bernardo A. Pons-Estel³, Norberto Javier Quagliato⁴, Marisa Jorfen⁵, Guillermo Berbotto⁶, Noel Cortese⁵, Juan C. Raggio⁶, Juan Soldano⁴, Mariano Palatnik⁷, Ignacio Chavero¹, Carolina Dieguez¹, Luis del Rio⁹, Ariel Sánchez⁸, Silvana Di Gregorio⁹, and and Lucas R. Brun^2,10. ¹Reumatología y Enfermedades Óseas, Argentina, ²Lab. Biología Ósea. Univ. Nacional de Rosario., Rosario, Argentina, ³Centro Regional de Enfermedades Autoinmunes y Reumáticas (CREAR), Rosario, Argentina, ⁴Hospital Provincial, Rosario, ⁵Red Municipal, Rosario, Argentina, ⁶Hospital Eva Perón, Baigorria, Argentina, ⁷Centro de Reumatología, Rosario, Argentina, ⁸Centro de Endocrinología, Rosario, Argentina, ⁹CETIR, Barcelona, España, ¹⁰Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.

Objectives: Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory symmetric progressive polyarthritis with bone involvement. While several studies show favorable bone effects of biological drugs, there are no conclusions about fracture prevention. The 3D analysis of the proximal femur by dual-energy X-ray absorptiometry (DXA) allows the evaluation of cortical and trabecular bone separately and has shown to have a very good correlation with computed tomography. Aim: Evaluate changes in cortical and trabecular bone in patients with RA treated with different therapies.

Methods: Adults female and male RA patients (n=105), 30 receiving biologic therapies (RA+Biol) and 75 receiving non-biological DMARDs (RA+No-Biol) were included. As control group (CG), 100 subjects matched by age, sex and body mass index (BMI) were included. BMD (g/cm2) was measured with DXA (Hologic Discovery Wi) on bilateral femoral neck (FN) and total hip (TH). The 3D analysis was performed with 3D-Shaper software (v2.9, Galgo Medical, Spain). The following parameter were considered: integral volumetric BMD (integral vBMD - mg/cm3), cortical BMD (sDens - mg/cm2) and trabecular volumetric BMD (trabecular vBMD - mg/cm3). The distribution of the data was evaluated with the Shapiro-Wilk test and parametric or non-parametric tests were used as appropriate. Data were expressed as mean±SD and p<0.05 was considered significant.

Results: No differences in age, sex (CG: 84/16 F/M, RA: 87/18 F/M), BMI and percentage of pre and postmenopausal women were found between groups. FN and TH BMD were significantly lower in RA patients mainly due to the RA+No-Biol group. TH BMD was significantly lower in RA+No-Biol vs CG (right TH BMD= CG: 0.935±0.117; RA+No-Biol: 0.852±0.133, -8.9%, p<0.0001; left TH BMD= CG: 0.801±0.117; RA+No-Biol: 0.728±0.118, -9,1%, p=0.0002). Consistent with TH, right and left FN BMD were lower in RA+No-Biol compared with CG. The RA-Biol only showed significant lower values in left FN compared with CG. The 3D analysis indicated that the AR+No-Biol has affected both trabecular and cortical bone (right trabecular vBMD= CG: 195.9±38.9, RA+No-Biol: 176.6±46.3, -9,8%, p=0.0097; right sDens= CG: 164.5±20.3, RA+No-Biol: 150.2±23.7, 8.7%, p=0.0001; right integral vBMD= CG: 339.0±51.8, RA+No-Biol: 307.5±63.6, -9.3%, p=0.0016). The RA+Biol group showed no significant difference compared to CG Control in all of the parameters examined.

Conclusions: 1. The areal BMD by DXA and the volumetric BMD were higher in RA patients under biological treatment. 2. The 3D analysis showed cortical and trabecular bone separately and could be a useful tool to detect early trabecular changes, a site mainly affected in RA patients. An additional analysis according to the activity and disease duration and cumulative glucocorticoids dose is required.

98

RHEUMATOID ARTHRITIS AND CORONARY HEART DISEASE: FEATURES OF COMORBIDITY

Roman Yatsyshyn¹, Bohdana Doskaliuk¹, Olexandra Hotsaniuk¹, Oleksandr Shtefiuk¹, Khrystyna Fedorovych¹, and Ivan Stoika¹. ¹SHEI "Ivano-Frankivsk National Medical University", Ivano-Frankivsk, Ukraine.

Objectives: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized not only by joint lesions but also by systemic inflammation of the internal organs. It is very common for patients with RA to have concomitant pathology. The aim was to investigate the interaction between the activity of RA and comorbid pathology using as example of coronary heart disease (CHD).

Methods: The research is based on data of 76 patients with documented diagnosis of RA. The diagnosis of RA was established in accordance with the ACR / EULAR 2010 criteria. The age of the examined patients ranged from 31 to 68 years, an average of 45.7 ± 7.3 years. Among the patients included in the study there were 27 (35,5%) men and 49 (64,5%) women. For determining disease activity DAS 28 index, erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (anti-CCP), rheumatoid factor (RF) and C-reactive protein (CRP) were used. Correlation analysis between RA clinical activity and severity of CHD. The severity of CHD was determined by classification of Canadian Cardiovascular Society (CCS). Statistical processing of the data was performed using Microsoft Excel software package and Statistica 8.0.

Results: During the examination of the existence of a correlation between the features of the clinical course of RA and the severity of CHD, it was determined that all the indicators selected for testing had a direct correlation with the severity of CHD. The strongest direct correlation was found between the ESR index and severity of CHD (r=0,73). The least pronounced was the correlation between CHD and the DAS 28 score (r=0,41). For other parameters a positive correlation with CHD severity was also found CHD: for CRP (r=0,63), for anti-CCP (r=0,56) and for RF (r=0,59).

Conclusions: There was a direct correlation between CHD severityand RA clinical features. So, it can be concluded that the expressed clinical and laboratory RA activity may be a predictor of the CHD development or progression. This can be explained by the presence of active systemic inflammation in the human body, which plays role in the pathogenesis of CHD.

99

PREVALENCE OF THE DIFFERENT ANTI-CARBAMYLATED PROTEIN ISOFORM ANTIBODIES IN FIRST-DEGREE RELATIVES OF PATIENTS WITH RHEUMATOID ARTHRITIS IN A LATIN AMERICAN POPULATION

Ana Sofía Leal Bramasco¹, César Vidal Elizondo Solis¹, Luis Eduardo Ramírez Monterrubio¹, Lorena Pérez Barbosa¹, David Vega Morales¹, Jorge Antonio Esquivel Valerio¹, Mario Alberto Garza Elizondo¹, Dionicio Ángel Galarza Delgado¹, and Karina Itzel González Márquez¹. ¹Servicio de Reumatología e Inmunología Clínica, Hospital Universitario "Dr. José Eleuterio González", Monterrey, Mexico.

Objectives: To establish the prevalence of the different isoforms of anti-Carmylated Protein (CarP) antibodies (IgA, IgM, IgG) in first degree relatives (FDRs) of patients with RA.

Methods: This is an observational descriptive cohort. Subjects underwent a complete physical examination, performed by a certified rheumatologist, which included clinical and serological measurements. The serological measurements included cyclic citrullinated peptide antibodies (CCPA), RF, and anti-CarP detected by ELISA using carbamylated fetal calf serum, according to Shin J et al with some modifications. The cut-offs for the anti-CarP IgA isoform was >125 U/mL, for the IgG isoform was >90 U/mL, and for the IgM isoform was >300 U/mL. The FDRs were classified as followed: suspicious arthralgia for progression according to the Van Steenvergen criteria; undifferentiated arthritis (UA) and RA according to ACR/EULAR 2010 classification criteria; and soft tissue rheumatic diseases.

Results: A total of 144 FDRs of 99 RA patients were enrolled. The demographic characteristics are shown in Table 1. The prevalence, as described in Table 2, for anti-CarP was 2.8% for the IgA isoform, 4.2% for the IgG, whereas IgM was not detected. The serologic associations were for RF/CCPA 4.48%, RF/anti-CarP 2.7%, RF 64.5%, CCPA 1.3%, CCPA/anti-CarP 0.69%, anti-CarP 3.4%, and no RF/CCPA/anti-Carp was observed.

According to the diagnostic classification, the group of suspicious arthralgia for progression included 2 subjects positive for the isoform IgG anti-CarP, the group of UA had 1 subject positive for the isoform IgA anti-CarP, albeit no isoform anti-CarP for the RA group was present. The soft tissue rheumatic diseases group had 5 subjects positive for the isoform IgG anti-CarP, while the asymptomatic group had 2 subjects positive for the isoform IgA anti-CarP.

Conclusions: Even though we used the 3 isoforms of anti-CarP antibodies, the prevalence of these antibodies in our cohort showed less positivity than in others.

102

EFFECTIVENESS AND SAFETY OF INFLIXIMAB, GOLIMUMAB AND GOLIMUMAB-IV IN RHEUMATOID ARTHRITIS FROM A LONGITUDINAL OBSERVATIONAL REGISTRY

Proton Rahman¹, Philip Baer², Denis Choquette³, Wojciech Olszynski⁴, Rafat Faraawi⁵, Louis Bessette⁶, Milton Baker⁷, Raman Rai⁸, John kelsall⁹, Larissa Lisnevskaia¹⁰, Jodie Reis¹¹, Keltie Anderson¹¹, Emmanouil Rampapakis¹², Odalis Asin-Milan¹³, Allen J. Lehman¹³, and Francois Nantel¹³. ¹Memorial University, St John's, Canada, ²Private practice, Scarborough, Canada, ³Montreal Rheumatology Institute, Montreal, Canada, ⁴University of Saskatchewan, Saskatoon, Canada, ⁵McMaster University, Hamilton, Canada, ⁶G.R.M.O. Inc., Quebec, Canada, ⁷Private practice, Victoria, Canada, ⁸Charlton Center, Hamilton, Canada, ⁹University of British Columbia, Vancouver, Canada, ¹⁰Private practice, Oshawa, Canada, ¹¹Private practice, Saskatoon, Canada, ¹²JSS Medical Research, Montreal, Canada, ¹³Janssen Inc., Toronto, Canada.

Objectives: To describe the profile of rheumatoid arthritis (RA) patients treated with infliximab (IFX), golimumab subcutaneous (GLM) or intravenous (GLM-IV) in Canadian routine care, along with its effectiveness and safety.

Methods: 1577 RA patients treated with IFX, GLM or GLM-IV were enrolled into the Biologic Treatment Registry Across Canada (BioTRAC) between 2006-2015, 2010-2017 and 2014-2017, respectively. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed with changes in TJC28, SJC28, MDGA, PtGA, pain, HAQ, and acute phase reactants. Safety was evaluated with the incidence of adverse events (AEs) and drug survival.

Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females were 75.7%- 77.1%, the mean age were 55.8-57.7 and the mean disease duration were 6.5-8.6 years. Most patients were bio-naive (> 80%).

Results: Treatment with IFX, GLM and GLM-IV significantly improved all disease parameters over time (p<0.001) from baseline to 6 months and up to 120, 78 and 42 months, respectively. The proportion of patients in SDAI remission at 12, 24 and 36 months reached 16.2%, 20.8% and 22.8% in IFX-patients; 34.7%, 47.5% and 52.7% in GLM-patients and 33.8%, 47.5% and 61.9% in GLM-IV-patients (p=0.1978 and p=0.0081 vs IFX).

AEs were reported for 61.5%, 67.4% and 59.2% (105, 113 and 82.6 events/100 PYs) and SAEs for 21.2%, 15.5% and 3.8% (11.7, 34.4 and 9.0 events/100 PYs) covering 2714, 1077 and 257 years of exposure for IFX, GLM and GLM-IV-treated patients, respectively. Eighteen, 7 and 1 deaths occurred among IFX-, GLM- and GLM-IV-treated patients, respectively.

The proportion of patients who discontinued treatment with IFX, GLM and GLM-IV were 74.0%, 52.8% and 42.5% over 3.0, 2.0 and 1.6 years, respectively.

Conclusions: In this real-world study of Canadian patients with RA, differences in baseline characteristics between patients treated with an anti-TNF over time and between agents shows potential selection biases when selecting a given therapy and may impact the proportion of patients achieving a target-specific outcome. Treatment significantly reduced disease activity and improved functionality in a similar fashion and were also safe and well tolerated.

104

FACTORS ASSOCIATED WITH FIBROMYALGIA IN PUERTO RICAN WOMEN WITH RHEUMATOID ARTHRITIS

Lilliana Serrano-Arroyo¹, Elizabeth Ramírez-Díaz², Franchesca Cruz-Pérez², Mariangelí Arroyo-Ávila², Ruth Fred-Jiménez², Noelia Rodríguez², Grissel Ríos², and Luis Vilá². ¹San Juan Bautista School of Medicine, Caguas, Puerto Rico, ²University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.

Objectives: Both rheumatoid arthritis (RA) and fibromyalgia (FM) are more common in women. However, the clinical differences between RA patients with and without FM are not well established, particularly for Hispanic populations. Therefore, we sought to determine the clinical factors associated with the coexistence of RA and FM in Hispanic women from Puerto Rico.

Methods: A cross-sectional study was conducted in an existingcohort of 377 women with RA. All patients had Puerto Rican ethnicity (self and four grandparents) and met the 1987 American College of Rheumatology (ACR) criteria for the classification of RA. Demographic parameters, health-related behaviors, RA clinical manifestations, disease activity (using the Disease Activity Score-28, DAS-28), functional status (using the Health Assessment Questionnaire, HAQ), patient’s and physician’s health assessments (using visual analogue scales), comorbidities, and RA pharmacologic therapy were studied between RA patients with and without FM. FM was ascertained per the 1990 ACR classification criteria. Data were examined using bivariate and multivariate regression analyses adjusted for age, alcohol consumption, cigarette smoking, and body mass index.

Results: The mean age of the study population was 55.7 years. Thirty (8.0%) patients had FM. Disease duration was similar in patients with and without FM (12.4 vs. 12.6 years, p=0.911). In the bivariate analyses, patients with FM were more likely to have higher HAQ (1.7 vs. 1.0, p=0.011) and patient’s global assessments of health (67.7 vs. 43.3, p=<0.001) and pain (69.2 vs. 44.5, p=<0.001) scores, and were more likely to have arterial hypertension (73.3% vs. 51.3%, p=0.020), asthma (20.0% vs. 6.3%, p=0.006), depression (43.3% vs. 11.2%, p=<0.001), and low back pain (30.0% vs. 15.0%, p=0.032). Conversely, patients with FM were less likely to achieve remission (10.3% vs. 20.3%, p=0.033), and to have joint deformities (43.3% vs. 63.1%, p=0.033) and radiographic evidence of joint damage (44.0% vs. 65.9%, p=0.029). In the multivariate analyses all variables, except for joint deformities and radiographic evidence of joint damage, retained significance.

Conclusions: In this group of Puerto Rican women with RA, patients with FM were less likely to achieve clinical remission, reported more pain and poorer general health, had more disability, and presented with more comorbidities such as arterial hypertension, asthma, depression, and low back pain than those without FM. The awareness of these disparities could help physicians in the evaluation and management of patients with coexistent RA and FM.

110

EXPERIENCE WITH RITUXIMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A THIRD LEVEL CARE HOSPITAL IN LIMA - PERU (2010 - 2017)

Cynthia Olarte Soto^1,2, and Wilkerson Pérez Medina³. ¹Clínica La Luz, Lima, Perú, ²Universidad Nacional Mayor de San Marcos, Lima, Perú, ³Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú.

Objectives: To describe the experience of rituximab users rheumatoid arthritis patients at a third care levelhospital in Lima - Perú.

Methods: Observational, descriptive and historical study. The review of the clinical histories of rituximab users was carried out between the period 2010 to 2017.

Results: 90 patients were included who met ACR classification criteria for rheumatoid arthritis and received rituximab between 2010 and 2017. All patients were female, with an average age of 57 years. Disease duration previous to the use of rituximab was 12.6 years. 100% of patients were RF (+) and had severe disease activity prior to the start of therapy. Rituximab was the first biologic agent in 72.2% of patients, the 2nd in 23.3% and the 3rd biological in 4.44%. The mean treatment duration was 4 years. Methotrexate was the previous DMARD used in 100%, and the previous combination most frequently used was Methotrexate and Leflunomide (16.6%). In 22 patients, no previous combinations of csDMARDs were used. 85.5% of rituximab users achieved disease remission/low activity. In 3% of patients, rituximab was discontinued due to noninfectious complications (neuropathy, uveitis and thyroid neoplasia). There were no adverse drug reactions.

Conclusions: The present study describes our experience with the use of Rituximab, confirming the efficacy and tolerability of this drug.

115

IMPLEMENTATION OF COMMUNITY EDUCATIONAL STRATEGIES BASED ON NEEDS IN THE INDIGENOUS QOM PATIENT POPULATION, SUFFERING RHEUMATOID ARTHRITIS IN ROSARIO CITY, ARGENTINA

Rosana Maris Quintana^1,2, Ana Bensi², Sofía Fernández², María de Lourdes Guggia², Andrés Honeri², Paola Iglesias², Stella Orzuza², Marcela Valdata², Ingris Pelaez-Ballestas^2,3, and Bernardo Pons-Estel^1,2. ¹Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR). Rosario, Rosario, Argentina, ²GLADERPO (Grupo Latinoamericano de Estudios de Enfermedades Reumáticas en Pueblos Originarios), Rosario, Argentina, ³Hospital General de México “Dr. Eduardo Liceaga”, Mexico City, México.

Objectives: To implement community-based indigenous educational health programs based on needs in a cohort of patients with Rheumatoid Arthritis (RA) of the Qom population in Rosario city, Argentina.

Methods: Qualitative study. The educational strategies were designed at a community level with the aim of disseminating knowledge about RA, its early detection and correct treatment; and at the individual level to ensure treatment continuity and patient follow-up. At the community level, workshops were implemented with the objectives: information about RA; identification of patients; information of the health care system and health loop of medical care; forms of treatment and help-seeking trajectory; strategies of the community to improve their quality of life. The final result was the collective production of an educational leaflet in Spanish language addressed to the Qom RA community. In the same way, workshops were also held to instruct on the benefits of obtaining disability certificates (DC) for patients with RA. At the individual level, follow-up and treatment adherence at the first level of health care through specialized consultation monthly were implemented.

Results: A total of 65 patients with RA were included in the community cohort. The patients’ mean (SD) age was 39.8 (1.6) yearsand 58 (89.2%) were female; mean number (SD) of years of formal education was 5.3 (0.3). 89.2% were seropositive, their mean (SD) disease duration was 110.5 (17.9) months and the median delay in diagnosis was 30.4 (IQR 52.8) months. The mean (SD) value of DAS-28 (ESR) was 4.8 (0.9). Moderate activity by DAS-28 (ESR) was present in the 67.6%. The 76.9% individuals reported HAQ-DI ≥ 0.8. The implementation of this educational strategies improved the follow up and treatment continuity of the patients. The consultation by specialists aimed at improving the links between the different levels of heath care, improved medical consultation times, and securing DCs with the help of professionals. As of today, 30 patients have obtained their DC.

Conclusions: The design and implementation of educational strategies based on needs improve patients follow-up and the links between level of care and the professional team. The role of different educational tools based on needs in vulnerable populations should be prioritized. The interdisciplinary approach enables the development of a network that promotes a genuine and true interculturality.

118

PREVALENCE OF LEUKOPENIA IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER TREATMENT WITH TUMOR NECROSIS FACTOR ALPHA INHIBITORS AND STUDY OF ITS ASSOCIATED VARIABLES

Leonela Lysseth Macias Oviedo¹, Marina Fornaro¹, Gisele Luna¹, Emilce Schneeberger¹, Rodolfo Pérez Alamino², Emilio Buschiazzo³, and Gustavo Citera¹. ¹Instituto de Rehabilitación Psicofísica, CABA, Argentina, ²Hospital Avellaneda, Tucumán, Argentina, ³Hospital Señor del Milagro, Salta, Argentina.

Objectives: To determine the prevalence of leukopenia in patients with RA treated with TNFi and to analyze its possible associated factors.

Methods: Cross-sectional study. We included patients ≥18 years of age with diagnosis of RA according to ACR/EULAR 2010 criteria who received TNFi therapy. The sociodemographic characteristics, comorbidities and their treatment, clinical characteristics of the disease, history of leukopenia before starting a TNFi and its causes were registered. The treatments before the onset of TNFi, date at the beginning of TNFi treatment, duration of treatment at the time of leukopenia, as well as measures of disease activity, laboratory data, concomitant treatment and adverse events at the time of leukopenia and 3 months prior were documented. For each patient with leukopenia, at least 5 control patients without leukopenia were matched by the duration of treatment with TNFi, to compare different demographic, clinical and therapeutic variables that could be associated with the development of leukopenia. Statistical analysis: Descriptive statistics. Chi square and Fisher's exact test. T test and ANOVA. Multiple logistic regression model (dependent variable: leukopenia).

Results: 169 patients with RA were included, with a median age of 59 years (IQR 50-66) and median disease duration of 13 years (IQR 8.5-19.7). A total of 11 patients had a history of leukopenia prior to the onset of TNFi. The median time of treatment with TNFi was 9 years. Sixteen patients developed leukopenia (9.5%) of whom 62% received Etanercept and 37% Adalimumab. The median time from the onset of TNFi to the presentation of leukopenia was 10 months (IQR 8-16). In the univariate analysis, patients who developed leukopenia had a longer disease duration [20.6 ±12.3 vs 14.8 ±9, p=0.02], higher frequency of leukopenia prior to the use of TNFi, (56.3% vs 5.2%, p=5x10-5) and history of leukopenia associated with the use of c-DMARD (25% vs 3.9%, p=0.008). In the multivariate analysis, only previous history of leukopenia remained significantly associated with leukopenia related with the use of TNFi (OR:44, CI95% 6.2-309, p=0.00001).

Conclusions: The prevalence of leukopenia in patients treated with TNFi was less than 10%. Previous history of leukopenia was the only variable independently associated with the TNFi related leukopenia.

124

CHANGE OF THERAPY IN PATIENTS WITH FAILURE TO INHIBITORS OF TUMOR NECROSIS FACTOR IN RHEUMATOID ARTHRITIS, DOMINICAN REPUBLIC

E Rosario-Guzmán¹, L Concepción-Sanchez¹, R Jiménez-Candelaria¹, M Marte-Robles¹, E Rodriguez-Bautista¹, V Rosario¹, R Muñoz-Louis¹, T Valdez-Lorie¹, and R Alba-Fériz¹. ¹Hospital Docente Padre Billini, Santo Domingo, Dominican Republic.

Objectives: To compare clinical outcomes between the use TNFi cycling (adalimumab, certolizumab pegol, golimumab, etanercep) versus switching to a new mechanism of action (tocilizumab, tofacitinib, rituximab) after failure secondary to a TNFi.

Methods: A medical records review, observational, cross-sectional study. Data from a cohort of patients from rheumatology service Hospital Docente Padre Billini in the period 2013-2018 were collected. Patients who met criteria EULAR / ACR 2010, with 3 consecutive consultations, who failed treatment with TNFi and changed were cycling or switching, the adjuvant use with DMARD and / or glucocorticoids. Activity was measured according to DAS28 after 6 months of continuous administration of the second drug. The data was analyzed with SPSS V23 for Windows 10.

Results: 227 meet the inclusion criteria. 32% (90) of the TNFi users and 26% (23) of them had a secondary failure. 91% (21) switches and 9% (2) TNFi cyclers. 57% (13) to tocilizumab, 26% (6) tofacitinib, 9% (2) rituximab, 4% (1) certulizumab pegol, 4% (1) adalimumab. Adalimumab was the one with the highest secondary failure with 39% (9), followed by etanercep 26% (6), 21% (5) and 13% (3) certolizumab pegol and golimumab, respectively. The decrease in DAS28 showed remission in 100% (2) of those treated with rituximab and in 54% (7) of tocilizumab 6 months after change, 67% (4) of users of tofacitinib were in low activity or remission, while patients treated with adalimumab and certolizumab pegol remained in moderate and high activity, respectively. The majority of 91% (21) used at least 5 mg of prednisone or its equivalent and 87% (20) used at least 12.5 mg of methotrexate.

Conclusions: Switching was much more frequent than cycling, showing lower DAS28 values and less requirement for glucocorticoids and DMARDs in the switching group, these results support the change to a new disease modifier after failure to TNFi.

131

EXPERIENCE OF TOFACITINIB, EPIDEMIOLOGICAL ASPECTS IN THE DOMINICAN REPUBLIC

L. Concepción-Sánchez¹, E. Rosario-Guzmán¹, M. Marte-Robles¹, R. Jiménez-Candelaria¹, R. Muñoz-Louis¹, V. Rosario¹, E. Rodríguez-Bautista¹, T. Valdez-Lorie¹, and A. Alba-Fériz¹. ¹Hospital Docente Padre Billini, Santo Domingo, Dominican Republic.

Objectives: To evaluate the efficacy and safety of tofacitinib in the rheumatology service at Hospital Docente Padre Billini.

Methods: Medical records review, cross-sectional study. Data were collected from the electronic medical records of the rheumatology service at Hospital Docente Padre Billini during the 2016-2018 period. All patients diagnosed with rheumatoid arthritis (RA) according to the ACR / EULAR 2010 criteria who are or have been treated with tofacitinib were included in the study. Patients with less than one month of treatment were excluded. The activity of the disease was measured with the DAS28 Score. The data was analyzed with SPSS V23 for Windows 10.

Results: 43 patients were included, 97.7% (42) women and 2.3% (1) men. 25.5% (11) patients were in remission, 30.2% (13) were in low activity, 32.5% (14) in moderate activity and 11.6% (5) in high activity. 46% (20) were on concomitant treatment with methotrexate. 16% (7) of the patients presented adverse events, 9.3% (4) dyslipidemia, 4.6% (2) skin rash, 2.3% (1) increase in liver enzymes, 2.3% (1) hypertriglyceridemia. 11.6% (5) presented a therapeutic failure.

Conclusions: More than 50% of the patients in treatment with tofacitinib presented good response to it, only 11.6% presented therapeutic failure. Dyslipidemia was the most frequent adverse effect followed by skin rash. No patient presented a severe adverse event.

132

OCULAR MANIFESTATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS FROM THE DOMINICAN REPUBLIC

Maria Alexandra Marte-Robles¹, R. Jiménez-Candelaria¹, E. Rosario-Guzmán¹, L. Concepción-Sánchez¹, R. Muñoz-Louis¹, V. Rosario¹, E. Rodríguez-Bautista¹, T. Valdez-Lorie¹, and R. Alba-Fériz¹. ¹Hospital Docente Padre Billini, Santo Domingo, Dominican Republic.

Objectives: To identify ocular manifestations in patients with rheumatoid arthritis of the Hospital Docente Padre Billini Rheumatology service

Methods: A descriptive cross-sectional study. Data were collected of a cohort from the Hospital Docente Padre Billini rheumatology service during the period 2013 to 2108. Inclusion criteria: all patients diagnosed with rheumatoid arthritis (RA) according to ACR/EULAR 2010. With 3 visits per year to the rheumatologist and at least 2 visits to an ophthalmologist. The activity of disease was evaluated by measuring the DAS 28. Demographic data and disease progression wereassessed. Exclusion criteria: patients with ocular manifestation attributed to other causes. Data were analyzed using SPSS V23 for Windows 10.

Results: 441 met the inclusion criteria for this study where 95.4% (420) women, 4.5% (20) men. Mean age 63.5 years. Five years ffom RA diagnosis : 10.2% (45) had Ocular manifestations; of them 37.7% (17) had secondary Sjogren's syndrome, 42.2% (19) had dry syndrome, 4.4% (2) had Necrotizing scleritis, 8.8% (4) had keratoconjunctivitis Sicca, 2.2 % (1) had scleritis, 4.4% (2) had glaucoma, of them 42.2 % (19) had moderate activity, 28.8% (13) had low activity, 17.7% (8) were in remission and 11.1% (5) had high disease activity

Conclusions: We found that 10.2% of our patients presented ocular manifestations, predominantly dry syndrome and Sjogren's syndrome; they were associated with a moderate disease activity; It is important to monitor patients globally and have a multidisciplinary team since these complications can lead to disability, being vital to maintain control of the disease in our patients.

134

RELATIONSHIP OF GLUCOSE LEVELS AND THE USE OF GLUCOCORTICOSTEROIDS AMONG PATIENTS WITH RHEUMATOID ARTHRITIS IN THE DOMINICAN REPUBLIC

Maria Alexandra Marte-Robles¹, R. Jiménez-Candelaria¹, I. Mercedes-Nuñez¹, E. Tejada-Reyes¹, R. Muñoz-Louis¹, V. Rosario¹, R. Peña-Blanco¹, T. Valdez-Lorie¹, and R. Alba-Fériz¹. ¹Hospital Docente Padre Billini, San Cristóbal, Dominican Republic.

Objectives: To evaluate the relationship of blood glucose levels and the use of glucocorticoids in patients with rheumatoid arthritis (RA).

Methods: Data were collected from digital medical records of the Hospital Docente Padre Billini Rheumatology service during the period of November 2017 - March 2018. Inclusion criteria: patients with a diagnosis of RA by ACR/EULAR 2010 criteria. Basal blood glucose and quarterly controls, use of glucocorticoids between 5 to 15 mg/day with a time greater than or equal to 8 weeks. Exclusion criteria: patients with a diagnosis of diabetes mellitus, use of GC greater than 15 mg/day. The data were analyzed using SPSS V23 Windows 10.

Results: 224 records met inclusion criteria. 96.4% (216) were women and 3.5% (8) men, with a median age of 56.1 years. 72.7% (163) had a baseline blood glucose < 110mg/dl, 27.2% (61) a baseline blood glucose > 110mg/dl. 3.1% (7) patients with blood glucose > 110mg/dl using 10-15 mg of prednisone, 6.6% (15) patients with blood glucose > 110mg/dl using 5-10 mg of prednisone and 87.9% (197) patients with blood glucose < 110mg/dl using 5-10 mg of prednisone.

Conclusions: Our study shows that there is a significant change on blood glucose levels with the use of GC at intermediate-action doses of 5 to 15mg. The monitoring of baseline glucose is important due to the risk of developing DM in those patients with a baseline glucose > 125 mg/dl.

142

RHEUMATOID ARTHRITIS ACTIVITY MEASURED BY DAS28-ESR AND ITS RELATIONSHIP WITH HEMATOLOGICAL VARIABLES

Oriela Martinez Hernandez¹, Sanshenka Bonilla Tovar¹, and Ivan Stekman. ¹Hospital Universitario De Caracas, Caracas, Venezuela.

Objectives: 1. Determine the activity of Rheumatoid Arthritis (RA) by DAS28-ESR.

2. Relate the hematological variables hemoglobin, hematocrit, leukocytes and platelets according to: risk factors, diet and medication used.

3. Evaluate which of the hematological variables is associated with the highest index of disease activity measured by DAS28-ESR.

Methods: This is an observational, analytical, cross-sectional study. In this sense, in the present investigation the population under study was constituted by patients diagnosed with RA who were care for at the Rheumatology service of the University Hospital of Caracas during the period 2016-2017. The inclusion criteria were patients who had a rheumatology consultation at the University Hospital of Caracas, with a diagnosis of RAaccording to the ACR 1987, any sex and age over 18 years and patients receiving any treatment for RA. The exclusion criteria were patients who were suffering from an infectious process, or with hematological disorders and / or neoplasms previously diagnosed and not related to RA.

Results: Almost half of the patients were in remission (48.4%), 19.4% in low disease activity, 25.8% in moderate disease activity and only 6.5% were onhigh activity.

The values of hematological variables such as hemoglobin, hematocrit, leukocytes and platelets were measured and their relationship with the degree of activity of the disease measured by DAS28-ESR were examined. Statistically significant results were observed with hemoglobin and hematocrit; lower values for both occur in patients with more active disease with an OR = 2.53 (95% CI: 1.01-6.33).

We determined the relationship between medications, risk factors, diet and hemoglobin values because it was the only statistically significant variable, showing that patients using steroids had lower hemoglobin values compared to patients who did not take them with a p = 0.019.

Conclusions: In view of the results obtained, it is concluded that hemoglobin and hematocrit are the hematological variables associated with disease activity measured by DAS28-ESR, with these levels not being influenced by other variables such as diet, risk factors and medication.

143

DEPRESSION AND ANXIETY IN PARAGUAYAN PATIENTS WITH RHEUMATOID ARTHRITIS

Astrid Paats¹, Susan Riquelme-Granada¹, Lourdes Román¹, Rodrigo Acosta¹, Nelson Ortíz¹, Marcos Vázquez¹, and Sonia Cabrera¹. ¹Hospital De Clínicas Paraguay, Asunción, Paraguay.

Objectives: To describe the clinico-epidemiological characteristics of patients with rheumatoid arthritis (RA and their relationship with the Hospital Anxiety and Depression Scale (HADS).

Methods: Descriptive, analytical, cross-sectional study in a cohort of Paraguayan patients with RA, from a third level hospital. The Hospital Anxiety and Depression Scale was used. It comprises two subscales (HADA: anxiety and HADD: depression) of seven items each with scores of 0 to 3 each. A score of 8 to 10 represents a possible case and >10 a probable case for both subscales. A questionnaire was completed with epidemiological variables (i.e. sex, age, schooling), clinical variables (i.e., disease duration, disease activity (DAS 28), comorbidities), laboratorial variables (rheumatoid factor, ACPA) and radiographic variables (erosions). The qualitative variables were expressed in frequencies and percentages and the quantitative variables as averages with their standard deviations. Chi square was used for qualitative variables andStudent’s t for quantitative variables. The statistical analysis was performed with the statistical program SPSS V.23.0.

Results: 92 patients were included. The average HADA score was 6.72 ± 4.4 and HADD score was 5.24 ± 4.20. 10.9% (10/92) of patients had anxiety (HADA case), 16.3% (15/92) had probable anxiety, while only 6.5% (6/92) had depression (HADD case), and 9.8% (9/92) had probable depression.

Regarding depression, in the HADD group we found a higher percentage of patients with 7 to 12 years of schooling (83.3 % vs. 16.4%, p 0.01), shorter disease duration (45.67 ± 40.49 vs. 118.27 ± 87.16 months, p= 0.047) and seropositive disease (66.6% vs. 33.4%, p=0.006).

In relation to anxiety, in the HADA group, patients were more frequently obese (60% vs. 40%, p=0.04), had shorter disease duration (60.8 ± 39.8 vs. 119.96 ± 88.74 months, p=0.041) and were seropositive (8% vs. 2%, p=0.067), while the probable HADA group was also more often obese (66.7% vs. 33.3%, p=0.019).

Conclusions: We found a low frequency of depression and anxiety in our established RA Paraguayan patients’ cohort. Patients with both anxiety and depression were more frequently seropositive and had a shorter disease duration. Among patients with anxiety, obesity is more common.

156

RHEUMATOID ARTHRITIS RECEIVING BIOLOGICAL TREATMENT IN GUATEMALA

Jose Manuel Benavente Larios¹. ¹Instituto Guatemalteco De Seguridad Social, Quetzaltenango, Guatemala.

Objectives: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, characterized by persistent inflammation of the joints, which typically affects the small joints of the hands and feet. At present, there is a wide variety of synthetic and biological disease modifying drugs. The aim of the present work is to know the percentage of patients treated with biological drugs, which was the indication for their initiation and which is the most used biological therapy.

Methods: The electronic clinical records of patients with a diagnosis of RA treated in the Medical Specialties Unit "Gerona" of the Guatemalan Social Security Institute were reviewed. The information collected was demographic data, date of disease diagnosis and the treatments received, detailing whetherbiological treatment had been initiated as monotherapy or associated to another DMARDs, the presence of intolerance or toxicity to DMARDs. For the statistical analysis, descriptive statistics were used expressing the continuous data as averages and standard deviation (SD) for the demographic data and percentages for the analysis of the treatment and causality data, in both cases the confidence interval was 95%.

Results: We included 636 RA patients; 97 of them were being treated with biological modifying drugs. The average duration of the biological treatment was 3.85 years, in 75% of the cases the biological treatment was initiated due to DMARD ineffectiveness. The most frequent biological drug used at the beginning was Infliximab (81.44%), in 51% of cases evaluated there was a change to another biologic drug; in 28.8% of these patients the switch was due to loss of efficacy, in 11.34% due to adverse events and in 7 patients due to lack of response since treatment initiation. Only 4 patients were treated with biologics as monotherapy, 93 patients receive biologics in combination with synthetic DMARDs; the combination of Methotrexate and Prednisone was the most frequent andwas used by 26.8% of patients, followed by the combination of methotrexate, prednisone and hydroxychloroquinewhich was used by 20.6% of the patients studied.

Conclusions: In the present study it was found that 15% of RA patients were being treated with biological drugs, this proportion being acceptable when compared with other series of cases. The average biological treatment duration was almost 4 years, but during that time more than half of the patients needed a change in their biological treatment, due in most cases to loss of efficacy; this finding probably relates to the frequent use of infliximab as a first line drug.

159

RELATIONSHIP BETWEEN DISEASE DURATION AND THE CLINICAL CHARACTERISTICS OF PARAGUAYAN PATIENTS WITH RHEUMATOID ARTHRITIS

Rodrigo Acosta¹, Lourdes Román¹, Susan Riquelme¹, Astrid Paats¹, Víctor Martinez¹, and Sonia Cabrera-Villalba¹. ¹Departamento de Reumatología, Hospital de Clínicas - Facultad de Ciencias Médicas, San Lorenzo, Paraguay.

Objectives: To describe the clinico-epidemiological characteristics of Paraguayan patients with established Rheumatoid Arthritis and their relationship with disease duration.

Methods: Descriptive, analytical, cross-sectional study of a cohort of patients with RA. The clinical records of patients in regular follow-up were reviewed and a questionnaire with epidemiological variables (sex, age, education, occupation), clinical (duration of the disease, extra-articular manifestations, activity of the disease), -laboratory (rheumatoid factor, ACPA) and -radiographic (presence of erosions) were completed. Disease duration was divided into four groups: 1.- Less than 1-year (<12 months), 2.- From 1 - 5 years (12-60 months), 3.- From 5 - 10 years (61 to 120) months) and 4.- More than 10 years (> 120 months). The qualitative variables were expressed in frequencies and percentages and the quantitative variables as averages with their corresponding standard deviations. Chi square was used for qualitative variables and Student's t for quantitative variables. The statistical analysis was carried out with the SPSS V.23.0 program, considering a significant p less than 0.05.

Results: We included 119 patients with the diagnosis of RA. When comparing the different variables between the groups we found some differences. Patients ingroup of 1-5 years: were younger (46.92 ± 15.23 years vs. 55.43 ± 10.75, p= 0.001), had a shorter diagnostic delay (11.33 ± 10.97 months vs 40.03 ± 39 months, p= 0.005), had lower frequency of hypertension (25.64% vs 74.36%, p=0.031), and lower frequency of erosions (23.53% vs 73.47%, p=0.015). We found important differences in the group with a disease duration of more than 10 years: mostly housewives (80% vs 20%, p=0.001), more often they required more than two DMARDs (57.78% vs 42.22%, p=0.09), had greater proportions of extra-articular manifestations (p=0.060), had a more erosive disease (58.53% vs 41.46%, p=0.02), as well as a longer diagnostic delay (50.87 ± 47 months vs. 18.3 ± 1.2 months, p=0.001).

Conclusions: In our cohort of Paraguayan patients with established RA, patients with a shorter disease duration were younger, had a shorter diagnostic delay, lower frequency of hypertension, while the group with the longer disease duration (> 10 years) had a longer diagnostic delay, most of them were not receiving compensation, needed a larger number of DMARDs and presented a more erosive disease.

160

SOLITARY FIBROUS TUMOR IN A PATIENT WITH RHEUMATOID ARTHRITIS. REPORT OF A CASE

Candido Flores¹, Dulce Karen Díaz Quintero¹, Rocío Chávez Mejía¹, Eliseo Pérez Silva¹, and Rafael García Rascón¹. ¹Hospital Regional De Alta Especialidad Ixtapaluca, Ciudad De México, Mexico.

Objectives: Introduction: The solitary fibrous tumor is a rare neoplasm that represents 8% of the benign neoplasms of the thorax and 10% of the pleural tumors. It is usually diagnosed as a finding, as almost all patientsremain asymptomatic. Data on clinical presentation, as well as natural history, are derived almost exclusively from medical recods series and case reports.

Objective: To report the presence of a solitary pleural tumor in a recently diagnosed rheumatoid arthritis (RA) patient.

Methods: A 38-year-old woman was sent to rheumatology for arthralgia and arthritis. After her evaluation, the diagnosis of seropositive rheumatoid arthritis (Rheumatoid factor 28.2 IU / ml, citrullinated cyclic peptide 92.3 IU) was made with severe activity (DAS-28 of 6.39)). As part of the protocol for the initiation of DMARDs, a chest X-ray film was requested, where a radiopaque, rounded image of 99.8 mm x 58.42 mm, with well-defined edges, separated from the diaphragm and not displaced, was found in the basal region of the right hemithorax. On a chest CT, mediastinum in, a solid tumor located in the middle lobe of the right hemithorax, of 106 x 90 x 101 mmwas observed, with reinforcement to the application of the contrast medium. Open thoracotomy and tumor resection were performed, the histopathological report is solitary fibrous tumor.

Results and Discussion We present the case of a patient with solitary fibrous tumor of pleural origin which was diagnosed as a finding when the protocol for the use of DMARDs was being done due to the recent diagnosis of RA.

The solitary fibrous tumor is a rare neoplasm, which originates in different serous membranes, being the main site the pleura. This tumor is often asymptomatic, although it may present with local symptoms such as cough, chest pain and dyspnea. Pleural effusion is not frequent. In some patients, paraneoplastic manifestations such as hypoglycemia occur. Survival for solitary pleura tumors varies from 75% to 100%. Most recurrences appear in the first 24 months after the resection; but they can occur, even after more than 15 or 20 years.

Conclusions: The pleural solitary fibrous tumor is an uncommon neoplasm with few case reports over time, it is usually asymptomatic, and diagnose as a casual finding on a chest radiograph as it was the case in our patient. The treatment of choice is complete surgical excision and, since the biological behavior of this tumor is unpredictable, the follow-up of cases should focus on the early detection of local recurrence or the appearance of metastasis. Follow-up has been carried out by oncology, so far without evidence of tumor recurrence.

162

RHEUMATOID ARTHRITIS AND ULCERATIVE COLITIS: A RARE ASSOCIATION

Candido Flores¹, Guillermo Eduardo Ramírez García¹, Rocío Chávez Mejía¹, and Rafael García Rascón¹. ¹Hospital Regional De Alta Especialidad Ixtapaluca, Ciudad De México, México.

Objectives: Introduction: chronic ulcerative colitis (UC) is a systemic disease of unknown etiology, but of an essentially autoimmune nature, can present with arthritis as an extraintestinal manifestation, being usually seronegative, although low rheumatoid factor (RF) titers can be found. The association with rheumatoid arthritis (RA) has rarely been documented.

Objective: to present a case report of a patient with coexistence of UC and RA.

Methods: Case: Man of 24 years. In 2016 whe developed mechanical arthritis of the right shoulder and later of the left shoulder. He wasdiagnosed in rheumatology with RA with seropositivity for anti-CCP antibodies at 216 IU / ml, arthritis of large and small joints. In 2018 he developed bilateral edema of both lower extremities upto the proximal third; he also had generalized pallor; treated with prednisone with partial response; he also developed bloody stools accompanied by anal itching and diffuse colic pain, as well as grade IV hypochromic microcytic anemia and thrombocytosis. A colonoscopy was performed which demonstrated lesions covered by fibrin of heterogeneous distribution, compatible with inflammatory bowel disease; biopsies were reported as intense chronic pancolitis with areas of ulceration and atrophy compatible with idiopathic chronic ulcerative colitis.

Results and Discussion The association of RA with other autoimmune diseases is common, being its major association with Sjögren's syndrome (50% of cases) and very rarely with inflammatory bowel disease (incidence 0.4-0.8%). Anti-CCP antibodies rarely occur in other autoimmune diseases different from RA, such as psoriasis and are directly related to smoking. The relationship between RA and UC has not been clearly defined, without genetic risk factors having been identified. It has been suggested that HLA-DR4 is a protective factor against UC, however, it plays a fundamental role in the pathogenesis of RA.

Conclusions: Although UC may present with extraintestinal manifestations at the joint level with low RF titers, coexistence with RA has been described rarely.

172

INTERSTITIAL LUNG DISEASE IMPROVEMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS AND TOFACITINIB

Hugo Javier Madariaga Charaja¹, Maria Elena Luza¹, and Dario Ponce de Leon. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: Report of three patients with Rheumatoid arthritis (RA) and severe intersticial lung disease (ILD) in whom tofacitinib achieved remission, clinical and tomographic improvements of ILD.

Methods: Case 1: November 2015, a 49-year-old man long standing RA with active disease. Was diagnosed with ILD with a CT scan on June 2015. Treatment included Leflunomide 20mg/d, Hydroxychloroquine 200 mg/d, azathioprine 50 mg/d, Prednisona 7,5 mg/d. On december 2015 treatment changed to tofacitinib 5mg BID and deflazacort 7.5mg/d.

Case 2: December 2016, 83-year-old woman long standing RA with active disease HAQ-DI 1.9 and DAS28 6.25. Present ILD diagnosed on June 2015. On nocturnal oxygen therapy. A High-resolution computed tomography (HRCT) showed multiple bilateral nodules and interstitial fibrotic striae type ‘ground glass’ more evident on the upper lobules. Treatment included Leflunomide 20mg/d, Sulfazalazine 2.5g/d and Deflazacort 7,5 mg/d.

Case 3: September 2017, 54-year-old woman long standing RA with active disease. A CT scan showed diffuse reticulous micro nodular infiltrate and honeycomb. Treatment included Leflunomide 20 mg/day, Prednisone 10 mg/day. Treatment was switched to tofacitinib 5mg twice daily as monotherapy.

Results: Case 1: Eight months later clinical improvement DAS 28: 3,25, HAQ DI: 1,13, VSG: 15, CRP 0,9 and there was no need for oxygen. New CT scan: Great decrease in interstitial tracts and lower number of honeycombs.

Case 2: December 2016 treatment changed to tofacitinib 5mg twice daily as monotherapy together with deflazacort 7.5mg/d and etoricoxib. Five months later the patient clinical condition improved considerably. DAS28 = 2.2 and HAQ = 0.7. Steroids were successfully discontinued. She no longer needed nocturnal oxygen therapy, and cough and dyspnea were substantially diminished. A new CT scan documented the reduction in size and density of ground glass area, as well as decreased interstitial tracts and number of nodules.

Case 3: 6 Months later patient clinical condition improved. A new CT scan documented the reduction in lesion size and density of ground glass area, as well as decreased interstitial tracts and number of nodules.

Conclusions: Tofacitinib is known to be effective in RAbut has not been studied for extra-articular manifestations.

- There is a report that it does not worsen Interstitial lung disease. We describe 3 patients in whom CT and symptoms improve, ideally it would be that in future descriptions lung function exams should be tested.

* There are CT images that confirm our result that would be added to the poster.

184

ADHERENCE TO TREATMENT WITH TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS

Tatiana Barbich¹, Osvaldo Luis Cerda¹, Emilce Edith Schneeberger¹, and Gustavo Citera¹. ¹Irep, Caba, Argentina.

Objectives: To evaluate the adherence to treatment with Tofacitinib in patients with Rheumatoid Arthritis (RA) using both versions of the self-adminiestered Compliance Questionnaire Rheumatology: CQR19 and CQR5. Secondary objectives were to determine the variables associated with adherence to Tofacitinib and to compare the performance of both questionnaires.

Methods: A cross-sectional study was carried out. We included patients ≥18 years of age, with a diagnosis of RA according to ACR-EULAR 2010 criteria under treatment with Tofacitinib. Sociodemographic data and clinical disease characteristics, such as disease duration, Rheumatoid Factor and anti-CCP status, ESR), CRP pain and global disease assessment by Numerical Visual Scale (NVS), joint count (28), DAS28, presence and duration of morning stiffness were recorded. Previous treatments, concomitant treatments, date and dose of Tofacitinib initiation, date of discontinuation and its reasons were recorded. All patients completed the CQR19 and CQR5 self-questionnaires. Statistical analysis: Descriptive statistics. T-test or Mann Whitney for the continuous variables, Chi square test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression in order to determine variables associated with adherence. A p ≤ 0.05 was considered significant.

Results: We included 52 patients, 82.7% women, with a median age (m) of 57.7 years, disease duration m 16 years. 63.5% had comorbidities and 27% were smokers. 65.4% had received b-DMARD prior to Tofacitinib. 86.5% of the patients treated with Tofacitinib used 5 mg BID and 48% received Tofacitinib as monotherapy. In 52% the concomitant treatment was: Methotrexate 63%, Leflunomide 33.3% and Sulfasalazine 3.7%. The median time of Tofacitnib treatment was 13 months. Only one patient permanently stopped treatment due to lack of drug availability. Median CQR19 was 89.5.44 patients (84.6%) had an adherence ≥ 80%. The variables significantly associated with adherence ≥ 80% were the presence of comorbidities (p = 0.014) and older age (p = 0.033). Using the CQR5, a similar percentage of patients (82.7%) were adherent, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with better treatment adherence.

Conclusions: The treatment adherence to Tofacitinib was very good for both presentiontations. Older age waassociated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low.

190

RELEVANT AUTOANTIGENS IN LATIN AMERICAN (CUBAN) RHEUMATOID ARTHRITIS PATIENTS

Goitybell Martínez¹, Bárbara Torres¹, Eugen Feist, Gerd-Rüdiger Burmester, Holger Bang, and Dirk Roggenbuck Roggenbuck. ¹Centro Nacional de Genética Médica, La Habana, Cuba.

Objectives: To characterize the reactivity of autoantibodies against a new citrullinated peptide of fibrinogen and carbamylated and citrulinated antigens of vimentin in relation to establish rheumatoid factor, second generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA.

Methods: A new citrullinated peptide of fibrinogen alpha chain designed by informatics prediction was synthesized. Antigenic properties of carbamylated vimentin and the citrullinated fibrinogen peptide were analyzed using an enzyme immunoassay in 81 patients with early RA, 81 patients with established RA, 81 patients with other rheumatic diseases and healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor (RF), anti-CCP2 and anti-mutated citrullinated vimentin (anti-MCV) antibodies.

Results: Prevalence of anti-citrullinated fibrinogen peptide (84%) anti-MCV (80%), anti-carbamylated vimentin (82%) antibodies were higher than the classical RF (44%) and anti-CCP2 (49%) in the early RA cohort. The higher prevalence was observed for anti-MCV (88%) and anti-carbamylated vimentin (86%) in patients with established RA. The best diagnostic performance (higher balance sensitivity/specificity) was achieved for anti-carbVIM antibodies in a RA cohort of this ethnic origin. Low clinical activity and remission were more frequently achieved in seronegative patients.

Conclusions: Our results support the model that citrullination and carbamylation may contribute unidirectionally to the pathogenesis of RA. The designed citrullinated fibrinogen peptide, carbamylated and citrullinated antigens of vimentin represent relevant autoantigens that optimize the strategy for autoantibody testing in Cuban RA patients and needs to be confirmed in other cohorts.

193

TWO-YEAR COST-UTILITY AND COST-EFFECTIVENESS ANALYSIS OF DIFFERENT COBRA LIKE INTENSIVE REMISSION INDUCTION STRATEGIES FOR EARLY RHEUMATOID ARTHRITIS: A PIGGY BACK STUDY ON THE PRAGMATIC RANDOMIZED CONTROLLED CARERA TRIAL

Sofia Pazmiño Lucio¹, Annelies Boonen², Rene Westhovens^1,3, Veerle Stouten¹, Johan Joly¹, Diederik De Cock¹, Kristien Van der Elst³, and Patrick Verschueren^1,3. ¹Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium, ²Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre, Maastricht, Netherlands, ³Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.

Objectives: To evaluate if methotrexate (MTX) with a moderate step-down glucocorticoid (GC) scheme (COBRA Slim) is cost-effective compared to other treatment strategies in a treat-to-target setting for patients with early rheumatoid arthritis (RA).

Methods: A cost-effectiveness analyses from healthcare perspective was performed alongside the 2-year open-label pragmatic randomized controlled CareRA trial. 379 DMARD naïve early RA patients were stratified into high-(n=289) and low-risk (n=90) groups based on classical poor prognostic markers and then randomised to 1/4 treatment strategies: MTX monotherapy with (COBRA Slim) or without a moderate step-down GC scheme (TSU) or combination of classical synthetic DMARDs with either a high (COBRA Classic) or moderate step-down GC scheme (COBRA Avant Garde). Slim was compared to Classic and Avant Garde in the high-risk group and to TSU for the low-risk group. Health care utilization was extracted from electronic trial records. Effectiveness was assessed as the proportion of patients in remission (SDAI≤3.3) at year 2 and mapped quality-adjusted-life-years. Due to skewed data, the non-parametric Mann-Whitney U or Kruskal Wallis tests for continuous variables and Chi square corrected with bootstrapping for categorical variables were used.

Results: The results of the base-case cost-utility analysis (intention-to-treat) revealed COBRA Slim is numerically less expensive (k€ 4.13) for high-risk patients compared with COBRA Classic (k€5.97) and COBRA Avant Garde (k€5.14) (p=0.187) and had no significant difference in quality-adjusted-life-years (QALYs)(p=0.604). COBRA Slim is not statistically significantly more expensive (k€5.03) than TSU (k€4.98) for low-risk patients (p=0.932) but with a significant gain in QALYs (+0.14; p=0.035). In terms of SDAI remission, COBRA Avant Garde had more patients (45%) reaching remission than COBRA Slim (29%)-p=0.017. In the low risk group, 44% of COBRA Slim and 28% of TSU patients reached remission (p=0.102).

Conclusions: COBRA Slim is a cost-effective, feasible initial treat-to-target strategy for patients with early RA regardless of classical poor prognostic markers. In the high-risk group, COBRA Slim has a similar quality of life compared to more intensive combination strategies. For the low-risk group, COBRA Slim yields significantly better quality of life and disease control in comparison to the traditional step-up approach. Thus, even patients estimated to have a good prognosis seem to benefit greatly from a more intensive strategy with GCs.

196

SAFETY PROFILE OF BARICITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS UP TO 6 YEARS: AN UPDATED INTEGRATED SAFETY ANALYSIS

Mark Genovese¹, Josef Smolen², Tsutomu Takeuchi³, Terence Rooney⁴, Christina Dickson⁴, Xiao-Yan Yang⁴, Chadi Saifan⁴, Anabela Cardoso⁴, Maher Issa⁴, Taeko Ishii⁵, Kevin Winthrop⁶, and Diana Gómez. ¹Stanford University Medical Center, Palo Alto, CA, USA, ²Medical University of Vienna, Vienna, Austria, ³Keio University, Tokyo, Japan, ⁴Eli Lilly and Company, Indianapolis, IN, USA, ⁵Eli Lilly and Company, Kobe, Japan, ⁶Oregon Health Sciences University, Portland, OR, USA.

Objectives: Baricitinib (bari), an oral, selective inhibitor of Janus kinase (JAK) 1 and JAK 2, is approved for the treatment of moderately to severely active RA in adults in over 50 countries including European countries, US and Japan. We further describe the drug’s safety profile with updated data from an ongoing long-term extension (LTE) study.

Methods: Long-term safety of once-daily bari was evaluated in the “all-bari-RA” dataset, which includes all patients (pts) with active RA exposed to any bari dose from 8 randomized trials (4 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 LTE study (data up to 01-April-2017). Previous all-bari-RA analyses1 are provided for comparison (data up to 10-Aug-2015 and 01-Sept-2016).2 Dose responses were evaluated based on the 4 Phase 2/3 trials in which pts were randomized to 2 or 4mg including data from the LTE (the “2mg-4mg-extended” dataset). Data were censored at rescue or dose change (as-treated analysis). Because of the latent period for malignancy, 2mg-4mg-extended was also analyzed without censoring for rescue or dose change (as-randomized analysis). Incidence rates (IR) per 100 patient-years (PY) were calculated.

Results: In the current analysis, 3492 pts received bari for 7860 total PY of exposure (an increase in over 1200 PY; 18% from 01-Sept-2016) for up to 6 years. Of these, 2723 (78.0%) were treated for at least 52 weeks and 1788 (51.2%) were treated for at least 130 weeks. Adverse events (AEs) IRs did not increase with prolonged exposure. Malignancy (excluding non-melanoma skin cancer (NMSC)) IR were 0.5 and 1.2 for 2mg and 4mg, respectively, with as-treated analysis and 0.8 and 0.8 with as-randomized analysis. For the above events, the current IRs in all-bari-RA are similar to those previously reported. The following IRs were observed in the current all-bari-RA: gastrointestinal (GI) perforation (0.04), and tuberculosis (TB) (0.14). Fewer than 1% of pts discontinued due to abnormal lab results.

Conclusions: In this updated integrated analysis of patients with moderately to severely active RA, including patients exposed for up to 6 years, baricitinib maintained a safety profile that was similar to that previously reported (1,2) acceptable in the context of demonstrated efficacy (3,4).

References:

1. Smolen JS et al. Ann Rheum Dis 2016:75(Suppl 2):243-4.

2. Genovese MC et al. Arthritis Rheumatol. 2017;69(suppl 10).

3. Taylor PC et al. NEJM 2017:376:652-62.

4. Genovese Mc et al. NEJM 2016:374:1243-52.

198

FREQUENCY AND DURATION OF EARLY NON-SERIOUS ADVERSE EVENTS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB 5 MG TWICE DAILY AS MONOTHERAPY AND COMBINATION THERAPY

Ara Dikranian¹, Jürgen Wollenhaupt², Valderilio F Azevedo³, Louis Bessette⁴, David Gold⁵, Jose Luis Rivas⁶, Harry Shi⁷, Lisy Wang⁸, John Woolcott⁷, Andrea Shapiro⁹, and Peter Nash¹⁰. ¹Cabrillo Center for Rheumatic Disease, San Diego, USA, ²Schön-Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg, Germany, ³Universidade Federal do Paraná, Curitiba, Brazil, ⁴Laval University, Kirkland, Canada, ⁵Pfizer Canada, Montreal, Canada, ⁶Pfizer SLU, Madrid, España, ⁷Pfizer Inc, Collegeville, USA, ⁸Pfizer Inc, Groton, USA, ⁹Pfizer Inc, Peapack, USA, ¹⁰University of Queensland, Brisbane, Australia.

Objectives: Tolerability remains ill-defined in clinical trials and most commonly refers to non-serious adverse events (AEs) that may impact patient satisfaction and treatment adherence. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This update to a previously reported post hoc analysis¹ describes the frequency and duration of the most commonly reported non-serious AEs related to tolerability in patients with RA receiving tofacitinib 5 mg twice daily (BID) as monotherapy or in combination with conventional synthetic (cs)DMARDs in Phase (P)3 and P3b/4 studies.

Methods: Data were pooled from the following studies of tofacitnib in patients with moderate to severe RA: ORAL Step (NCT00960440); ORAL Solo (NCT00814307); ORAL Scan (NCT00847613); ORAL Sync (NCT00856544); ORAL Standard (NCT00853385); and ORAL Strategy (NCT02187055). This analysis included data from patients receiving tofacitinib 5 mg BID monotherapy (ORAL Solo, ORAL Strategy), placebo (PBO; ORAL Solo), or tofacitinib 5 mg BID or PBO with csDMARDs (all studies except ORAL Solo). Non-serious AEs (defined as AEs affecting patients’ day-to-day experience and ability to tolerate treatment) with an incidence rate (IR, patients with events per 100 patient-years [PY]) ≥5 were evaluated up to Month 3. Infections, laboratory test abnormalities, general disorders, or events not reported directly by patients, and musculoskeletal events likely due to underlying RA, were excluded, to focus on AEs that could impact treatment adherence.

Results: Of the 2657 patients included in the analysis; 1976 received tofacitinib 5 mg BID (monotherapy: N=627; combination: N=1349); 681 received PBO (monotherapy: N=122; combination: N=559). Up to Month 3, the most frequently reported non-serious AEs which met the search criteria were headache, diarrhea, nausea, vomiting, dyspepsia, and abdominal pain upper; IRs ≥10 were observed for headache and diarrhea (tofacitinib 5 mg BID monotherapy, combination therapy and PBO monotherapy), and nausea (PBO monotherapy and combination therapy). Duration of AEs was ≤4 weeks for the majority of patients experiencing headache, diarrhea, or gastric discomfort (defined as any gastrointestinal pain, dyspepsia, epigastric discomfort, or abdominal discomfort or pain). Overall, in patients receiving tofacitinib 5 mg BID and PBO, respectively, 43.2% and 64.7% experienced headache; 66.1% and 81.3% experienced diarrhea; and 36.2% and 58.6% experienced gastric discomfort, for ≤2 weeks. The majority of AEs were mild or moderate.

Conclusions: Overall, non-serious, non-infectious AEs were mild or moderate and self-limiting. The frequency of non-serious AEs was comparable for patients receiving tofacitinib as monotherapy, or in combination with csDMARDs, and was generally similar for patients receiving tofacitinib compared with patients receiving PBO.

References:

1. Dikranian A et al. Arthritis Rheumatol 2013; 65: S192.

202

TOFACITINIB IN RHEUMATOID ARTHRITIS: AN UPDATED ANALYSIS OF REAL-WORLD DATA IN LATIN AMERICA

Estuardo Anzueto¹, Silvia María Rivera¹, Cecilia Asnal², Luis Javier Cruz³, Tomas Caicedo⁴, Oscar Felipe⁵, Rosa Maria Ventura⁶, María del Rosario Maliandi⁷, Jaime Hadid⁸, Roberto Huamanchumo⁹, and Dario Ponce de Leon¹⁰. ¹Clinica de Diagnóstico y Tratamiento de Enfermedades Reumatológicas y Musculoesqueléticas, Ciudad de Guatemala, Guatemala, ²Reumatología, Instituto Centenario, Buenos Aires, Argentina, ³Centro Médico San Francisco, Reynosa, Tamaulipas, México, ⁴Centro de Reumatología y Enfermedades del Tejido Conectivo, San Juan de Pasto, Nariño, Colombia, ⁵Reumatología, Clínica Las Vegas, Medellín, Colombia, ⁶Servicio de Reumatología, Hospital Metropolitano de Quito, Quito, Ecuador, ⁷Reumatología, Sanatorio Garay, Santa Fe, Argentina, ⁸Orto Alfa, Mexico City, México, ⁹Reumatólogo, Clinica Stella Maris, Lima, Perú, ¹⁰Pfizer Inc, Lima, Perú.

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). It is administered as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). A previous analysis characterized patients with RA who initiated tofacitinib and assessed the safety of tofacitinib in a real-world Latin American (LA) setting. ¹Here, we provide an updated analysis involving a larger patient population across more LA countries.

Methods: All adult patients with RA who initiated tofacitinib from 29 private/public centers in 10 countries (Argentina, Brazil, Chile, Colombia, Dominican Republic, Ecuador, Guatemala, Mexico, Panama, Peru) were considered for inclusion in this observational analysis. Data were obtained via a standardized format focusing on demographics, drug history, adverse events (AEs), AEs of special interest, latent tuberculosis (TB) screening (positive purified protein derivative or QuantiFERON-TB Gold), selected confirmed laboratory abnormalities (defined in terms of increases above upper limit of normal [ULN], or cell counts <500 cells/mm³), and discontinuation rates.

Results: In 582 patients (90.9% female), mean age was 51.8 years, mean disease duration was 10.5 years, and mean tofacitinib exposure was 13.6 months (659.6 total patient-years). Tofacitinib treatment was post-csDMARD in 51.5% of patients, post-1 biologic DMARD (bDMARD) in 21.6%, and post-≥2 bDMARDs in 26.8%; 39.3% of patients received tofacitinib monotherapy and 60.7% of patients received tofacitinib with csDMARDs. Of the 42/548 patients (7.7%) vaccinated against herpes zoster (HZ) before starting tofacitinib, none developed HZ. Of 40/548 patients (7.3%) with latent TB, none developed TB infections. 90 AEs, 9 serious infections, 18 HZ AEs (none multidermatomal, serious or severe), 1 malignancy (thyroid cancer), and 1 opportunistic infection (TB) occurred. Elevations >3 × ULN of liver enzymes, increases of creatine phosphokinase >ULN, and cytopenias (<500 cells/mm³) were infrequent (≤1%). Tofacitinib was withdrawn in 86 (14.8%) patients due to lack of efficacy (n=43; 7.4%), AEs (n=27; 4.6%), or other reasons (n=16; 2.7%).

Conclusions: In this analysis of real-world LA data, almost 40% of patients starting tofacitinib received monotherapy and around half were using tofacitinib as second-line treatment post-csDMARD failure. Safety appeared consistent with that of approved bDMARDs; ² there were no new safety concerns versus clinical trials of tofacitinib in LA patients with RA.³ However, the analysis is limited by the small sample size and limited exposure follow-up.

References:

1. Schneeberger EE et al. J Clin Rheumatol 2018; 24: S1–S174. Abstract 195.

2. Ahadieh S et al. Arthritis Rheum 2012; 64: S726.

3. Castañeda OM et al. J Clin Rheumatol 2017; 23: 193–199.

208

EXPERIENCE OF THE USE OF BIOLOGICAL THERAPIES IN A URUGUAYAN CENTER OF RHEUMATOLOGY: DATA FROM THE BIOBADAGUAY REGISTRY

Darwin Cordovilla^1,2, Daniel Palleiro^1,2, and Paloma De Abreu³. ¹Instituto Nacional De Reumatología Del Uruguay, Montevideo, Uruguay, ²Sociedad Uruguaya de Reumatología, Montevideo, Uruguay, ³Sociedad Paraguaya de Reumatología, Asunción, Paraguay.

Objectives: Biobadaguay is the Paraguayan-Uruguayan register of adverse effects in patients with inflammatory rheumatic diseases undergoing treatment with biological agents. The National Institute of Rheumatology of Uruguay (INRU) is the national reference center, part of the Biobadaguay register, which collects and updates information of this database.

The objective of this study is to analyse safety, survival and withdrawal causes among patients of the Biobadaguay database.

Methods: Observational, descriptive and longitudinal study in patients being followed up at INRU and included in Biobadaguay. Biological therapies, withdrawal causes, and adverse effects emergence were registered and analyzed. For the descriptive analysis, mean frequencies and percentages with standard deviation were used.

Results: Mean age was 50,9±11,6 yrs., 79% were female. Most common diagnosis was rheumatoid arthritis (67,9%), followed by psoriatic arthritis (15,7%) and ankylosing spondylitis (12,7%). 181 treatments were done with (47,5%) adalimumab, (24,3%) etanercept. (11,6%) rituximab, (7,7%) infliximab, (5,5%) golimumab and (3,3%) tocilizumab. The number of withdrawals registered was 73. Causes of the drop-out found were: (46,6%) inefficacy/loss of efficacy, (28,8%) adverse effects, (9,6%) loss of contact with patient and 4,1% were due to pregnancy. Mean survival of biological therapies was 20,3±19,6 months. There were 154 cases of adverse effects (adalimumab 48,7%; etanercept 24,6%); 128 mild and 26 severe: 15 infections, 4 interstitial lung disease, 2 gastrointestinal malignancies, 2 uveitis, 1 severe lymphopenia, myasthenia gravis and myocardial infarction. Infection was the most frequent adverse effect in 55,8% of cases (27,8% respiratory, 10,4% genitourinary and 8,4% skin infections). Other adverse effects were: hematologic (6,5%), skin (5,2%); hepatobiliary (5,2%); respiratory (4,5%) cardiovascular (4,5%).

Conclusions: Rheumatoid arthritis was the most frequent diagnosis and adalimumab the most used treatment. Main causes of drop-out were inefficacy and loss of efficacy. Biological therapies that were discontinued, had been used for about 20 months. Most of the adverse effect were mild, with infection being the most frequent, mainly respiratory, genitourinary and cutaneous infections.

213

RISK MANAGEMENT INDICATORS IN PATIENTS WITH RHEUMATOID ARTHRITIS. AN EXPERIENCE IN COLOMBIA

Julieth Carolina Castillo Cañon¹, Juan Camilo Fuentes Pachon¹, Paula Ximena Ramirez Barbosa¹, Ana Milena Gil¹, Paul Alejandro Mendez Patarroyo², and Lizbeth Acuña¹. ¹Cuenta De Alto Costo, Bogotá D.C, Colombia, ²Sociedad Colombiana de Reumatología, Bogotá, D.C., Colombia.

Objectives: To define, based on the evidence, the priority indicators for the evaluation and monitoring of risk management performed by insurance companies and health services providers, in people with rheumatoid arthritis (RA) in Colombia.

Methods: A formal consensus was carried out using an adaptation of the RAND-UCLA Appropriateness Methodology. It included five steps: 1. Extended literature review, 2. Preselection of indicators, 3. Judgement of the preselected indicators in two individual virtual voting rounds by a panel of experts, using a Likert scale (1 to 9), with previous discussion of each indicator, 4. Round of voting in a face-to-face meeting of the panel, to establish the final indicators, 5. Presentation of the results to the actors involved in the Colombian health system. Consensus was established when an indicator obtained 50% or more votes in the range of 7 - 9. The indicators that reached consensus were taken to the next round of voting, otherwise, they were excluded. Those who reached consensus in the face-to-face voting round were selected as final indicators.

Results: The panel was constitutedby 29 experts, including representatives from insurers, government, patients and clinical experts. The literature review identified 17 preliminary indicators that were submitted to the first round of virtual voting, reaching consensus in its entirety. In this round, an additional preliminary indicator was included. In the second round of virtual voting two indicators were excluded and 16 reached consensus. In the face-to-face voting round 14 final indicators were defined (12 process indicators and 2 result indicators): time to the attention by specialist; time from diagnosis to the beginning of treatment; measurement of anti-citrulline antibodies, rheumatoid factor, CRP and ESR; radiographic evaluation of hands and feet; screening for tuberculosis, initiation of treatment, simultaneous use of methotrexate and folic acid, being seen by occupational therapy or physical therapy, monitoring of disease activity; and achievement of remission or low activity.

Conclusions: Priority indicators were established to evaluate and monitor the risk management performed on patients with RA by insurers and health service providers through a formal consensus based on evidence, which involved the participation of different actors of the health system. The defined indicators cover the entire continuum of care and can be measured from information available in the Colombian health system, which can contribute to the development of improvement plans for the country, oriented to achieve a better quality of care and successful results in health.

214

PROMIS PAIN INTERFERENCE 6B AND FATIGUE 7A SHORT FORMS AND PROFILE-29 IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TNF INHIBITORS

Clifton O Bingham¹, Sergio Schwartzman², Shelly Kafka³, Dennis Parenti³, Shawn Black³, Stephen Xu⁴, Wayne Langholff⁴, and Jeffrey Curtis⁵. ¹Johns Hopkins University, Baltimore, USA, ²Weill Cornell Medical College, New York, USA, ³Janssen Scientific Affairs, LLC, Horsham, USA, ⁴Janssen Research & Development, LLC, Spring House, USA, ⁵University of Alabama at Birmingham, Birmingham, USA.

Objectives: PROMIS was used in rheumatoid arthritis (RA) patients (Pts) to assess disease activity across multiple domains (i.e. physical function, fatigue, pain interference). AWARE is an ongoing Phase 4 study assessing real-world use of intravenous Tumor Necrosis Factor inhibitor (TNFi) medications for RA. The study utilizes PROMIS and Clinical Disease Activity Index (CDAI) to assess effectiveness. Select PROMIS measures were analyzed to assess (1) relationship between baseline (BL) CDAI and PROMIS-scores, (2) responsiveness of PROMIS after initiation of TNFi and (3) relationship between PROMIS T-scores of the 4 item Profile 29v2 Fatigue and Pain Interference domains and respective PROMIS Short Forms (SF).

Methods: AWARE is a longitudinal, noninterventional, 3-year study at 100 US sites. RA pts were enrolled when initiating TNFi treatment. Treatment decisions are at the discretion of the treating rheumatologist. We report data from pts’ BL PROMIS Pain Interference 6b (PI), Fatigue7a (F), Physical Function, and CDAI. PROMIS T-scores were compared across CDAI disease category (high, moderate, etc) using ANOVA. We dichotomized pts based on whether their BL T-score was within 0.5 SD of the population mean (i.e. ‘normal’) or not, to evaluate effect modification in the subsequent change in PROMIS T-scores. Data shown are mean ± SD.

Results: Pts (N=1220) were 59.5 ± 13.2 years, disease duration 8.2 ± 9.9 years, 83.4% female, BMI 31.4 ± 8.51, BL CDAI 32.4 ± 15.6. A significant relationship between PROMIS T-scores (PI, F) and BL CDAI activity was confirmed. Among pts with BL PF T-scores <45, T-scores changed 1.4 and 2.4 units at infusions 2 and 5. Among pts with BL F scores >55, T-scores changed -2.5 and -3.6 units at infusions 2 and 5. Among pts with BL PI scores >55, T-scores changed -3.0 and -4.0 units at infusions 2 and 5. T-score changes were minimal in pts with BL PI and F T-scores ≤55 and PF ≥45 over 5 infusions; maximum T-score change was -0.7. Depending on domain, 14.7-27.3% of pts had initial PROMIS T-scores within 0.5 SD of normal. There was a significant (p<0.0001) relationship between PI and F T-scores and the respective 4 questions on the P29v2.

Conclusions: Avoiding floor effects in pts who initiated TNFi therapy with near-normal PROMIS scores, PROMIS instruments demonstrated a robust T-score change in response to initiation of TNFi therapy.

216

UNITED STATES RHEUMATOLOGY PRACTICE-BASED REAL-WORLD EVIDENCE OF METHOTREXATE UTILIZATION AND RESPONSE TO THERAPY IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH INTRAVENOUS GOLIMUMAB

Aaron Broadwell¹, Vance Bray², Douglas Conaway³, Joy Schechtman⁴, Alan Kivitz⁵, Dennis Parenti⁶, Shawn Black⁶, Stephen Xu⁷, Wayne Langholff⁷, and Shelly Kafka⁷. ¹Rheumatology and Osteoporosis Specialists, Shreveport, USA, ²Denver Arthritis Clinic, Denver, USA, ³Carolina Health Specialists, Myrtle Beach, USA, ⁴Sun Valley Arthritis Center, Peoria, USA, ⁵Altoona Arthritis & Osteoporosis Center, Altoona, USA, ⁶Janssen Scientific Affairs, LLC, Horsham, USA, ⁷Janssen Research & Development, LLC, Spring House, USA.

Objectives: AWARE (Comparative and Pragmatic Study of Golimumab IV Versus Infliximab in Rheumatoid Arthritis) is an ongoing Phase 4 comparator study designed to provide real-world assessment of intravenous golimumab (GLM) and intravenous infliximab (IFX) in patients (pts) with rheumatoid arthritis (RA). The primary objective is to assess the incidence of infusion reactions; concomitant use of methotrexate (MTX) is also reported. The FDA-approved GLM label states that it is indicated for the treatment of pts with moderately to severely active RA in combination with MTX; however prospectively obtained real world data on GLM use without MTX has not been reported.

Methods: AWARE is a longitudinal, noninterventional, observational, multicenter 3-year study conducted in the US. RA pts (1,200 adults) were enrolled at the time of initiating treatment with GLM or IFX. All treatment decisions including MTX utilization are made at the discretion of the treating rheumatologist. We compared patient demographics, disease characteristics, response to therapy, and discontinuation of GLM-treated pts with and without concomitant MTX from an interim analysis (IA) of the AWARE study. Imputations of CDAI data were not performed at this IA. Data shown are mean ± standard deviation.

Results: Among 678 GLM pts, 487 (71.8%) were GLM Plus-MTX and 191 (28.2%) were GLM No-MTX. Mean age, disease duration, baseline CDAI, weight, and BMI were similar in both groups as were the proportions of pts by sex and race. Response to therapy was assessed with CDAIs. Overall, 92.6% of GLM Plus-MTX and 91.5% of GLM No-MTX pts had a baseline (BL) categorical CDAI disease activity of moderate or high, and 7.4% of GLM Plus-MTX and 8.5% of GLM No-MTX pts had a BL disease activity of low or remission. At 3 and 6 months, the CDAIs were similar for the Plus-MTX and No-MTX groups (at 3 months, 21.3 and 20.7, respectively; at 6 months, 19.4 and 18.1, respectively). Discontinuation from the study during the period of this IA was similar between the GLM Plus-MTX (173/487; 35.5%) and GLM No-MTX (64/191; 33.5%). 7.9% of GLM No-MTX pts reported leflunomide use.

Conclusions: At BL 28.2% of pts on GLM did not report concomitant MTX use. The demographics of the GLM Plus-MTX pts did not differ remarkably from GLM No-MTX pts. The reported early response to treatment, assessed by CDAI score after 3 months and 6 months was similar in the GLM Plus-MTX and GLM No-MTX groups. These preliminary IA data suggest that in a real-world rheumatology practice setting, use of GLM with or without concomitant MTX led to similar CDAI scores at 3 and 6 months in RA pts with predominantly moderate to high BL CDAI disease category.

223

UPADACITINIB AS MONOTHERAPY: A PHASE 3 RANDOMIZED CONTROLLED DOUBLE-BLIND STUDY IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND INADEQUATE RESPONSE TO METHOTREXATE

JS Smolen¹, S Cohen², P Emery³, W Rigby⁴, Y Tanaka⁵, Y Zhang⁶, A Friedman⁶, AA Othman⁶, HS Camp⁶, and AL Pangan⁶. ¹Medical Univ of Vienna, Vienna, Austria, ²Metroplex Clinical Research Center, USA, ³Leeds Inst of Rheumatic & Musculoskeletal Medicine, Leeds NIHR BRC, UK, ⁴Dartmouth College, USA, ⁵Univ of Occupational and Environmental Health, Kitakyushu City, Japan, ⁶AbbVie, USA.

Objectives: Upadacitinib (UPA), a potent JAK inhibitor, with preferential activity against JAK-1, showed efficacy in rheumatoid arthritis (RA) patients with an inadequate response to csDMARDs or bDMARDs on continuing stable doses of csDMARD. Safety and efficacy of switching to UPA 15mg or 30mg monotherapy vs continuing methotrexate (MTX) as a blinded study drug was evaluated in patients with inadequate response to MTX (MTX-IR).

Methods: Patients with active RA (TJC≥6, SJC≥6, hsCRP≥3 mg/L) on stable MTX doses were enrolled. At Baseline (BL), patients were randomized 1:1:1 in a double-blind manner to receive once-daily (QD) UPA 15mg or 30mg monotherapy or to continue MTX (cMTX) at their prior stable dose but given as a blinded study drug. At BL, all patients discontinued their prior MTX without washout. The primary endpoints at Week (Wk) 14 were the proportion of patients who achieved ACR20, and the proportion who achieved DAS28-CRP ≤3.2 using non-responder imputation (NRI).

Results: All 648 randomized patients were treated; 92.3% completed 14 wks. BL demographics and disease characteristics were generally similar across arms. Primary and all key secondary endpoints were met (p<.001). At Wk14, significantly more patients on UPA15 and 30 vs cMTX achieved ACR20 (67.7% and 71.2% vs 41.2%), and DAS28-CRP≤3.2 (44.7% and 53.0% vs 19.4%). The proportion of patients achieving CDAI≤10 was significantly greater with UPA15 and 30 vs cMTX (34.6% and 46.5% vs 24.5%). Adverse events (AEs) were reported at similar frequencies across arms; serious AEs were numerically higher on UPA15 but similar between cMTX and UPA30. More infections were reported in cMTX and UPA30 vs UPA15. Herpes zoster was highest on UPA30. Three malignancies (cMTX: 1; UPA 15: 2), 3 adjudicated MACE (UPA15: 1; UPA30: 2), 1 adjudicated pulmonary embolism and 1 death (UPA15: stroke due to ruptured aneurysm) were reported. Laboratory abnormalities were consistent with prior UPA studies.

Conclusions: In this MTX-IR study population, switching to UPA as monotherapy at 15mg and 30mg QD showed significant improvements in RA signs and symptoms vs continuing MTX. Numerically higher responses were observed for UPA 30mg vs 15mg, particularly for more stringent efficacy criteria. Safety observations were similar to those in prior UPA studies.

227

LEVELS OF MYOKINES AND RADIOGRAPHIC PROGRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS

Jordana Miranda De Souza Silva^1,2, Rafaela Cavalheiro do Espírito Santo^1,2, Deborah Negrão Gonçalo Dias³, Nayara Felicidade Thomas Braz⁴, Érica Leandro Marciano Vieira⁴, Correa Eduarda Freitas^1,2, Ana Cristina Simões e Silva⁴, Rafael Mendonça da Silva Chakr^1,2, Adriana Maria Kakehasi⁴, and Ricardo Machado Xavier^1,2. ¹Laboratório de Doenças Autoimunes, Serviço de Reumatologia, Hospital De Clínicas De Porto Alegre, Porto Alegre, Brazil, ²Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, ³Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil, ⁴Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Objectives: Myokines are mainly expressed in the skeletal muscle, which is also their primary target tissue, and then released into circulation promoting crosstalk among different tissues. Considering that myokines, such as irisin and myostatin, have a role in bone tissue homeostasis, our aim was to investigate whether myokines serum levels can predict one-year radiographic progression in patients with rheumatoid arthritis (RA).

Methods: Forty female patients with RA, according to ACR/EULAR 2010 classification criteria, were included in the study. Thirty healthy subjects paired by sex, age and body mass index (BMI) were enrolled as the control group. Blood samples were collected, and ELISA was used to measure serum levels of irisin and myostatin. Radiographs of hands and feet, taken within three months of the blood collection and a year later, were evaluated using the Sharp-van der Heijde (SvH) score to verify the one-year radiographic progression in RA patients. The RA activity was assessed by disease activity score based on evaluation of 28 joints (DAS28-ESR). Statistical analysis included Mann-Whitney U test and Spearman correlation. A value of p<0.05 was considered significant.

Results: The mean age of the RA patients was 53 years, mean DAS28-ESR was 4.09, mean disease duration was 11.2 years and mean BMI was 27.33 kg/m2. The serum levels of irisin and myostatin were significantly lower in RA patients (25,61 ± 8,25; 3011,28 ± 1271,11) than in control subjects (30,36 ± 10,95; 4049,08 ± 1610,01). Considering radiographic progression, the mean values of SvH score were 28,3 and 31,3 in the first and in the second evaluation, respectively, resulting in a mean ΔSvH of 3. Over one year, 81,5% of the patients presented radiographic progression (ΔSvH score >0), and 21% presented rapid progression (ΔSvH score >5). Irisin and myostatin serum levels were not correlated with the radiographic progression.

Conclusions: The serum levels of irisin and myostatin were significantly lower in RA patients in comparison with control individuals and were not correlated with the radiographic progression. Irisin is known to retrieve disuse-induced bone loss by stimulating the osteoblast pathways, while myostatin was demonstrated to be highly expressed in the synovial tissues of RA subjects, with direct role in osteoclastogenesis. Based on our results, it is likely that the amount of irisin and myostatin that reaches the joint, or is produced in the joint environment, may differ from the circulating concentration.

231

RAPID RESPONSE WITH UPADACITINIB TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS AND AN INADEQUATE RESPONSE TO CSDMARDS OR BDMARDS

O. FitzGerald¹, A. Rubbert-Roth², K. Chen³, S. Meerwein⁴, J. Enejosa³, T. Shaw³, and A.F. Wells⁵. ¹St. Vincent’s Univ Hospital and Conway Inst Univ College Dublin, Dublin, Ireland, ²Kantonsspital St. Gallen, St Gallen, Switzerland, ³AbbVie, N Chicago, United States, ⁴AbbVie Deutschland, Ludwigshafen, Germany, ⁵Rheum and Immunotherapy Ctr, Franklin, United States.

Objectives: Upadacitinib (UPA), an oral JAK inhibitor selective for JAK1, demonstrated efficacy in patients with moderate to severe rheumatoid arthritis (RA) with an inadequate response (IR) to csDMARDs or bDMARDs in the SELECT-NEXT and SELECT-BEYOND trials, respectively. The purpose of the analysis was to investigate the speed of response to UPA across disease measures in csDMARD- and bDMARD-IR patients.

Methods: 661 patients in NEXT and 498 in BEYOND received UPA 15mg or UPA 30mg once daily (QD) or placebo (PBO) for 12 weeks (wks) (1,2). Time to first achievement of clinically meaningful outcomes, including ACR20/50, DAS28-CRP≤3.2 and Low Disease Activity (LDA) measures of CDAI (≤10) and SDAI (≤11) was evaluated. The cumulative incidences of ACR20/50, DAS28-CRP ≤3.2 and LDA by CDAI and SDAI over 12 wks were estimated. Hazard ratios between UPA and PBO were obtained using Cox proportional hazards model with treatment group, corresponding baseline values and main stratification factors, without control for multiple comparisons. All analyses were based on observed data without imputation.

Results: Patient disease duration was 7 and 13 years in NEXT and BEYOND, respectively (1,2). BEYOND patients were treatment-refractory as evidenced by 53% having received ≥2 prior bDMARDs. Median times to achieve ACR20 were 4 wks for UPA 15mg QD and 2-3 wks for UPA 30mg QD vs 12 wks on PBO (p<.001). Median times to achieve ACR50 and DAS28-CRP≤3.2 for UPA 15mg and 30mg QD were -12 wks and -8 wks for csDMARD-IR and bDMARD-IR patients vs PBO. Median time to LDA by CDAI and SDAI was -12 wks on UPA vs PBO. Patients receiving UPA were 2-4 times more likely to achieve clinical responses vs PBO. Quicker responses were observed in patients receiving UPA 30mg vs UPA 15mg QD. Median times to achieve 20% improvements in morning stiffness duration and severity were approximately 2 wks in each of the UPA arms vs 4 wks on PBO (p< 0.001).

Conclusions: Patients receiving UPA at either 15mg or 30mg QD were more likely to achieve clinical responses at significantly earlier time points when compared with patients receiving PBO. Irrespective of being csDMARD-IR or bDMARD-IR, times to achieve various clinical responses were consistent between pt populations.

232

PRESENCE OF COMORBIDITIES IN PARAGUAYAN PATIENTS WITH ESTABLISHED RHEUMATOID ARTHRITIS

Susan Riquelme-Granada¹, Rodrigo Acosta¹, Astrid Paats¹, Víctor Martínez¹, Lourdes Román¹, and Sonia Cabrera¹. ¹Hospital De Clínicas Paraguay, Asunción, Paraguay.

Objectives: To describe the clinical-epidemiological characteristics and the presence of comorbidities in Paraguayan patients with established RA.

Methods: Descriptive, analytical, cross-sectional study of a cohort of patients with established RA. We reviewed the clinical records of patients with regular follow-up and extracted clinical, epidemiological and laboratory variables for analysis. The qualitative variables were expressed in terms of frequencies and percentages, while the quantitative variables were expressed as means with their respective standard deviations. The statistical analysis was carried out with the SPSS V.23.0 program.

Results: We included 119 patients. 83.2% (99/119) were women, with a mean current age of 52.65 ± 12.97 years and average disease duration of 117.45 ± 95.53 months. Only 5.9% (7/119) were tobacco users. 31.9% (38/119) had extra-articular manifestations, 40.4% (42/104) had erosions and 93% (111/119) were seropositive. 79% (94/119) were being treated with methotrexate, 47.9% (57/119) with 2 or more DMARDs, 32.8% (39/119) with glucocorticoids, at an average dose of 4,6 ± 2.48 mg/d and 27.7% (33/119) with NSAIDs.

Concerning disease activity, 39.5% (47/119) were in remission. Average HAQ was 0.56 ± 0.37. 42.9% (51/119) were overweight and 30.3% (36/119) were obese. 39.5% (47/119) had hypertension, 10.1% (12/119) diabetes and 21% (25/119) dyslipidemia. Mean BMI was 30.42 ± 5.7, mean hip circumference was 104.86 ± 9.8 cm and mean abdominal circumference was 93.85 ± 11.79 cm. 59% (69/119) had a family history of hypertension and 18.8% (22/119) of diabetes.

Conclusions: In our cohort of Paraguayan patients with established RA, most of whom were overweight and obese, we had a high percentage of patients with arterial hypertension and family history of this comorbidity.

235

PREVALENCE OF ANXIETY/DEPRESSION IN PATIENTS WITH RHEUMATOID ARTHRITIS AT THE UNIVERSITY OF CHILE`S CLINICAL HOSPITAL AND THEIR ASSOCIATIONS WITH DIFFERENT DISEASE ACTIVITY INDICES AND QUALITY OF LIFE

Anne-Marie Chassin-Trubert Contreras¹, César Lillo Dubó¹, Stephanie Prieto Suazo¹, Héctor Gatica Rossi¹, Pilar Carrasco Cordero¹, Ariel Castro Lara¹, Francisca Sabugo Siraqyan¹, Pamela Wurmann Kiblisky¹, Francisca Bozán Pérez¹, Julio Cruz Carrasco¹, Silvana Saavedra Gutiérrez¹, and Annelise Goecke Sariego¹. ¹Hospital Clínico de la Universidad de Chile, Santiago, Chile.

Objectives: To evaluate the prevalence of anxiety/depression in rheumatoid arthritis patients being followed at the University of Chile`s Clinical Hospital and to investigate the association of anxiety/depression with disease activity and quality of life.

Methods: The Hospital Anxiety Depression Scale (HADS) was applied to measure depression and anxiety in a cross-sectional sample of patients with RA meeting the ACR/EULAR 2010 criteria being followed at the University of Chile`s Clinical Hospital. All patients included gave their inform consent. Demographic characteristics, disease variables and activity, measure as DAS28-ESR, DAS-28 CRP, CDAI and SDAI and HAQ were evaluated at the same time. Spearmen correlation, Fisher exact test, Chi-Square and Kruskal-Wallis test were used according to variables at evaluation. Statistical analysis was performed by Stata v12.1 sfotware. The study was approved by the Hospital Ethic Review board.

Results: 122 patients were enrolled in the study between December 2017 and December 2018. 103 (84.45%) were female. 56 (46%) had depression and/or anxiety according to HADS. 24 % of the patients (n=24) had only depression. The severity of the depression symptoms was mild 71%, moderate 21% and severe 8%. 42%, 40% and 18% of the patients with anxiety (n=55) had mild, moderate and severe anxiety symptoms, respectively. The disease activity was significantly higher in patients with anxiety/depression as compared to those withoutmeasured by the following indices: DAS28-VHS (4.33 vs 2.75, p<0.001), DAS-28 CRP (4.13 vs 2.75, p<0.001), CDAI (15 vs 7, p<0.001) and SDAI (17 vs 7.5, p<0.001). The HAQ was also significantly higher in patients with anxiety/depression (1.18 vs 0.29, p<0.01).

Conclusions: Depression/anxiety symptoms were very frequent in our cohort of RA patients. The disease activity measure with different indices and the HAQ were significantly higher in thosepatients with depression/anxiety. It is possible that psychological factors influence RA treatment outcomes. Therefore, screening and therapy of anxiety and depression should be considered in the regular management of RA patients.

236

TEMPOROMANDIBULAR DISORDERS IN PATIENTS WITH RHEUMATOID ARTHRITIS: A CLINICAL STUDY

Suleyman Ozbek¹. ¹CU Medical Faculty Balcali Hospital, Yüregir, Turkey, ²CU Medical Faculty, Adana, Turkey.

Objectives: The aim of this study is to evaluate the prevalence and type of temporomandibular disorders in patients with rheumatoid arthritis (RA).

Methods: 54 subjects having RA and receiving treatment at Cukurova University Rheumatology Clinic were enrolled into the study. Demographic and rheumatologic data were recorded. The subjects were examined in Dental Faculty using Research Diagnostic Criteria/Temporomandibular Disorders (RDC/TMD) Axis I and answered RDC/TMD Axis II Biobehavioral Questionnaire. Data from questionnaire was evaluated according to the instructions for scoring and assessment of RDC/TMD. Characteristic pain intensity (CPI), disability score (DS), depression items (DEP), nonspecific physical symptoms-pain items included (NPS-included), nonspecific physical symptoms-pain items excluded (NPS-excluded), chronic pain grade (CPG) were calculated and recorded. Statistical analysis was done with SPSS 15.0. Mann-Whitney test was used to compare continuous variables between two groups and Kruskall-Wallis test to compare continuous variables for more than 2 groups.

Results: Subjects (20.44% male, 79.6% female) were generally evaluated as categorical and continuous variables. Although their activity situation were 55.6% active and 44.4% inactive, the distribution of treatment modality was 31.5% for anti-TNF-α and 68.5% for DMARD. The distribution of TMJ involvement was; 9.3% with no involvement, 7.4% with joint involvement, 64.8% with muscular involvement, 18.5% with muscular+joint involvement. Subjects were categorized according to their rheumatologic functional scores and the scores were (0) 3.7%, (1) 50%, (2) 38.9%, (3)7.4%. Due to RDC/TMD Axis II scoring protocol, subjects’ chronic pain was graded from (0) to (4) and the distribution was 3.7%, 24.1%, 20.4%, 31.5% and 20.4%, respectively. Mean and standard deviation values of duration of RA, age, CPI, DS, DEP, NPS included, NPS excluded which were determined as continuous variables in this study were 8.50±6.28, 46.56±10.36, 53.85±27.60, 44.94±29.31, 1.57±1.87, 1.81±0.83, 1.74±0.84 respectively.

Conclusions: There was a high prevalence of TMD in RA patients. Muscular involvement was the most frequent type of TMJ involvement. Thus, early management should be applied to prevent the functional impairment of TMJ.

241

IMPACT OF PRIOR BIOLOGIC USE ON TREATMENT RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING ADALIMUMAB IN ROUTINE CLINICAL CARE: RESULTS FROM THE PASSION STUDY

F. Van den Bosch¹, S. Wassenberg², P. Zueger³, J. Kalabic⁴, M. Wu³, K. Monastiriakos³, and A. Östor⁵. ¹Ghent University Hospital, Ghent, Belgium, ²Rheumazentrum Ratingen, Ratingen, Germany, ³AbbVie Inc., North Chicago, United States, ⁴AbbVie Deutschland Co. GmbH, Ludwigshafen, Germany, ⁵Cabrini Medical Centre, Melbourne, Australia.

Objectives: It is recognized that early diagnosis and treatment are important in maximizing long-term quality of life in patients (pts) with rheumatoid arthritis (RA). Prior biologic disease modifying antirheumatic drug (bDMARD) use has been shown to affect treatment response to further biologic therapy including adalimumab (ADA).

Here we evaluate the impact of prior bDMARD use on clinical and pt-reported outcomes in pts enrolled in the PASSION study.

Methods: PASSION, a 78-wk postmarketing, multinational, observational study. Assessed the effectiveness of ADA in pts with moderate to severe RA receiving ADA in routine clinical care in the context of participation in the voluntary AbbVie pt support program. Pts with an insufficient response to ≥1 DMARD (1 prior bDMARD was allowed) and newly initiating ADA were enrolled and categorized as bDMARD-naïve or bDMARD-experienced. For the present analysis, ADA treatment response was determined by evaluating least squares (LS) mean change from baseline for multiple clinical and pt-reported outcomes. Missing data for each efficacy endpoint were imputed using last observation carried forward, and differences between groups for efficacy endpoints at wks 24, 52, and 78 were based on ANCOVA models adjusting for baseline and demographic variables. Additionally, the percentages of pts at each time point (observed population) who achieved HAQ-DI minimal clinically important difference (MCID; improvement from baseline of ≥0.22) were assessed.

Results: Of 1025 pts included in the intent-to-treat population, 182 were bDMARD-experienced and 843 were bDMARD-naïve at baseline. There were no significant differences between groups in sex, race, ethnicity, weight, height, body mass index, TJC28, SJC28, and pain at baseline. However, bDMARD-experienced pts were significantly older, had longer RA duration, and had lower values for HAQ-DI, DAS28(CRP), CDAI, SDAI, PtGA, and PhGA than bDMARD-naïve pts at baseline (P<0.05 for all). ADA treatment response was significantly higher for bDMARD-naïve vs bDMARD-experienced pts at all timepoints for HAQ-DI, DAS28(CRP), CDAI, PtGA, and pain, at wks 24 and 52 for SDAI, and at wk 24 for TJC28 and SJC28. In the observed population, a large percentage of bDMARD-naïve and bDMARD-experienced pts achieved HAQ-DI MCID at wk 24 (67% and 60%), wk 52 (71% and 65%), and wk 78 (74% and 59%).

Conclusions: Among pts with moderate to severe RA that initiated ADA treatment in the PASSION study, bDMARD-naïve pts achieved significantly larger improvements from baseline to wk 78 in a variety of clinical and pt-reported outcomes compared with bDMARD-experienced pts. A large proportion of both bDMARD-naïve and bDMARD-experienced pts achieved HAQ DI MCID with ADA treatment.

243

THE ASSOCIATION BETWEEN PATIENT REPORTED OUTCOMES AND CLINICAL MEASURES AMONG RHEUMATOID ARTHRITIS PATIENTS: ANALYSES USING PHASE 3 CLINICAL TRIALS OF UPADACITINIB

Vibeke Strand¹, Nemanja Damjanov², Craig Scoville³, Namita Tundia⁴, Heidi Camp⁴, Kun Chen⁴, Jessica L Suboticki⁴, and Ronald van Vollenhoven⁵. ¹Stanford University, Palo Alto, United States, ²Belgrade University School of Medicine, Belgrade, Serbia, ³Idaho Falls Arthritis Clinic, Idaho Falls, United States, ⁴AbbVie Inc., N Chicago, USA, ⁵Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, Netherlands.

Objectives: Patient-reported outcomes (PROs) in RA are important to evaluate total disease impact, although treatment decisions may often be guided by traditional physician-derived measures of disease activity. The purpose of this analysis was to determine the association between PROs and composite outcomes in RA patients receiving the JAK1-selective inhibitor, upadacitinib (UPA), with prior inadequate responses (IR) to conventional synthetic (cs) or biologic (b) DMARD(s).

Methods: Data were analyzed from two 12-week (wk), phase 3, RCTs in csDMARD-IR (SELECT-NEXT) and bDMARD-IR (SELECT-BEYOND) patients receiving UPA 15 or 30 mg daily (QD) or placebo and background csDMARD therapy; as well as from a third trial (SELECT-MONOTHERAPY), in which MTX-IR patients received UPA monotherapy or MTX (blinded) for 14 wks. Moderate and substantial improvements in pain (≥30% and ≥50% improvement from baseline [Δ BL], respectively), and normative values in HAQ-DI (≤0.25) and functional assessment of chronic illness therapy-fatigue (FACIT-F: ≥43.6, SELECT-NEXT only) were evaluated. Associations between clinical outcomes (TJC, SJC, physician global assessment [MDGA], CRP and composite measures [ACR, DAS28-CRP, CDAI]), and PROs (pain [VAS], HAQ-DI, patient global assessment [PtGA], morning stiffness, FACIT-F) were evaluated through Pearson correlations and a univariate logistic model, controlling for treatment group and BL value.

Results: Patients enrolled in the SELECT-NEXT and SELECT-BEYOND trials had moderate to severely active RA (mean DAS28-CRP: 5.6 and 5.8, respectively), with disease durations of 7 and 12 years, respectively. In general, ΔBL in pain and HAQ-DI scores were marginally correlated with individual physician-derived measures (SELECT-NEXT: pain, 0.161-0.537, HAQ-DI, 0.081-0.425; SELECT-BEYOND: pain, 0.131-0.511, HAQ-DI, 0.052-0.409); moreover, moderate to high correlations were observed between pain, HAQ-DI and PtGA in both RCTs (SELECT-NEXT: pain, 0.835-0.851, HAQ-DI, 0.418-0.518; SELECT-BEYOND: pain, 0.828-0.871, HAQ-DI, 0.479-0.520). In regression analyses, improvements in individual disease assessments were associated with significant improvements in pain at Wk12 across RCTs. In addition, patients with improvement in composite measures were more likely to report substantial improvements in pain. Similar associations were evident for HAQ-DI scores at Wk12 across RCTs (including SELECT-MONOTHERAPY), as well as for FACIT-F in SELECT-NEXT.

Conclusions: Achieving substantial improvements in pain, physical function, and fatigue was associated both with individual physician-derived measures and with composite disease outcomes. These data support the use of PROs in RCTs and also imply that, although PROs may be included in composite endpoints, they are distinct parameters that provide additional insights into the true impact of RA.

258

EVALUATION OF CITRULLINATED ANTI-VIMENTIN ANTIBODIES, ANTI-CITRULLINATED CYCLIC PEPTIDE ANTIBODIES IN ECUADORIAN PATIENTS WITH RHEUMATOID ARTHRITIS

Camilo Zurita-Salinas⁴, Cristina Aguilera-León¹, Marilú Mestanza-Peralta², Alejandro Zurita-Mestanza³, and Simón Meneses¹. ¹Zurita & Zurita Laboratorios, Quito, Ecuador, ²Hospital Metropolitano, Quito, Ecuador, ³Universidad San Francisco de Quito, Quito, Ecuador, ⁴Universidad Central del Ecuador, Quito, Ecuador.

Objectives: Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease that affects about 1% of the Ecuadorian population. The diagnosis of the disease is based on clinical manifestations, as well as on routine serological tests used for the determination of autoantibodies in patients with RA. Rheumatoid factor (RF) has been well described and is present in 70% in patients with RA. The objective of the present study is to evaluate some antibodies such as citrullinated mutated antivimentin antibodies (anti-MCV), anti-citrullinated cyclic peptide (anti-CCP) and IgM rheumatoid factor in a cohort of Ecuadorian patients with rheumatoid arthritis.

Methods: This is an initial descriptive study that will compare HLA, disease activity and disease duration in RA patients from Quito-Ecuador; there were 39 RA patients in whom quantitative ELISA was performed (Anti-MCV ®, ORGENTEC Diagnostika GmbH, Germany, Diamedix ™ Immunosimplicity ™ ELISA Kit, ARCHITECT Anti-CCP, Architect system) to determine serum antibodies and rheumatoid factor.

Results: Anti-MCV antibodies, anti-CCP and rheumatoid factor showed 66.67%, 66.67% and 64.10% positivity in the RA patientsrespectively. The average MCV titers were 281.255 U / mL, in this study, the anti-MCV antibodies had sensitivity and diagnostic specificity of 96.30% and 76.46% (versus anti-CCP), positive predictive value of 86.67% and negative of 92.86%. The anti-CCP antibodies showed a specificity of 92.86% and sensitivity of 86.67% (versus anti-MCV), positive predictive value of 96.30%, negative predictive value of 76.47%, while the rheumatoid factor presented sensitivity and specificity of 84.00% and 79.57% (versus anti-CCP), positive predictive value of 87.50% and negative of 73.33%.

Conclusions: According to the results of this study, not only the determination of anti-MCV but also of anti-CCP and rheumatoid factor assist in the diagnosis of RA and may be beneficial for the estimation of other parameters in patients with rheumatic diseases.

260

PATIENT SATISFACTION AND ACCEPTABILITY OF ULTRASOUND IN THE EVALUATION OF RHEUMATOID ARTHRITIS

Jaime Mendoza Torres¹, Luis Rodriguez¹, Hector García¹, Dennise Clavijo¹, Chiara Bertolazzi¹, Mario Morales², Antonio García², Carlos Pineda¹, and Marwin Gutierrez¹. ¹Instituto Nacional de Rehabilitación Dr. Luis Guillermo Ibarra Ibarra, Ciudad de México, México, ²Hospital Nacional Arzobispo Loayza, Lima, Perú.

Objectives: To determine the level of patient´s satisfaction and acceptability of ultrasound (US) as a tool for the assessment of rheumatoid arthritis (RA).

Methods: We included patients ≥18 years with diagnosis of RA (ACR/EULAR 2010 criteria) referred to our Division, by a rheumatologist, for an US examination.

After the US examination, a questionnaire aimed at evaluating the level of satisfaction was administered to all patients. It included 5-items rating with their level of agreement according to Likert scale: A. I received a clear explanation about the usefulness of US in RA. D. I received a clear explanation of the importance of US results. C. To see the images that were taken during my US examination helped me to better understand my disease. D. In the future, I would like to repeat the US examination for monitoring my disease. E. I believe that US examination will provide useful information to my rheumatologist for my treatment.

Additionally, five additional queries testing comfort, acceptability and usefullness of US in their disease were included.

Results: A total of 90 patients (mean age ± SD, 53.4 ± 12.2 years; 85 [94,4%] female) were included. Mean disease duration was 10.6 ±7.1 years. Overall score of satisfaction for the 5 items was 4.8 (range 3–5). Item A, D and E reached a 100% of agreement whereas item B and C obtained 98.9% and 93.3% of agreement, respectively. All patients agreed to repeat the US examination since US improved the understanding of their medical condition. Additionally, there was a 94% agreement that the US could help the rheumatologist to make decisions regarding the treatment of their RA.

Conclusions: Our preliminary results demonstrated that RA patients have a good perception of the US for the assessment of their disease. In particular, they expressed satisfaction and good acceptability.

261

EFFECTIVENESS OF BIOLOGICAL DMARD THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER A T2T STRATEGY. A REAL WORLD- DESCRIPTIVE STUDY

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab - Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES - Investigación y Educación en Salud, Bogotá, Colombia.

Objectives: Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease which affects joints and has systemic effects. Biological DMARDs have demonstrated to modify the natural course of the disease through the inhibition of specific molecules of the immune and inflammatory responses. The aim of this study was to evaluate the disease activity response to Biological DMARDs in Colombian patients with RA.

Methods: We carried out a medical record review real-life study from 2015 to 2018. Patients were followed-up under T2T standards and a multidisciplinary approach. Clinical follow-up was performed according to DAS28. We divided patients in four groups: remission (REM), low disease activity (LDA), moderate disease activity (MDA) and severe disease activity (SDA) patients; the aim was to observe the percentage of patients who were in moderate or severe disease activity and reached a low disease activity or remission. Descriptive epidemiology was done, we calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. We analyzed normality for DAS 28, in order to compare disease activity and the end of follow-up.

Results: For 3 years we included 1054 patients, 85% were female, mean age was 57 years SD 7.7. At beginning 52% of patients were in MDA and 48% in SDA. The most used treatment regime was certolizumab 24.5% followed by etanercept 16.5% and abatacept 12.8%. At the beginning 52% of patients were in MDA and 48% in SDA; at the end of the follow up 92% patients achieved remission. We performed a Wilcoxon test in order to compare the median DAS28 at baseline and at the end showing statistical significance (p< 0.05). In general, all biologics used had equivalent effectiveness.

Conclusions: Therapy with biological DMARDS are effective when used under a T2T strategy and a multidisciplinary approach. All of the biological regimes achieved the target for the treatment of RA – a remission or low disease activity. Our findings are similar to those of other studies where biological DMARDs are an effective option for treating patients with RA in a real-life setting (1). However, other considerations such as costs and patient´s context should be taking into account to prescribe biological therapy.

262

REAL WORLD CONVENTIONAL DMARDs RESPONSE IN PATIENTS WITH RHEUMATOID ARTHRTIS: 3-YEAR RESULTS FROM AN OBSERVATIONAL STUDY

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab - Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES - Investigación y Educación en Salud, Bogotá, Colombia.

Objectives: Rheumatoid arthritis (RA) is a common autoimmune disorder that affects 40 per 100,000 persons. Current recommendations aim to achieve remission or low disease activity. Regarding pharmacological therapy, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have demonstrated to be effective for treating RA they slow the damage to joints and, sustain disease control. We aimed to describe csDMARDs disease activity response and usage in a specialized rheumatoid center in Colombia.

Methods: We carried out a medical record review real-life study from 2015 to 2018. Patients were followed-up under T2T standards and a multidisciplinary approach. Clinical follow-up was performed according to DAS28. We divided patients in four groups: remission (REM), low disease activity (LDA), moderate disease activity (MDA) and severe disease activity (SDA) patients; we observed the percentage of patients who were in moderate or severe disease activity and reached a low disease activity or remission. Descriptive epidemiology was done, we calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. We analyzed normality for DAS 28, in order to compare disease activity and the end of follow-up.

Results: For 3 years we included 2653 patients who were receiving conventional DMARDs, mean age was 58.1 SD 13.6, most of patients were female, 84%. Regarding disease activity 71% were in MDA and 29% in SDA. The most used conventional DMARD methotrexate, 23% followed by leflunomide, 21%. At the beginning 79% of patients were in MDA and 21% in SDA. At the end of the follow-up period 86% achieved remission and 6% achieved LDA. We performed a Wilcoxon test in order to compare the mean DAS28 at baseline and at the end showing statistical significance (p<0.05). The most effective cDMARDs were metothrexate and leflunomide.

Conclusions: This descriptive study represents a real-life cohort of patients who achieved remission with the use of conventional DMARDs. Thus, it supports the evidence that a conventional DMARD therapy and under a T2T model achieve favorable results in regarding disease activity.

265

TREAT TO TARGET MULTIAPPROACH MODEL IN A 3 YEAR FOLLOW-UP COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS. REAL-LIFE EFFECTIVENESS

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab - Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES - Investigación y Educación en Salud, Bogotá, Colombia.

Objectives: The goal in rheumatoid arthritis (RA) treatment is to achieve remission. The treat-to-target recommendations, formulated in 2010, have provided a foundation for the implementation of a strategic approach in order to achieve remission in routine clinical practice. The objective of this research was to describe global change in Disease Activity Score 28 (DAS28) using T2T strategy and a multidisciplinary model of care for a 3-year period in patients with RA who receive conventional or biological DMARD and were cared for at a specialized center in Colombia.

Methods: A descriptive cohort study was conducted. Medical records of patients from a specialized RA center were reviewed between 2015 and 2018; those patients were followed-up under T2T standards and a multidisciplinary approach. Each patient had a minimum of 6 follow-up visits. Clinical follow-up was designed by the authors according to DAS28. Therapy had to be adjusted with DAS28 > 3.2 unless patient´s conditions did not permit it; we considered this follow-up type as implementation of a T2T strategy in patients with RA. The aim was to observe the percentage of patients who were in moderate or severe disease activity and reached low disease activity or remission. Descriptive epidemiology was done, we calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. We analyzed normality for DAS28, in order to compare disease activity at beginning and the end of follow-up.

Results: For 3 years we included 3699 patients, 72% were receiving conventional DMARDs and 18% biologics. 84% were female, mean age was 58 years with SD 13.02. At the beginning, the median DAS28 was 4.63 IQR (3.95-5.45), while at the end of follow up was 1 IQR (1-2). At the beginning 66% of patients were in MDA and 34% of them in SDA. When we measured DAS28 at 3-year follow-up 88% of our patients achieved remission and another 5% achieved LDA. In our study, DAS28 was not normally distributed, thus we performed a Wilcoxon test in order to compare the mean DAS28 at baseline/3-year follow-up showing statistical significance (p<0.05).

Conclusions: The implementation of a T2T protocol in patients with RA is effective to achieve remission; on the other hand, a T2T multidisciplinary team is an additional component that helps to achieve LDA or remission. These findings show as in other studies that T2T strategies achieve better results compared to conventional care.

266

PERIPHERAL NEUROPATHY MANIFESTATIONS IN RHEUMATOID ARTHRITIS PATIENTS AND ITS ASSOCIATION WITH SERUM VITAMIN B 12 LEVELS

Franz Diego Zevallos Zúñiga¹, Carlos Huanqui¹, and Jenny Yafac¹. ¹Hospital Regional Honorio Delgado, Arequipa, Perú.

Objectives: To determine peripheral neuropathy manifestations in rheumatoid arthritis patients and their association with serum Vitamin B 12 levels.

Methods: 50 clinically diagnosed Rheumatoid Arthritis (RA) patients were included in this study. We have excluded patients with systemic illnesses or with other conditions causing peripheral neuropathy. For the determination of peripheral neuropathy, a complete history, clinical examination, electrophysiology nerve conduction studies were done. The dosage of serum Vitamin B12 levels were done through spectrophotometry. We use DAS28-ESR to estimate RA activity of in our patients. For the statistical analysis, the Student’s T-test for comparison between the two groups (with and without neuropathy) and Spearman’s correlation for continuous variables were used. For the relationship between peripheral neuropathy and disease activity, the Chi square test was used.

Results: A total de 50 RA patients (49 females and 1 male) were enrolled in this study. The patients studied had mild or moderate disease activity. Peripheral neuropathy was found in 31 patients (62%). Of these, the diagnosis was electrophysiological in 23(46%). 8 patients had clinical neuropathy without electrophysiological abnormalities. The types of neuropathy most frequently found, by electrophysiology nerve conduction study, were carpal tunnel syndrome in 13 patients, mononeuropathy in 7 patients and sensory-motor polyneuropathy in 4 patients. 44% have values higher than 720 pg/ml of vitamin B12 and 16% lower than 200 (Normal Value: >220 pg/ml). There was a statistically significant correlation between peripheral neuropathy and lower Serum vitamin B12 levels (p=0.02). Additionally, we found statistically significant correlation between peripheral neuropathy and activity of disease.

Conclusions: We found peripheral neuropathy in 46 % of RA patients and in 16 % of them vitamin B12 deficiency was present. This vitamin deficiency is one of the participant etiologic factors in the generation of peripheral neuropathy.

276

CHARACTERISTICS OF PATIENTS CARED FOR AT AN INFUSION THERAPY FACILITY IN AN OUT-PATIENT RHEUMATOLOGY CENTER IN BOGOTÁ, COLOMBIA

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab, Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES, Investigación y educación en salud, Bogotá, Colombia.

Objectives: Rheumatoid arthritis (RA) is a common inflammatory condition that affects around 1% of the world population. The goal of administiering pharmacological therapy is to achieve remission or low disease activity in order to relieve pain, stiffness and other symptoms related to the condition. Some patients treated with disease-modifying antirheumatic drugs (DMARDs) are required to be administered under well established protocols, procedures, and practices in an infusion center setting. The aim of our research was to describe the characteristics of patients with rheumatoid arthritis who receive their care at an infusion therapy facility in an outpatient setting in Colombia.

Methods: We performed a descriptive study during 2018. We reviewed the medical records of the infusion therapy facility and extracted information related to sex, age and treatment. Descriptive epidemiology was performed for each variable.

Results: We reviewed 1131 medical records of patients who were cared for at our infusion therapy facilty during 2018. 82% were female, mean age was 56-years, SD 12. From the total of patients, 61% received a sub cutaneous DMARD followed by an intravenous DMARD, 39%. Regarding the pharmacological therapy 78% were receiving biological DMARDs, the most prescribed biological DMARD was Certolizumab in 19%, followed by tocilizumab in 13.35% and abatacept in 10.52%. Methotrexate was the only conventional DMARD administered in the infusion facility.

Conclusions: Biologic agents are the most common medications administered in our infusion facilty. Biological therapy has been associated with high costs for health systems, thus it is important to evaluate the financial implications of the usage of biological therapy in patients with RA and the costs that are brought in to an infusion facility for the administration of anti- rheumatic DMARDs; additionally further research is needed in order to evaluate the patient’s satisfaction regarding their pharmacological therapy and the implications for being care for at an infusion therapy facility, periodically.

279

COMORBIDITIES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab - Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES - Investigación y Educación en Salud, Bogotá, Colombia.

Objectives: Rheumatoid arthritis (RA) is systemic autoimmune disease characterized by joint inflammation and deformities. Patients with RA are also reported to have a high prevalence of comorbidities such as cardiovascular disease, diabetes and osteoporosis, among others. The presence of comorbidities might have an impact on patient’s treatment, resulting in less optimal outcomes. Currently, little is known about comorbidities in RA patients in Colombia. Our aim is to provide data from a real-life setting regarding comorbidities in RA patients.

Methods: We reviewed the medical records from RApatients being care for at our specialized center during 2018 and had a diagnosis of RA. We collected sociodemographic information, and comorbidities regarding high blood pressure, diabetes mellitus, stroke, hearth failure, cardiac arrythmias, osteoporosis, renal chronic disease and Sjögren’s syndrome. We evaluated normality for continuous variables and categorical variables were presented as rates.

Results: A total of 3118 medical records were reviewed, the mean age of patients was 58 years ±13.02, 85% were women and 15% were men. Regarding pharmacological therapy 73% of patients were treated with conventional DMARDs and 27% with biological DMARDs. In our study, 26% of patients had one comorbidity and 8% two comorbidities. The most frequent was high blood pressure with 31%, followed by osteoporosis in 19%, and myocardial infarction in 20.37%, among others.

Conclusions: Our study presents data from a Colombian RA registry. This study showed a higher prevalence of comorbidities in RA patients compared to other studies. Advanced age could be related to these comorbidities. According to these results there is a clear need to implement multidisciplinary care teams that take into account the complexity of the management of patients with RA. Additionally, further research is needed in order to identify risk factors associated with comorbidities in patients with RA.

282

EFFECT OF ANTI-TNF THERAPY IN SECONDARY KIDNEY AMYLOIDOSIS IN A PATIENT WITH REFRACTORY RHEUMATOID ARTHRITIS: CASE REPORT

Adriana Berez¹, Viviana Dominguez², and Fernanda Athaydes³. ¹Asociación Española, Montevideo, Uruguay, ²Asociacion Española, Montevideo, Uruguay, ³Asociacion Española, Montevideo, Uruguay.

Objectives: Rheumatoid arthritis (RA) could cause several complications; Secondary Amyloidosis (SAm) occur with a low frequency but it is asevere one. The most common clinical presentation includes renal involvement with functional failure and/or proteinuria.

There is no specific treatment for SAm and its course is usually refractory to RA treatment. Disease-modifying anti-rheumatic drugs (DMARDs) are associated with potential risks including nephrotoxicity. Efficacy of biological therapies in RA has been demonstrated and is well known, but the benefit of inhibitors of tumor necrosis factor alpha (ANTI-TNF) in SAmis still not clear.

To report a clinical case of a patient with RA and AmS treated with ANTI-TNF α agent.

Methods: A 51-year-old woman, with hypothyroidism, severe RA from age 18 with intense inflammatory joint activity from the beginning. Rheumatoid factor and anti-citrullinated peptide antibodies were negative. Multiple treatments were indicated.

In addition, the patient required bilateral hip arthroplasties and surgical repair of ruptured tendons in both hands. Inflammatory activity parameters have been positive over the last 3 years: ESR, CRP, DAS 28.

She received prednisone, methotrexate and hydroxychloroquine. During 2016 the patient presented nephrotic syndrome with Proteinuria 24hs 5.7 g/l, Renal ultrasound was normal.

Renal biopsy confirmed the presemce of a renal Amyloidosis with compromise of glomeruli, interstitium and vessels. Congo red deposits were positive and birefringence under a polarized light microscope.

Immunosuppressive therapy was modified by increasing prednisone, maintaining methotrexate and hydroxychloroquine and associating enalapril.

In the absence of response and the persistently high proteinuria we resolved to start biological therapy.

Results: The TNF alpha inhibitor etanercept was selected using 50mg subcutaneously weekly. It was requested to the National Resources Fund (governing body for the use of high-cost therapies at the national level) which authorized the indication. The patient currently maintains this treatment

Follow-up at 24 months showed a clear decrease in proteinuria, with improvement of inflammatory parameters as well as DAS-28 measurement.

The patient did not present adverse reactions at the beginning of the treatment except for intercurrent urinary tract infections that led us to temporally discontinuation of some doses.

Conclusions: We describe the case of a patient with severe RA who developed secondary renal amyloidosis. She was treated with an ANTI-TNF agent with favorable clinical and analytical evolution at 24 months. Close follow-up on efficacy and safety of this treatment in our patient will be performed overthe ensuin years

291

THE EXPERIENCE OF A MULTIDISCIPLINARY TEAM MEETING ON PATIENT ASSESMENT AND MANAGEMENT IN A RHEUMATOID ARTHTITIS SETTING

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab, Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES, Investigación y educación en salud, Bogotá, Colombia.

Objectives: Rheumatoid arthritis (RA) is an inflammatory disease with a prevalence of 0.2 to 1%. Currently, the resolution of symptoms and avoidance of disabilities are accomplished in a small proportion of these patients. Nowadays, patients require follow up where a multidisciplinary team care programs are a good option. This approach considers not only the disease activity but psychosocial, adherence and other aspects. Conducting regular multidisciplinary team (MDT) meetings requires significant investment of time and finances. It is thus important to assessnthe benefits of such practice. Our aim is to evaluate the impact of MDT meetings for patients with complex RA.

Methods: Once a rheumatologist identified a patient with RA with indication to begin biological therapy, switching from one biological to another or with difficult diagnosis, a checklist is applied with an assessment of the patient’s condition. After this step, the patient is presented in a multidisciplinary team meeting where a rheumatologist, a pharmaceutical chemist, a psychologist, a physiatrist and a nurse assessed the particular case of the patient. Additionally, an ultrasound is performed in every patient in order to evaluate disease activity. Based on the patient´s disease activity, adherence to treatment, psychosocial and economic factors the pharmacological therapy and management of the patient is evaluated and adjusted if needed.

Results: For 12 months, 1473 patients were evaluated by our multidisciplinary team, 90% to define the pharmacological therapy, 10% for biologic switching and 7% for difficult diagnosis. Mean DAS28 of patients was 3.7 ± 1.37; once the multidisciplinary team discussed the patient’s conditions, context and other variables that could influence the disease, the following decisions were made; the team decided to continue follow up in 65% of patients; switching among biologicals was made in 11% of patients. Additionally, we found that the ultrasound is a great strategy to evaluate disease activity and to support the final plan to be followed with the patient.

Conclusions: As other studies have shown, a multidisciplinary evaluation and discussion of patient’s conditions specifically in RA can bring into discussion different viewpoints from different health care disciplines and perspectives. Additionally, this type of approach can avoid prescribing expensive therapies for the management of RA. With this strategy we not only contribute to the health outcomes of patients but to the Colombian health system.

292

ANALGESIC PRESCRIPTION FOR THE MANAGEMENT OF RHEUMATOID ARTHRITIS

Pedro Santos-Moreno¹, Laura Villarreal-Peralta¹, Michael Cabrera¹, and Diana Buitrago-Garcia². ¹Biomab - Centro de Artritis Reumatoide, Bogotá, Colombia, ²SIIES - Investigación y Educación en Salud, Bogotá, Colombia.

Objectives: Recent advances in pharmacological therapy for rheumatoid arthritis (RA) have resulted in joint inflammation becoming a more treatable cause of pain. Nonetheless, the prognosis for pain is still often unfavorable. Pain has been associated with fatigue and psychological distress. In many cases as part of the pharmacological therapy, RA treatment includes pain control medications. Our objective was to evaluate the characteristics and prescription patterns of pain control medications in a RA Center in Bogotá Colombia.

Methods: We collected data from the medical records in a specialized RA center during 2018; we collected sociodemographic information, DAS28, and the prescription of analgesic medications divided in three groups non-opioid analgesics, opioid analgesics and NSAIDS. We calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. We evaluated the relationship between disease activity and type of analgesic treatment.

Results: We included data from 3699 patients. 82% were women and 16% were men. Mean age was 58 years, SD 13.02. From all patients, 40% did not receive any pain medication. Between medications: Non-opioids were 41%, Opioids 16% and NSAIDs 3%. The most prescribed pain medication was paracetamol or dipyrone, followed by opioids. When we explored the relationship between disease activity and the usage of pain medications it was not statistically significant.

Conclusions: RA is a pain-associated condition; the most prescribed pain medication was paracetamol followed by opioids. Our results are similar to those of other studies. Further research is needed in order to identify variables that influence the prescription of pain medications for RA. The implementation of a T2T protocol in patients with RA is effective not only to achieve remission, but additionally to reduce the percentage of patients using analgesics.

295

COMPARISON OF CLINICAL PRESENTATION OF RHEUMATOID ARTHRITIS AMONG AN INDIGENOUS POPULATION OF SOUTHEASTERN MEXICO WITH A NON-INDIGENOUS POPULATION OF NORTHEASTERN MEXICO

Cesar Vidal Elizondo Solis¹, Mario Alberto Garza Elizondo¹, Ana Sofia Leal Bramasco¹, Jorge Alberto Esquivel Valerio¹, Dionicio Angel Galarza Delgado¹, David Vega Morales¹, Cesar Eduardo Luna Gurrola¹, Ingris Pelaez Ballestas², Brenda Roxanna Vazquez Fuentes¹, and Ivan De la Peña Thevener¹. ¹Servicio De Reumatologia E Inmunologia Clinica, Departamento De Medicina Interna, Monterrey, México, ²Departamento de Reumatologia, Hosiptal General de Mexico "Dr. Eduardo Liceaga", Ciudad de México, México.

Objectives: To compare the clinical characteristics of the disease in two different populations.

Methods: Observational, cross-sectional and historical study. Clinical records of patients with rheumatoid arthritis (RA) diagnosed according to the classification criteria proposed by the ACR/EULAR 2010 that received their medical care at the Fundación Esquipulas, San Cristóbal de las Casas, Chiapas or at the Hospital Universitario "Dr. José Eleuterio González" Monterrey, Nuevo León, during the period from 2017 to 2018 were reviewed. The variables collected were demographic data (gender, age, origin), clinimetric data (weight, height, BMI, number of tender joints, number of swollen joints, Visual Analogous Scales of pain), serology (erythrocyte sedimentation rate, C-reactive protein, Rheumatoid Factor (RF) isotypes IgM, IgG and IgA, anti-cyclic citrullinated peptic antibodies(CCPA), and anti-carbamylated proteins (anti-CarP) antibodies (IgM, IgG and IgA isotypes).A p <0.05 was considered statistically significant.

Results: A total of 97 evaluated patients were divided into two groups according to their origin. We assessed 51 nonindigenous patients and 46 Indigenous patients. The demographic characteristics are observed in Table 1. Approximately 93% were female. We observed statistically significant difference in age (51 vs 44 p<0.05), BMI (28.3 vs 24.89 p<0.05), cigarette smoking (41 vs 4.2 p<0.001), RF-IgA (58.8% vs 80.4% p<0.05), RF-IgG (13.7 vs32.6%% p<0.05), RF-IgM (66.7% vs 89.1% p<0.05), Anti-CarP-IgG (37.3% vs 60.9% p<0.05), and Anti-CarP-IgM (45.1% vs 10.9% p<0.05), Table 2.

Conclusions: The indigenous population presented an early onset of the disease with greater joint involvement than the non-indigenous population and higher prevalence of the three isotypes of Rheumatoid Factor. There is a need for more studies in this subject.

299

SCLERITIS AND TOFACITINIB

Hugo Javier Madariaga Charaja¹, and Valery Ascuña¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To report a case of nodular anterior scleritis in a patient with Rheumatoid Arthritis (RA) under treatment with tofacitinib.

Methods: case report

Results: A 65-year-old woman with a diagnosis of RA for 5 years, on treatment with methotrexate 25 mg SC weekly, leflunomide 25 mg/d, sulfazalacin 2.5 gr/d and deflazacort 3 mg/d on no remission (DAS -28: 2.9-4.1). Therefore, treatment with tofacitinib 5 mg c/12 h monotherapy was initiated, achieving remission after three months of treatment (DAS-28: 2.2). One year later the patient presented with photophobia and a right painful and red eye. Diagnosed by ophthalmologist as nodular anterior scleritis. Treatment was given with deflazacort 30 mg/day, which lead to the disappearance of scleritis.

Conclusions: Scleritis is a complication of RA, an ocular manifestation of rheumatoid vasculitis. Although tofacitinib has been shown to be effective in the treatment of RA, it seems to be ineffective in the treatment of this extra-articular complication.

We do not consider this manifestation to be an adverse event of Tofacitinib.

300

ULTRASOUND AS A USEFUL TOOL IN THE DIAGNOSIS OF RHEUMATOID ARTHRITIS IN PATIENTS WITH UNDIFFERENTIATED ARTHRITIS

Marwin Gutierrez^1,2, Chiara Bertolazzi^1,2, Edwin Castillo³, Samuel Reyes-Long¹, Luis Rodriguez¹, Jaime Mendoza¹, Denise Clavijo-Cornejo^1,2, Carlos Pineda¹, and Pedro Santos-Moreno³. ¹Division of Musculoskeletal and Rheumatic Disorders. Instituto Nacional de Rehabilitacion, Mexico City, México, ²Rheumatology section, Clinic of Excellence in Rheumatology, Mexico City, México, ³Center of Rheumatoid Arthritis, BIOMAB, Bogotá, Colombia.

Objectives: Nowadays, rheumatologists face challenges in finding an effective method to classify and treat patients with undifferentiated arthritis (UA). There is a need for new tools that could ensure accurate characterization of inflammatory processes in these patients.

Methods: We conducted a cross sectional study in two rheumatology care clinics. Patients not fulfilling the 2010 ACR/EULAR RA criteria were included. On the examination day, all patients underwent a physical examination, radiographs and US. The 7-joint US score (US 7) was adopted to scan all patients. US was performed according to EULAR criteria and interpreted by OMERACT definitions. Greyscale and power Doppler synovitis and tenosynovitis were scored. Bone erosions were also evaluated during the US examination.

Results: A total of 204 patients were included. The diagnosis was modified from UA to RA in 86 (42.1%) patients. Also, the final score of the 2010 ACR/EULAR RA classification criteria changed from a mean of 4.6 to 6.5 after the US examination. In addition to synovitis, a wide range of tenosynovitis and bone erosions were detected by US. Synovitis was more frequently detected in the 2ndMCPj followed by the 2ndMTPj and the 5thMTPj. The tendons of the wrist, 2nd and 3th finger were the most frequently affected. In relation to bone erosions, the 2ndMCPj and 5thMTPj where the joints with more proportion of anatomical damage.

Conclusions: US demonstrated to be useful to help accurately classify as RA inpatients previously diagnosed with UA.

303

ETANERCEPT AND OCULAR DISEASE IN PATIENTS WITH INFLAMMATORY DISEASES

Hugo Javier Madariaga Charaja¹, Valery Ascuña¹, and Maria Elena Luza¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To report two patients with ocular disease secondary to juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) under treatment with etanercept.

Methods: case report

Results: Case 1: 7-year-old male, with diagnosis of JIA type polyarticular rheumatoid factor (RF) positive. On treatment with Etanercept 25 mg SC weekly associated with methotrexate 10 mg weekly, two years later, visual acuity decreased in both eyes (BE), predominantly, the right eye (RE). Ophthalmological evaluation revealed bilateral panuveitis. Etanercept was discontinued. Treatment with methylprednisolone, oral prednisone and methotrexate 22.5 mg SC weekly were given. Improvement in visual acuity with decreased ocular inflammation followed. Awaiting initiation of therapy with adalimumab.

Case 2: 57-year-old woman with diagnosis of RA on treatment with Etanercept 50 mg SC weekly, associated with methotrexate 10 mg weekly. Three months later, she presented a painful and red left eye; pain increased with eye movements/ Diagnosed by ophthalmology as diffuse anterior scleritis. 50 mg of prednisone was indicated daily, Etanercept was discontinued and methotrexate was increased to 22.5 mg weekly; due to poor response, treatment with cyclophosphamide 1 g IV was started.

Conclusions: - Uveitis is a very rare complication of the polyarticular presentation of JIA (0.1-1%); it is usually recurrent unilateral anterior uveitis. In the reported patient, it presented as bilateral panuveitis. Probably, as noted in other case reports, it is an adverse effect to Etanercept.

- Scleritis is a complication of RA (rheumatoid vasculitis). Etanercept, despite being effective for the control of joint disease, is not effective in controlling rheumatoid vasculitis. We do not consider it an adverse event of Etanercept.

305

EVALUATION OF THE AGREEMENT OF THE HAQ PERUVIAN VERSION IN PATIENTS WITH RHEUMATOID ARTHRITIS USERS OF BIOLOGICAL THERAPY

Wilkerson Perez Medina¹, and Cynthia Olarte Soto². ¹Hospital Edgardo Rebagliati Martins, Lima, Perú, ²University Nacional Mayor de San Marcos, Lima, Perú.

Objectives: To evaluate the agreement of the Peruvian version of the HAQ (Health Assesment Questionnaire) in a cohort of rheumatoid arthritis (RA) patients, users of biological therapy.

Methods: We evaluated RA patients, biological therapy users, who scored the HAQ twice with a difference of 7 to 10 days, absolving doubts if necessary. The Cohen Kappa coefficient was determined in addition to the Spearman Coefficient (ρ).

Results: We included 53 female patients, with an average age of 58 years, over 18 years of age who met the RA classification criteria of the ACR / EULAR. 65% had the highest level of education. The average time of illness was 18.4 years. 77.35% of the patients received treatment with Rituximab and 22.65% were users of Etanercept. The coefficients κ were determined for each HAQ domain: Dressing and Grooming: 0.53, Arising: 0.33, Eating: 0.51, Walking: 0.45, Hygiene: 0.46, Reach: 0.28, Grip: 0.35, Activities: 0.35, Sex: 0.59. All of them differ from the values found according to the Spearman correlation coefficient (ρ): 0.68; 0.53; 0.66; 0.68; 0.64, 0.55; 0.63; 0.57; 0.8 for each domain respectively.

Conclusions: A slight to acceptable agreement was found in the domains of the Peruvian version of the HAQ. The agreement can vary according to the statistical method used, being the most appropriate the kappa coefficient.

307

INFLIXIMAB, ADALIMUMAB AND ETANERCEPT, A FIVE-YEAR FOLLOW-UP FROM A REAL-WORLD COHORT

Omaira Valencia¹, and Pedro Santos². ¹Universidad De Los Andes, Bogotá D.C., Colombia, ²Biomab IPS, Bogotá D.C., Colombia.

Objectives: To compare the clinical outcomes by DAS28 results, in patients treated with Infliximab, adalimumab, and etanercept for five years, using real-world data.

Methods: A medical records review analysis from real-world data was performed for a cohort of adult patients living with rheumatoid arthritis (RA) who were treated with one of the three molecules during the last five years. Clinical outcomes were measured by DAS28 follow-up at least three times per year. Differences in the baseline (T0) and the fifth year (T1) were identified; the behavior of those outcomes during the period of analysis was also compared.

Results: One hundred and thirty-five patients were followed during the past five years, treated with Infliximab (n =51), Etarnecept (n=42) and adalimumab (n=42). The number of of patients clasified as low disease activity (LDA) at T0 and who were treated with infliximab was 35.29%, this percentage increased to 90.2% at the third year (T3) and it showed a decrease of 11.2 percentage points at the fifth year (T5) of treatment. Patients treated with adalimumab clasified as high disease activity decrease (HDA) from 4.7 to 0.0% at T3 and increase to 2.38% at T5; likewise, those who received etanercept were 16.5% of those with HDA at T0 and decrease to 0% in T3 untill T5. Diferences between T0 and T3 were significative, p<0.005 for all molecules.

Conclusions: The three molecules showed a peak of effectiveness at the third year of treatment; however, at the fifth year there was decreased ffectiveness as there were fewer patients in LDA. On the other hand, etanercept was the molecule for which there was no increase in the number of patients classified as HDA. It is important to develop another study with a bigger cohort of patients to evaluate survival rates in any medicationnand to recognize other factors related to these results.

308

TOFACITINIB AS AN ALTERNATIVE TREATMENT IN PATIENTS WITH RHEUMATOID ARTHRITIS AND DEMYELINATING DISEASE

Hugo Javier Madariaga Charaja¹, and Maria Elena Luza¹. ¹Hospital III Yanahuara EsSalud, Arequipa, Perú.

Objectives: To report a case of cerebral demyelinating disease secondary to treatment with Etanercept in a patient with Rheumatoid Arthritis (RA) and the use of Tofacitinib as therapeutic alternative.

Methods: case report

Results: A 55-year-old woman, with a diagnosis of RA for 9 years, began treatment with methotrexate 15 mg and developed allergy, then she started sulfazalacin 1.5 g and also developed allergy, then she was switched to leflunomide associated with oral prednisone; however, she persisted with active disease. Etanercept 50 mg SC weekly was started. After 6 months of treatment she presented right side hemiparesis and a demyelinating brain mass was evidentnby MRI. Etanercept was stopped and patient treated with leflunomide associated with oral prednisone. At 9 months of follow-up, hemiparesis had resolved, and brain MRI findings were negative, but her RA was active (DAS-28: 6.3 CRP: 25 and ESR: 56 mm hour); so, treatment was started with tofacitinib 5 mg bid, achieving remission of the disease at 4 months (DAS-28: 2.5).

Conclusions: - Demyelinating disease is a recognized adverse event of biologics including anti- TNFs such as Etanercept. After this event it is difficult to decide which treatment to continue.

- Tofacitinib would be a good alternative treatment, demyelinating disease has not been reported with this medication.

309

FELTY’S SYNDROME, A CASE REPORT

Diana Carolina Dávila Cruz¹. ¹Hospital IESS Puyo, Ecuador.

Objectives: Introduction: rheumatoid arthritis (RA) is a relatively frequent autoimmune disease, with systemic involvement in joints as well as outside them. Within the extraarticular manifestations, there is the Felty’s syndrome (< 1 %) which is characterized bythe triad: RA, neutropenia and splenomegaly.

Targets: Presentation of a case of a patient with Felty’s syndrome.

Methods: Presentation of the Case: Woman 74 years old with history of: Type 2 Diabetes Mellitus, arterial hypertension, hypothyroidism, horseshoe kidney. RA diagnosed 15 years before. Receiving treatment with methotrexate 10 mg weekly, prednisone 5 mg daily. Over the last 8 months patient presented frequent and recurrent urinary tract infections. Neutropenia was observed. An abdominal ultrasound demonstrated mild-moderate splenomegaly. Peripheral blood smear did not reveal abnormalities. The hematologist confirmed our diagnostic suspicion of Felty’s syndrome. Treatment was optimized with Metrotexato 20 mg weekly and corticosteroids.

Results: From the beginning of the treatment the patient presented a neutrophil count of 560, without anemia or thrombocytopenia. She received 3 days methylprednisolone 125 mg and her methotrexate dose was increased; 5 days later her neutrophil count was 3770.

Later she was discharged on 20 mg of methotrexate, weekly, chloroquine, and prednisone to decreasing doses; at present on 5 mg po per day. 7 months later her neutrophil count has been above 1800 (except in 1 occasion); she has not presented new infectious events since then.

Conclusions: It is interesting to present a case of a rare RA complication, which sometimes can be -underdiagnosed. Antirheumatic drugs are used to treat neutropenia.

In all cases in which this syndrome is suspected, it is essential to rule out pseudo-Felty.

311

PERCEPTION OF THE RELATIONSHIP BETWEEN LIFESTYLE AND RHEUMATOID ARTHRITIS

Araceli Bernal Gonzalez¹, Gabriela Peza Cruz², Mayra Beatriz Naranjo Torres³, Angelica A. Peña Ayala⁴, Hector Garcia¹, Jaime Mendoza Torres¹, Luis Rodriguez Delgado¹, Jessica Gutierrez¹, Leticia Hernandez Gonzalez¹, Denice Clavijo Cornejo¹, Marwin Gutierrez¹, and Carlos Pineda¹. ¹Instituto Nacional de Rehabilitación, Tlalpan, Mexico, ²Facultad de Enfermería, Universidad Autónoma de Querétaro, Querétaro, México, ³Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México, ⁴Hospital General Regional NO. 1 IMSS, Querétaro, México.

Objectives: To determine the relationship between lifestyle and the degree of activity of the disease of subjects being cared for at a third-level outpatient clinic of the Rhebailitation Institute in Mexico City.

Methods: Descriptive, cross-sectional study in subjects with RA, selected for convenience. After informed consent, the lifestyle profile instrument (PEPSI-I) of Nola Pender, validated in Mexico by Bezares-Sarmiento et al. (2014) was applied. This instrument has a Cronbach alpha of 0.92, of 48 items, divided into six dimensions: nutrition, exercise, responsibility for health, stress management, interpersonal support, self-actualization; there are four possible numerical scale response forms: from 1 to 4 (1. Never, 2. Sometimes, 3. Frequently, 4. Routinely), to assess the frequency of performing the behavior, in patients older than 18 years of age. To estimate RA activity, the DAS28 (disease activity score) score was used as the measurement method. The data obtained were treated by descriptive statistics.

Results: Preliminary data in 10 patients, 100% women, average age 49 years, 80% have basic education, 13 years as a mean disease duration 40% did not perform physical or recreational activity, 40% smoked and 100% referred not to drink alcoholic beverages. By DAS28 40% present disease activity. Regarding the dimensions of lifestyle, for nutrition 60% chose foods that included the 4 basic groups of nutrients; for exercise, 80% never participate in physical activities, 60% never use specific methods to control tension (nerves) in the management of stress. For the responsibility for their own health, 80% sometimes attended educational programs about health care’ for the interpersonal support, 80% sometimes liked to express their feelings or have them expressed by people close to themfor self-actualization 60% are enthusiastic, optimists in their life, 24% are realistic in their goals

Conclusions: Behavioral patterns harmful to health are also reflected, as well as the coexistence of a relationship of non-work activity due to positive RA, being of high priority for the multidisciplinary health care team, direct actions that help patients to achieve remission of the disease and maintain that state of remission as long as possible. Within this range of actions, nursing has a great responsibility to undertake health-promoting interventions that strengthen the dimensions of lifestyle and allow RA patients to consolidate their self-care to improve their quality of life.

313

ASSOCIATION OF OBESITY WITH LOWER RATES OF REMISSION IN A COLOMBIAN COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS

Jorge Bruce Flórez Suárez¹, Paul Méndez Patarroyo^1,2, Paola Ximena Coral Alvarado^1,2, Edna Bermúdez¹, and Gerardo Quintana López^1,2,3. ¹Grupo REUMAVANCE, Seccion de Reumatología, Hospital Universitario Fundacion Santa Fe De Bogotá, Bogotá, Colombia, ²Facultad de Medicina, Universidad de Los Andes, Bogotá, Colombia, ³Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.

Objectives: Modifiable risk factors associated with the severity of Rheumatoid Arthritis (RA) have been studied, including the body mass index (BMI). There is evidence that obesity favors a pro-inflammatory environment. Adipose tissue has an increased presence of infiltrating macrophages, which are responsible for the increased production of inflammatory molecules, that are correlated with a worse disease activity, and a lower response to treatment. The aim of this study was to compare the course of disease activity during 24 months of follow-up in different initial BMI groups of Colombian RA patients.

Methods: The study used a cohort of Colombian patients with RA (Satisfying ACR/EULAR classification criteria). Patients were classified based on their initial BMI category (Normal weight, Overweight, and Obese). Disease activity based on DAS-28 ESR, and BMI were collected during 24 months of follow-up. The achievement of sustained remission was also registered. At 24 months, the patients from every BMI category, were re-classified based on their BMI calculated at the last visit. The proportion of patients on every BMI category was calculated. For every initial BMI category, mean differences between the initial DAS-28 and the one at the 24 months of follow-up for the re-calculated BMI category, were calculated using Kruskal-Wallis test. Survival analysis for the achievement of sustained remission during the 24 months of follow-up for every initial BMI index category was developed. Mantel-Cox test was calculated to compare the survival curves between initial BMI category groups.

Results: A total of 270 patients were included. The majority of the patients were at the Normal weight category (n=111), followed by overweight (n=107). Mean age was 53.38 years. Mean initial DAS-28 for every group was within moderate activity category. Normal weight group had the highest score (DAS28=4.01), while the overweight group had the lowest (DAS28=3.71). The decrease in disease activity was greater for patients with initial Normal BMI. This group was the only that achieve remission scores at the end of the follow-up period, while overweight patients remain with low disease activity. The obesity group had the highest DAS-28 at the end. Sustained remission was achieved by 58% of patients from the Normal weight group, 57% of overweight group, and 42% of obese group. When comparing the survival curves of normal and obese groups, they were significantly different (p=0.0209). Mantel-Cox test result was statistically significant.

Conclusions: In this RA cohort of Colombian patients, those with initial obesity were less likely to achieve remission compared to patients who were initially overweight or who had a normal weight, during the 24 months of follow-up. These results are evidence of the importance of assessing and making an early intervention on the weight and habits of patients with RA, in order to increase the odds of achieving good control of their disease.

314

ACPA EXPRESSION IN RHEUMATOID ARTHRITIS AND PERIODONTAL DISEASE AT A SECOND LEVEL HOSPITAL

Blanca Carlos Mancilla¹, Éufrates Hernández Núñez², and Francisco Olàn². ¹Hospital Gustavo A. Rovirosa Pèrez, Villahermosa, Mexico, ²Villahermosa, México.

Objectives: ACPA expression in patients with rheumatoid arthritis (RA) and periodontitis (PO).

Methods: Cross-sectional and descriptive study. Population: 100 patients with a diagnosis of RA were studied. Their levels of anti CCP antibodies were quantified, and dental evaluation was carried out; of which 50 met the inclusion criteria. The variables used were Gender, age, disease duration (years), monoclonal antibody

ACPA values, family history of RA and Smoking.

Results: The prevalence of RA associated with PO was 30% (15); 6% of the patients were men and 94% women. The average patients’ age was 48.4 years with a range of 22 to 69 years. Patients under treatment with Biological agents had lower ACPA titers. The expression of anti CCP antibodies and the clinical presentation of both diseases was higher, predominating in women; more than half of the patients with a disease duration of 5 to 10 years had high ACPA values. Patients with high ACPA titers, who still did not have PO, presented Gingivitis, pulpitis and dental caries. Of the 30% of the patients who presented both diseases, 20% were smokers and 20% has a family history of RA. Immunogenicity was found in 2 family lines.

Conclusions: In patients with RA, PO was more prevalent; ACPA have been detected with great specificity in the serum and synovium of patients with RA. Early synergistic interventions that modulate host response can significantly improve these patients’ quality of life; treatment approaches against bacterial etiology may be considered.

315

RHEUMATOID ARTITIS ACTIVITY AND ABNORMALITIES OF GLUCOSE METABOLISM AT A SECOND LEVEL HOSPITAL

Blanca Carlos Mancilla¹, Éufrates Hernández Núñez¹, and Francisco Olàn¹. ¹Hospital Gustavo A. Rovirosa Pèrez, Villahermosa, México.

Objectives: Describe glucose abnormalitiesin patients with rheumatoid arthritis (RA) quantified with anti -CCP and RF.

Methods: Cross-sectional, descriptive study. Population: 170 patients, with a diagnosis of RA, double seropositive for RF, and anti-CCP antibodies) were studied. Measurement of glucose tolerance curve was done. 52 patients met the inclusion criteria; variables used were glucocorticoid use, high levels of ACPA, disease activity by DAS-28 and SDAI, simultaneous measurement of oral glucose tolerance test.

Results: Glucocorticoids (GC) were a common drug used for the treatment of RA; more than 50% of the patients had an impaired oral glucose tolerance test. Patients with RA treated with oral GC are at risk for DM; the 25-30% increase in the risk of DM was associated with each additional 5 mg of the current oral GC dose, while only the doses of CG taken persistently for 6 months are closely associated with the risk of DM.Double-seropositive patients (RF, anti-CCP) presented higher systemic / articular inflammation and clinical activity that those who expressed other combinations of autoantibodies (p <0.001).

Conclusions: Systemic inflammation in patients with RA plays an important effect on glucose metabolism; long-term inflammatory status could lead to cell dysfunction and apoptosis and affect the hepatic metabolism of glucose.Patients with glucose metabolism abnormalities after GC treatment generally had a longer disease duration than those without abnormalities; this is consistent with the aforementioned statement that the extension of the inflammatory state could increase the sensitivity to insulin and the negative effects on β cellular function.

332

VARIABILITY IN THE DEFINITION OF THE ARTICULAR EXAMINATION OF RHEUMATOID ARTHRITIS: RESULTS OF A SURVEY CONDUCTED IN A GROUP OF COLOMBIAN RHEUMATOLOGISTS

Yimy Medina¹, M.I. Narváez-Reyes¹, J.A. Atuesta-Rodríguez¹, C.A. Calderón-Cordero¹, O.Y. Motta-Quimbaya¹, and F. Rondón-Herrera¹. ¹National University of Colombia, Bogotá, Colombia.

Objectives: The follow-up of patients with rheumatoid arthritis (RA) is based on the joint count using different scales. They allow the rheumatologists to determine the activity of the disease and classify its severity of, but scales are very variable and not very reliable among examiners.

Methods: A 30-question survey was applied to 91 rheumatologists who attended the Colombian Congress of Rheumatology in the city of Bucaramanga in March 2017. The questions asked about general aspects of the physical examination, technique to determine pain and joint inflammation during the clinical evaluation, and how to explore different joints.

Results: There was an important disagreement between rheumatologists. 78% of rheumatologists considered three important aspects when assessing pain. There was no consensus about the order of the joint examination.

There was no agreement in the technique to examine the joints. The need to reach a consensus on how to perform joint examination in patients with rheumatoid arthritis was agreed by 86.8% of the rheumatologists. Most of them believe there is not enough literature on the subject. Despite the fact that the European League Against Rheumatism (EULAR) determined the technique of joint examination through the publication of a book, there is no solid evidence of the technique and the fundamentals of its performance.

Conclusions: The joint examination of the activity in rheumatoid arthritis is the fundamental basis in the diagnosis, treatment and prognosis of this disease. However, there is no agreement among rheumatologists in its definition and application.

333

MEASUREMENT OF GLOBAL HEALTH PERCEPTION BY DIFFERENT SCALES IN PATIENTS WITH RHEUMATOID ARTHRITIS AND A COMBINED SCALE PROPOSED

Yimy Medina¹, Eybar Diaz-Ibarra¹, M.I. Narváez-Reyes¹, J.A. Atuesta-Rodríguez¹, C.A. Calderón-Cordero¹, O.Y. Motta-Quimbaya¹, F. and Rondón-Herrera¹. ¹National University of Colombia, Bogotá, Colombia.

Objectives: The global perception of health (PGA) is part of the compound instruments used to determine the activity of Rheumatoid Arthritis (RA), usually measured with the visual analog scale (VAS). In clinical practice and in the literature, difficulties have been observed in the application of the VAS, considering the need to define the performance of the different scales to evaluate PGA, determine the ease of use and propose a new scale.

Methods: Study based on the outcome of patients, subjects diagnosed with RA, to whom 4 types of scales were applied to evaluate PGA: scale 1 (VAS), scale 2 (face scale), a proposal of visual scale in two versions: scale 3 (composite visual scale in horizontal orientation) and scale 4 similar to 3 in vertical orientation.

Results: 198 patients were included, 169 women (85.3%), 29 men (14.6%), mean age of 54.2 years. 59.6% of the patients did not understand the scale 1, the majority of the patients understood the scales 2,3 and 4, approximately 80% of the patients preferred the scales 2 (43.4%) and 3 (36, 3%) (p <0.00), no clinical variable predicted the selection of the scale. A good concordance and an acceptable reproducibility of scales 2,3 and 4 were observed.

Conclusions: The majority of the patients did not understand VAS used in scales like the DAS28 and, preferred the proposed scales, mainly which combine faces and numbers (scale 2) that could be useful in the clinical practice of patients with RA.

This resource is a valuable in the evaluation of the PGA for patients who have difficulty inunderstanding the VAS.

4. SPONDILOARTHRITIS AND OTHER INFLAMMATORY ARTHROPATHIES

19

THE RELATIONSHIP BETWEEN BLOOD EOSINOPHIL COUNT AND DISEASE ACTIVITY IN ANKYLOSING SPONDYLITIS PATIENTS TREATED WITH TNF-Α INHIBITORS

Taskin Senturk¹, Gokhan Sargin¹, and Irfan Yavasoglu². ¹ Adnan Menderes University, Dept of Rheumatology, Aydin, Turkey, ² Adnan Menderes University, Dept of Haematology, Aydin, Turkey

Objectives: Anti-tumor necrosis factor-alpha (Anti-TNF-α) therapy has achieved an important position, are widely used for ankylosing spondylitis (AS) patients. TNF-α inhibition improves clinical outcomes and has differential effects on haematopoiesis. Information about effects on eosinophils is limited. The aim of our study was to determine the relationship between blood eosinophil counts in AS patients treated with TNF-α inhibitors.

Methods: Seventy-five patients diagnosed with AS according to the modified New York criteria were enrolled in this study. Disease activity was assessed by the BASDAI; erythrocyte sedimentation rate and C-reactive protein were evaluated. All data were analyzed with Spearman’s correlation and Friedman's Two-Way by using SPSS version 19.0 statistical software, and p<0.05 was considered as statistically significant.

Results: Seventy-five AS (F/M: 27/48, the age of 41 (10 years) patients were evaluated. On the 3th month of treatment, there was a correlation between BASDAI and CRP (r=0.32, p=0.005), but no correlation between BASDAI and ESR (r=0.21, p=0.06). Blood eosinophil count was not correlated with BASDAI, ESR and CRP on pre-, post-therapy (p>0.05). Eosinophil counts were lower before anti-TNF-α therapy compared with post-treatment (130/mm3, 140/mm3 and 190/mm3, respectively). There was no statistically significant difference between pre- and 3rd month blood eosinophil count (p>0.05), while significant correlations were found between pre- and 6th month, and 3rd and 6th months (p<0.001, p=0.002, respectively).

Conclusions: To the best of our knowledge, our study is the first to evaluate blood eosinophil counts and disease activity with anti-TNF-α therapy. Blood eosinophil count may be affected by TNF-α inhibition in patients with AS.

36

FRAGILITY FRACTURES IN PSORIATIC ARTHRITIS PATIENTS: A MATCHED-CONTROL STUDY

Luciano Lo Giudice¹, Nicolas Martin Marin Zucaro¹, John Fredy Jaramillo Gallego¹, Florencia Sabina Pierini¹, Marina Scolnik¹, and Enrique Roberto Soriano Guppy¹. ¹Hospital Italiano De Buenos Aires, Ciudad Autónoma De Buenos Aires, Argentina

Objectives: Patients with Psoriatic Arthritis (PsA) in spite of having bone production as one of their characteristic features, very often have osteoporosis, but scarce data is available on fracture risk. Our objective was to compare incidence of osteoporotic fractures in PsA patients diagnosed after the year 2000 with matched controls from a university hospital-based health management organization (HMO).

Methods: Consecutive PsA patients diagnosed after the year 2000, from the HMO, were matched (age and sex) with controls (1:2). The follow-up period began at the first medical claim at the HMO. Subjects were then followed until they voluntarily left the HMO, a fracture occurred, the end of study (May 1st, 2018), or death. Electronic medical records were reviewed and demographic, clinical and treatment data were collected. Incidence rates per 1000 persons-years (PY) of distinct types of fractures after index dates were calculated and compared between groups. A multivariate Cox regression analysis was performed to investigate determinants of fractures.

Results: 92 PsA patients and 184 controls were included. 8.7 % (95% CI 4.4-16.5) of PsA patients had axial involvement. Topical corticosteroids were used by 60.9% (95% CI 50.5-70.4) of PsA patients and 22.8% (95% CI 15.3-32.6) received oral corticosteroids. No difference was found in the overall fracture incidence rate per 1000 PY between PsA and controls (10.2, 95% CI 5.1-19.3, vs 8.7, 95% CI 5.2-13.9, p=0.36). Vertebral fractures were more frequent in PsA patients with an incidence rate of 10.2 per 1000 persons-years (95% CI 5.1-19.3) versus 4.6 per 1000 persons-years in the control group (95% CI 2.4-9.2), but it did not reach statistical significance (p=0.06). In the Cox regression analysis, after adjusting for bisphosphonate use, only age (HR 1.10, 1.05-1.16, p < 0.001) and female sex (HR 3.94, 1.11-13.91, p =0.03) were associated with fractures while PsA diagnosis and use of corticosteroids were not.

Conclusions: in this cohort of PsA patients diagnosed after the year 2000, no overall increased risk of fractures was found in comparison with matched controls. This may be due to a rational use of corticosteroids.

51

TREATMENT PREFERENCES OF PATIENTS WITH AXIAL SPONDYLOARTHRITIS (AXSPA)

Dafne Capelusnik¹, Emilce Edith Scheeberger¹, Lysett Macías Oviedo¹, Juan Sevillanos¹, Gustavo Citera¹. ¹ Irep, Caba, Argentina

Objectives: To evaluate the treatment preferences of patients with Axial Spondyloarthritis (axSpA) and to identify the factors associated with their choice.

Methods: Patients diagnosed with axSpA (ASAS 2009 criteria) were included. Sociodemographic data, disease characteristics, comorbidities, disease duration, disease activity and treatments received were recorded. A specially designed questionnaire in both, multiple choice modality and response mode listed in order of priority of the statements was administered to evaluate patient preference for drug administration, doses frequency, the favorite site and the person chosen for drug administration. Also, the attributes and disadvantages of the chosen rout were assessed, as well as the characteristics and compliance with the current treatment.

Statistical analysis: Descriptive statistics. Student's T-test, Chi square test and multiple logistic regression analysis. A value of p <0.05 was considered significant.

Results: Seventy patients were included with a median age (m) of 46.5 years (IQR 38-57), 55 males (78.6%) and a m disease duration of 13.5 years (7.75-23.25).

The relevant aspects in decreasing order of frequency for choosing a treatment were: the ability to improve quality of life (32.9%), improvement in joint inflammation (22.9%), pain (21. 4%) and physical function (14.3%). Sixty-three patients (90%) chose to receive the medication at home, and 55 (78.6%) chose to self-administer the drug. The most chosen mode of administration was oral (51.4%), following by subcutaneous (SC) (41.4%). The preferred frequency of oral administration was one tablet per week and SC administration, once a month. The choice of oral route was associated with: preference for self-administration, preference for receiving the medication at home and higher level of education.

Conclusions: The most preferred way of administration in patients with axSpA was the oral route, with a weekly frequency and self-administration at home, followed by the subcutaneous route, with monthly infusion.

69

TEN-YEAR RETENTION RATE OF FIRST-LINE ETANERCEPT IN AXIAL SPONDYLARTHRITIS: A ROMANIAN MULTICENTRE EXPERIENCE

Codrina Ancuta¹, Eugen Ancuta², Rodica Chirieac³, Codruta Bran⁴, Claudia MIhailov⁵. ¹Grigore T Popa University Of Medicine And Pharmacy Iasi, Iasi, Romania, ²Elena Doamna Clinical Hospital, Research Department, Iasi, Romania, ³SANOCARE Medical & Research Center, Iasi, Romania, Iasi, Romania, ⁴Sf.Ioan cel Nou Emergency Hospital, Suceava, Romania, Suceava, Romania, ⁵Ovidius University Constanta, Romania, Constanta, Romania

Objectives: Efficacy and long-term persistence on TNF inhibitors (TNF-i) are widely recognized in axial spondyloarthritis (axSpA); however, about one third of patients experience failure at first biological agent requiring switching to another drug.

The aims of our study were to assess the 10-year survival of etanercept (ETA) and to identify factors associated with drug retention.

Methods: We performed a medical records review analysis of consecutive active axSpA suboptimally controlled by standard therapy, receiving ETA as their first TNF-i according to local recommendations at 3 Romanian centres. Drug efficacy (BASDAI, ASDAS-CRP) as well as reasons for discontinuation were evaluated every 24 weeks.

Drug survival was calculated by the Kaplan-Meier analysis, and univariate and multivariate regression was used for predictors of persistence and withdrawal (p<0.05) (SPSS19, EXCEL2010).

Results: 88 patients out of 241 axSpa taking biologics received ETA as first biological agent.

Statistically significant improvement was demonstrated (ASDAS-CRP, BASDAI, BASFI) in all patients, those with higher disease activity and functional impairment at baseline presenting earlier and higher response rate (p<0.05).

We reported high log-term persistence of ETA, with median survival rate of 8.1+/-2.1 years and a total drug-exposure of 625.43 patient-years; furthermore, at 10 years, up to one third (36.36%) of axSpA remained on the initial ETA achieving either stable remission (62.5%) or low disease activity (37.5%).

Male sex, age under 40, high baseline C reactive protein, low initial BASFI and disease duration under 5 years were associated with a therapeutic response (p<0.05), while syndesmophytes and obesity with higher withdrawal (p<0.05).

Reasons for ETA discontinuing were loss of drug efficacy (85.71%), paradoxical reactions (4 uveitis, 1 Crohn’s disease), latent TB reactivation (2), injection site reactions (3).

Conclusions: In conclusion, we reported good long-term persistence of the first biological agent (ETA) in axSpA as well as certain predictors for high retention rate offering the rationale for this drug choice in different disease settings.

101

EFFECTIVENESS AND SAFETY OF INFLIXIMAB AND GOLIMUMAB IN ANKYLOSING SPONDYLITIS FROM A LONGITUDINAL OBSERVATIONAL REGISTRY

Proton Rahman¹, Derek Haaland², Dalton Sholter³, Michael Starr⁴, Artthur Karasik⁵, Michelle Teo⁶, Sanjay Dixit⁷, Ariel Masetto⁸, Anna Jarosynska⁹, Pauline Boulos¹⁰, Emmanouil Rampakakis¹¹, Odalis Asin-Milan¹², Allen J. Lehman¹², and Francois Nantel¹². ¹ Memorial University, St John's, Canada, ² Waterside Clinic, Barrie, Canada, ³ Rheumatology Research Association, Edmonton, Canada, ⁴ McGill University, Montreal, Canada, ⁵ Private practice, Toronto, Canada, ⁶ Private practice, Penticton, Canada, ⁷ The Arthritis Centre, Burlington, Canada, ⁸ Centre Hospitalier de l'Universite de Sherbrooke, Sherbrooke, Canada, ⁹ Private practice, Oakville, Canada, ¹⁰ Private practice, Dundas, Canada, ¹¹ JSS Medical Research, Montreal, Canada, ¹² Janssen Inc, Toronto, Canada

Objectives: To describe the profile of ankylosing spondylitis (AS) patients treated with infliximab (IFX) or golimumab (GLM) treatment in Canadian routine care along with its long-term effectiveness and safety.

Methods: 810 AS patients treated with IFX or GLM were enrolled into the Biologic Treatment Registry Across Canada (BioTRAC) registry between 2005-2015 and 2010-2017, respectively. Study visits occurred at baseline and every 6 months thereafter, as needed per routine care. Effectiveness was assessed with changes in ASDAS, BASDAI, BASFI, MDGA, HAQ-DI, PtGA, back pain and acute phase reactants. Safety was evaluated with the incidence of adverse events (AEs) and drug survival rates.

Of the 389 IFX- and 421 GLM-treated patients, the proportion of males were 62.7% and 59.1%, the mean age were 45.6 and 45.7 years and the mean disease duration were 8.6 and 6.0 years, respectively. Most patients were bio-naive (>82.7%). Interestingly, we observed a significant decrease in disease duration in the IFX cohort from a median of 8.0 to 3.5 and 1.0 years in 2005-2008, 2009-2012 and 2013-2015, respectively (p<0.001).

Results: Treatment with both IFX and GLM significantly improved all disease parameters over time (p<0.001) from baseline up to 120 and 84 months, respectively, with similar efficacy between agents.

AEs were reported for 67.9% and 70.5% (136 and 131 events/100 PYs) and SAEs for 15.4% and 8.1% (10.5 and 22.7 events/100 PYs) covering 1251.3 and 674.8 years of exposure for IFX- and GLM-treated patients, respectively. The most frequently occurring AEs (>7% of patient in either group) were upper respiratory tract infection, arthralgia and back pain. Two deaths occurred in IFX-treated patients (myocardial infarct, drowning) and two among GLM-treated patients (oropharyngeal cancer; neutropenia, staphylococcal/pseudomonas infections, septic shock).

The proportion of patients who discontinued treatment were 65.8% over a mean 3.2 years of exposure in the IFX cohort and 56.8% over 1.6 years in the GLM cohort.

Conclusions: Both IFX and GLM treatment significantly reduced disease activity and improved functionality in a similar fashion and were well tolerated in patients with AS. Differences in baseline characteristics over time demonstrate improvement in early diagnosis of AS and earlier access to biologic therapies.

125

ADVERSE EVENTS OF BIOLOGICAL DRUGS IN SPONDYLOARTHRITIS, DOMINICAN REPUBLIC

R. Jimenez-Candelaria¹, M. Marte-Robles¹, L. Concepcion-Sanchez¹, E. Rosario-Guzman¹, E. Rodriguez-Bautista¹, V. Rosario¹, R. Muñoz-Louis¹, T. Valdez-Lorie¹, and R. Alba-Fériz¹. ¹Hospital Docente Padre Billini, Santo Domingo, Dominican Republic

Objectives: To describe the adverse events in patients with SpA treated with biological disease-modifying antirheumatic drugs (bDMARDs).

Methods: This was an observational cross-sectional study. Data was collected from the digital records of the Hospital Docente Padre Billini’s Rheumatology service during the period of July - December 2018. Inclusion criteria: age ≥ to 18 years, with at least 2 visits per year that met the ASAS group criteria, treated with bDMARD. A mild adverse event that considered when a patient did not have to discontinue the drug and a serious one if it required admission to the hospital or drug discontunation. The data were analyzed with SPSS V23 for Windows 10.

Results: We have 166 patients with SpA. 50.4% (55) were women, 72.4% (79) had an average age of 45 years, 36% (40) were psoriatic arthritis, 35.1 % (39) ankylosing spondylitis, 11.7% (13) reactive arthritis, 10.8% (12) undifferentiated SpA, 4.5% (5) axial non-radiographic SpA, 1.8% (2) SpA associated with inflammatory bowel disease. 63% (70) had less than 5 years of disease duration, 23.4% (26) were HLA B27 positive, 4.5% had (5) uveitis, 4.5% (5) dactylitis. 55.8% (62) were on therapy with a bDMARD; the distribution was as follows: 39.6% (44) adalimumab, 9% (10) etarnecept, 4.5% (5) golimumab, 1.8% (2) certolizumab pegol, 0.9% (1) secukinumab 63%. AE were: 34.2% (38) dyslipidemia, 13.5% (15) hypertransaminemia, 9% (10) neutropenia, 3.6% (4) lymphopenia, 1.8%, had severe AE; 2.7% (2) had a lower airway infection and (1) pulmonary tuberculosis (PTB). 39.6% (44) used DMARDs, 45% (50) steroids at low doses, 34.2% (38) NSAIDs.

Conclusions: Our study reported 63% of AEs, of which only 0.9% of them being serious; this differs from other studies in which 15.4% have been reported. serious adverse event corresponded to a case of PTB, despite being an endemic country of this disease. Serious infections and AEs were presented with adalimumab. This is the first epidemiological study for AE in SpA registered in this country, which forms the basis for further statistical studies.

126

SPIROMETRIC FINDINGS IN RELATION TO THORACIC EXPANSION IN PATIENTS WITH ANKYLOSING SPONDYLITIS, DOMINICAN REPUBLIC

R. Jiménez-Candelaria¹, M. Marte-Robles¹, L. Concepcion-Sanchez¹, E. Rosario-Guzman¹, E. Rodriguez-Bautista¹, V. Rosario¹, R. Muñoz-Louis¹, T. Valdez-Lorie¹, and R. Alba-Fériz¹. ¹Hospital Docente Padre Billini, Santo Domingo, Dominican Republic

Objectives: To describe spirometric findings in relation to thoracic expansibility in patients with ankylosing spondylitis.

Methods: Longitudinal, observational, cross-sectional study. The data were collected from the ankylosing spondylitis database of the Hospital Docente Padre Billini’s Rheumatology service during the period July - December 2018; patients over 18 years of age were included, with at least 2 visits per year that met the ASAS group criteria. They were indicated in their last spirometry consultation, with a bronchodilator test and the thoracic expansibility were measured, as well as information on sociodemographic and clinical data. The data were analyzed with SPSS V23 for Windows 10.

Results: Of a total of 166 patients with spondyloarthritis, 39 were diagnosed with ankylosing spondylitis; 17 met inclusion criteria, 82.3% (14) were men, 58.8% (10) had an average age of 50, 47% (8) with less than 5 years of disease duration, 5.8% (1) smokers, 5.8% ( 1) alcohol users, 23.5% (4) hypertension and diabetes, 70.5% (12) HLA B27 positive; 94.1% were receiving biological treatment, 35.2% (6) classic disease modifiers e, 17.6% (3) steroids, 29.4% ( 5) NSAIDs; 47% (8) had a normal pattern in spirometry, 35.2% (6) had a restrictive pattern, 17.6% (3) an obstructive pattern, 76.4% (13) an abnormal thoracic expansibility.

Conclusions: A direct association between abnormal spirometry and decreased thoracic expansibility is demonstrated. 35.2% had a restrictive pattern, 17.6% an obstructive pattern, and 76.4% abnormal thoracic expansibility. We must continue to evaluate the clinical and sociodemographic characteristics of patients with ankylosing spondylitis, expand the investigation with a larger cohort, follow up these patients for a longer time, and continue investigating the possible complications associated with the disease.

175

PREVALENCE OF PINGUECULA AND PTERYGIUM IN PATIENTS WITH SPONDYLOARTHRITIS

Nestor Alfredo Flores Guzmán^1,2, Ana Guilaisne Bernard Medina¹, Ana Cecilia Méndez Magaña², Fernanda Rábago Alcalá², and Bety Muñoz Solorzano¹. ¹Hospital Civil De Guadalajara "Fray Antonio Alcalde", Guadalajara, México, ²Universidad de Guadalajara "Centro Universitario de Ciencias de la Salud", Guadalajara, México

Objectives: The objective is to determine the prevalence of pinguecula and pterygium in patients with SpA.

Methods: The study design used is an analytical cross-section and for which a collection card was developed to gather information on SpA criteria, clinical history, risk factors and clinical assessments by ophthalmologist using a slit lamp and caliper to identify pinguecula or pterygium, bivariate analysis with Chi square, Student's t and Odds Ratio.

Results: In this study, 119 patients were included, of which 88 (73%) presented pinguecula and pterygium 28 (23%), the main location of the pterygium was nasal more than temporal in both the right eye (77% vs 16%) and left eye (90% vs 4.5%); of the 4 risk factors studied, there was only association with working under the sun, it was found in 9 patients (32% p= 0.01) with pterygium.

Conclusions: Pinguecula is more frequent than the pterygium in patients with SpA. The location is more prominent on the nasal side in both lesions. Working under the sun is associated with risk of pterygium bu not of pinguecula.

186

ATTITUDE TO THE PRACTICE OF PHYSICAL EXERCISE IN PATIENTS WITH PSORIATIC ARTHRITIS

Andrea Lujan Coronel Ale¹, Carolina Ayelen Isnardi¹, Emilce Schneeberger¹, Gisele Luna¹, Tatiana Barbich¹, Marina Fornaro¹, Osvaldo Cerda¹, and Gustavo Citera¹. ¹Instituto de Rehabilitación Psicofísica IREP, Caba, Argentina

Objectives: Determine the attitude of patients with PsA to the practice of regular physical exercise and to identify possible associated factors.

Methods: Patients ≥18 years old with diagnosis of PsA according to CASPAR criteria were included. Sociodemographic data, comorbidities, current treatment and physical activity practice (type and weekly training time) were recorded. Weight, height, functional capacity (FC), pain, global disease assessment by the patient (PGA) and physician (PhGA)and Ps assessment by the patient (PPsA) using Numerical Visual Scale (NVS), joint count (66/68), dactylitis, enthesitis (MASES), Ps (BSA) and Acute Phase Reactants (APR): ESR (mm/h) and CRP (mg/dl) corresponding to the day of the visit were consigned. Composite indices: DAPSA-CRP and DAPSA-ESS and BMI were calculated. The presence of MDA was recorded. Quality of life (PsAQoL), functional capacity (HAQ-A) and Exercise Attitude Questionnaire-18 (EAQ-18) were administrated. The EAQ-18 consists in 18 items (Likert scale 0-4) and its result is 0-100, higher value reflects better attitude to exercise.

Results: 69 patients were included, 50.7% were women, a median age (m) of 57 years (IQR: 46-66). 27 patients (39.1%) were overweight and 31 (44.9%) obese. 44.9% of the patients performed physical activity. The median physical activity practice time was 2 hours/week (IQR: 2-4). The result of EAQ-18 was m 70.4% (IQR: 57.4-79.6), 68.1% had EAQ-18 ≥60. EAQ-18 correlated inversely with PPsA (Rho: -0.510) and regularly with pain, PGA, PhGA, HAQ-A and DAPSA-CRP. Patients with EAQ-18 ≥60% had higher comorbidities (53.2% vs 46.8%, p = 0.02), MDA (55.3% vs 18.2, p = 0.004), PPsA (X 19.2± 3.1 vs X 49.5± 34.1, p = 0.000), HAQ-A (X 0.66±0.7 vs X 1.1±0.8, p = 0.02). In the multivariate analysis, a good attitude to the practice of physical exercise remained independently associated with a better PPsA (OR: 0.96, p = 0.02) and the presence of MDA (OR: 3.9, p = 0.05).

Conclusions: Almost 70% of patients with PsA have a good attitude towards physical exercise, in spite of the high BMI, the presence of comorbidities and offunctional disability. The variables associated with a better attitude to the practice of physical exercise were the presence of MDA and the good self-evaluation of Ps.

191

EFFICACY AND SAFETY OF INTRAVENOUS GOLIMUMAB IN ANKYLOSING SPONDYLITIS PATIENTS WITH COMPLETE ANKYLOSIS: RESULTS THROUGH WEEK 52 OF THE GO-ALIVE STUDY

John D. Reveille¹, Soumya D. Chakravarty^2,3, Shelly Kafka², Kim Hung Lo⁴, Stephen Xu⁴, Diane D. Harrison⁴, Elizabeth C. Hsia^4,5, and Atul Deodhar⁶. ¹University of Texas McGovern Medical School, Houston, United States, ²Janssen Scientific Affairs, LLC, Horsham, United States, ³Drexel University College of Medicine, Philadelphia, United States, ⁴Janssen Research & Development, LLC, Spring House, United States, ⁵University of Pennsylvania, Philadelphia, United States, ⁶Oregon Health & Science University, Portland, United States

Objectives: The GO-ALIVE study assessed the efficacy and safety of intravenous golimumab (IV-GLM) in patients (pts) with ankylosing spondylitis (AS). ¹ An unmet need exists for the treatment of AS pts with complete ankylosis. We investigated efficacy, quality of life (QoL), and safety outcomes through 52 weeks (WKS) in the subset of AS pts with complete ankylosis (pre-determined to be <10% of the study population) after administration of IV GLM or placebo (PBO).

Methods: GO-ALIVE is a Phase 3, randomized, double-blind, PBO-controlled trial. Pts (n=208) had definite AS (per modified NY criteria), BASDAI ≥4, total back pain VAS ≥4, and CRP ≥0.3 mg/dL. Pts were randomized (1:1) to IV GLM 2 mg/kg at WKS 0, 4, and every 8 WKS or PBO at WKS 0, 4, and 12, with crossover to IV-GLM at WK16 through WK 52. The primary endpoint was ASAS 20 at WK16. Other outcomes included ASAS 40, BASDAI 50, ASAS 5/6, ASDAS responses (inactive disease, major and clinically important improvements), BASFI, BASMI, ASQoL, night and total back pain, and enthesitis (UCSF index [0-17]). Complete ankylosis of the spine was defined as syndesmophytes present at all intervertebral levels of the cervical and lumbar spine visualized on lateral-view spinal radiographs per principal investigator. Safety was assessed through WK60.

Results: In this post-hoc, descriptive analysis, the subset of pts (7 PBO, 5 IV-GLM) with complete ankylosis were all men, all positive for HLA-B27, 46-years mean age, and 9-years disease duration. At WK16, numerically greater proportions of IV-GLM pts achieved ASAS-5/6 response (40%), ASDAS-major-improvement (50%), ASDAS-clinically-important-improvement (60%), and ASAS-20 (60%) vs PBO (0% for each), with similar results for ASAS-40, and BASDAI-50.