RADIOGRAPHIC ANALYSIS OF THE MANDIBULAR ANATOMY IN PATIENTS WITH SYSTEMIC SCLEROSIS
Emma Silva Gallardo1,4, Olga Lidia Vera Lastra1,2, Armando Cendejas Suarez4, María del Pilar Cruz Domínguez1,2, and Diego Fernando Tatis Giraldo2,3. 1Centro Médico Nacional La Raza. Hospital de Alta Especialidad Dr. Antonio Fraga Mouret, México, México, 2Universidad Nacional Autónoma de México, México, México, 3Orthokinetic Training Center, Cali, Colombia, 4Dental Orthokinetics Clinic, Yuriria, México.
Abstract: Background and Aim: Systemic sclerosis (SSc) is characterized by excessive production of collagen in the skin and internal organs and vascular and immunological abnormalities. SSc leads to temporomandibular dysfunction (TMD), and craniocervical (CC) and craniomandibular (CM) dysfunction. The aim of this study was to compare each mandibular bone measurements and angles in panoramic and lateral cranial radiographs of SSc patients and healthy controls.
Methods: We studied 21 SSc patients and 21 healthy controls. The associations between mandibular resorption and TMD and clinical findings were examined. Three cranial radiographs were performed in all patients and controls. A quantitative analysis of the mandibular anatomy based on cephalometric analysis and functional equilateral triangles of Tatis™ using Orthokinetor Plus 2™ software was performed. Data were analyzed with Students’ t, Mann-Whitney U, and Chi square tests.
Results: We included 21 SSc and 21 controls, with 5 to 38 years of SSc disease duration. A reduction were found: in the length of both mandibular branches, right (69.01±7.50 vs 74.37±5.82 mm, p<0.05); left (67.32±9.63 vs 74.35±6.69 mm, p<0.05); left mandibular condyle (17.34±3.10 vs 20.35±2.88 mm, p<0.05); in the depth of both glenoid cavities, right (5.33±1.39 vs 6.67±2.54 mm, p<0.05), left (5.33±1.56 vs 6.86±2.31 mm, p<0.05), and in the right gonial angle (127.45±14.16 vs 118.47±5.52 mm, p<0.05). The maxillomandibular planes were hiperdivergent. The inferior functional equilateral resulted in smaller mandibles (3±2 vs 0±4 mm, p<0.05) and decreased mandibular movements.
Conclusions: Patients with SSc have involvement of the mandibular bones, mostly in the coronoid process, condylar head and mandibular angle that can be measured by cephalometric analysis of panoramic radiography.
REAL-WORLD EXPERIENCE OF SECUKINUMAB FOR AXIAL SPONDYLOARTHRITIS IN A PRIVATE HOSPTIAL
Carlos Carneiro1, and Nuno Fernandes1. 1Hospital Particular Algarve, Portimao, Portugal.
Objectives: Spondylarthritis (SpA) is a chronic inflammatory disease predominantly affecting the axial skeleton and possibly the peripheral joints and entheses with a major impact on quality of life. There is increasing evidence that IL-17A blockade can be effective in patients with active SpA. Our goal is to evaluate short term efficacy of secukinumab in the management of SpA.
Methods: Observational medical records review study of twenty-five patients with spondyloarthritis who were consecutively treated with 150mg of secukinumab during 12 months. Laboratory and clinical assessments were based on erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ankylosing Spondylitis Disease activity score (AS-DAS)-CRP and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded at baseline and at the 12- month follow-up visit.
Results: The study included 25 patients. The mean age was 43 years and the majority of patients had received a previous anti-TNF biologic treatment prior to secukinumab (78%). Both BASDAI and ASDAS-CRP showed a statistically significant reduction between the baseline and the 12 month visit (p< 0,0001). During the laboratory assessment ESR and CRP showed a significant decrease (p< 0,0005 and p< 0,0008 respectively). Patients had a mean (SD) Bath Ankylosing Spondylitis Disease Activity index global score of 4.96 (2.5). Among patients who experienced overall improvement in AS symptoms 24% reported overall symptom improvement within 4 weeks after receiving secukinumab and 50% within 3 months. No radiographic progression from using the Modified Stoke Ankylosing Spondylitis Spinal Score change from baseline < 2 was observed in 81% of patients received secukinumab after six months of treatment. Median pain VAS dropped from 8 at baseline to 3 IQR (p< 0,001) at 12 months. Functional Assessment of Chronic Illness Therapy Fatigue (FACIT) revealed an impressive improvement Only one patient stopped secukinumab due to lack of compliance. There were only two registered adverse events (one respiratory infection and one urinary tract infection – Candida infection).
Conclusion: Secukinumab has proven remarkable short-term effectiveness, regardless of the biologic treatment line. The safety profile of secukinumab was favorable and similar to previous studies in the phase III program. Further studies should be required in order to monitor its long term efficacy, safety and clinical response.
SCHNITZLER SYNDROME WITH SUCCESSFUL RESPONSE TO CANAKINUMAB
Pablo Finucci Curi1. 1Hospital San Martín, Paraná, Argentina, Paraná, Argentina.
Objective: Schnitzler syndrome is a rare disorder characterized by chronic urticarial rash and monoclonal gammopathy, accompanied by intermittent fever, arthralgia or arthritis, bone pain and lymphadenopathy, in which interleukin 1 (IL1) has a preponderant role. To report a case of Schnitzler syndrome with successful response to canakinumab, a selective inhibitor of IL-1β.
Materials and Methods: The case of a 48-year-old male who presented with a one-and-a-half year history characterized by pruritic urticarial lesions located in the trunk and upper and lower limbs, accompanied by arthralgia and intermittent fever is presented here. On physical examination he was thinned, asthenic and febrile, with pain on joint palpation, without swelling. In addition, urticarial rash located in the trunk and upper limbs, and bilateral inguinal adenopathies were found. The laboratory showed anemia of chronic disease, leukocytosis with neutrophilia, increased acute phase reactants, and IgM monoclonal hypergammaglobulinemia. Autoantibodies and viral serologies were all negative. A CT scan showed mild splenomegaly, bilateral inguinal adenopathies and increased bone density in the right iliac bone. A skin biopsy reported perivascular neutrophilic dermatitis, without vasculitis. The bone marrow biopsy revealed to be slightly hypercellular with dyshematopoietic changes, granulocytic hyperplasia and slight increase of plasmocytes, with no findings suggesting malignancy. Inguinal lymph node biopsy: follicular hyperplasia; numerous congestive capillaries and lymphoid follicles of prominent germinal centers that respected its architecture; no findings of malignancy. Blood, bone marrow and lymph node cultures for common germs, tuberculosis and fungi were negative. The patient had received different treatments combined with antihistamines, nonsteroidal anti-inflammatories, corticosteroids, colchicine and hydroxychloroquine, achieving partial and transient improvement of rash, persisting fever and poor general condition.
Results: Since patient met the criteria for Schnitzler Syndrome, it was decided to start treatment with canakinumab 150 mg every eight weeks, which showed a clear improvement within 5 days, with disappearance of skin lesions, fever and arthralgia.
Conclusion: The interest of this case lies in the excellent response of Schnitzler Syndrome to canakinumab, highlighting the importance of considering the diagnosis in patients with chronic urticarial rash and monoclonal gammopathy; to date very few such cases have been reported.
TRIAGE AND TELEREGULATOR RHEUMATOLOGIST - REDUCING SOCIAL COSTS
Varlei Serratto1, and Sérgio Kowalski1. 1Municipal Health Secretary of Curitiba, Curitiba, Brazil.
Objective: (1) To evaluate the decrease in the number of patients in the queue for a rheumatologist; (2) To evaluate the decrease in the waiting time for the first consultation; (3) To evaluate the cost reduction with medical consultations after the implementation of screening and teleregulation by a rheumatologist.
Materials and methods: Patients referred from Primary Health Care to rheumatology. Data analysis for first consultation with rheumatologist. Variables were number of patients in the queue, length of stay and costs of consultations. Source e-health of the Municipal Secretariat of Curitiba and DATASUS (Brazil). Compared data from 2013-2015 (supply and demand model) with data from 2015-2017 and 2017-2019 (triage and teleregulator rheumatologist).
Results: Between 2015 and 2019, there was a decrease in the queue from 6429 to 50 patients; a reduction from 600 to 9 days waiting for the first consultation with a rheumatologist and a 41% reduction in the costs paid for medical appointments.
Conclusion: Triage and teleregulator rheumatologist were effective in reducing the social cost of patients with rheumatic diseases.
CONSUMERS OF PSYCHOACTIVE SUBSTANCES AND CARRIERS OF HIV IN AN INFECTIOUS DISEASE HOSPITAL IN GUAYAQUIL, 2014-2015
Freddy Rodriguez Chato1. 1Ministerio de Salud Pública, Tonsupa, Ecuador.
Goals: To determine the prevalence of psychoactive substances consumption and carriers of the Human Immunodeficiency Virus (HIV), treated at the Infectious Disease Hospital of Guayaquil, José Daniel Rodríguez, between 2014 and 2015.
Materials and Methods: A descriptive, medical records review, cross-sectional and observational study was done. Variables documented in the medical records, age group, consumed substances and opportunistic diseases, among others.
The information was taken from the medical records of 1003 HIV positive patients from this hospital.
Discussion: The consumption of multiple psychoactive substances, mixed generally with alcohol, generates dependence, overdosing, diseases such as AIDS and death; this is recognized as a difficult challenge in public health. There is thus a population of high risk “hunted” for their age in the education system, which explains high school dropout rate and poor performance. Structuring preventive processes are needed.
The national studies about drug use in subjects ages12 to 65 years, carried out in 10976 HIV carriers, established an alcoholic beverage prevalence of 56,2%; higher in males (64,9%) between the ages of 15 to 49 years, while cigarette smoking prevalence was of 28,1% and the use of drugs was of 35,8% in men between the ages of 15 to 49 years. A study in Colombia established the first alcohol consumed occurred at a mean age of 15.9 and without being HIV+. Arango A., Vanegas C. (2014)
The consumption of psychoactive substances can be associated to poverty, lower educational level, marginality, etc., factors also related to HIV. The data presented do not allow to conclude the relationship between HIV infection and drug consumption. Other studies are needed to establish the relationship between them
LYME ARTHRITIS IN AMERICANS ONLY? EASTERN EUROPE’S FINDINGS
Agne Petrulioniene1, Daiva Radzisauskiene2, Arvydas Ambrozaitis2, Saulius Caplinskas3,4, and Algirdas Venalis1,5. 1Clinic of Rheumatology, Orthopaedics Traumatology and Reconstructive Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, 2Clinic of Infectious diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, 3Center for Communicable Diseases and AIDS, Vilnius, Lithuania, 4Mykolas Romeris University, Vilnius, Lithuania, 5State Research Institute Center for Innovative Medicine, Vilnius, Lithuania.
Background: Lyme borreliosis (LB) is an infectious disease with a wide range of clinical symptoms. Usual LB manifestations are: Erythema migrans, Neuroborreliosis, Lyme arthritis, Lyme carditis. The clinical view of the disease varies depending on geographical area. In North America it is usually Lyme arthritis, while in Europe, Erythema migrans and Neuroborreliosis predominate.
Objectives: To elucidate the frequency of different Lyme’s disease clinical syndromes in Lithuania (Eastern Europe). To find out the baseline characteristics of Lyme arthritis.
Material and Methods: We have analyzed the data from Vilnius University Santaros Clinics, Infectious disease center from all the adult patients, who were diagnosed with Lyme disease on the ambulatory setting between 2014-2017.
Results: 1009 patients were enrolled. Clinical syndromes of the disease were as follows: Erythema migrans 947 (94%), Lyme arthritis 32 (3%), Neuroborreliosis 24 (2%), Lyme carditis 4 (0.4%), Acrodermatitis 1 (0.01%). Lyme arthritis was more frequently diagnosed in women 28 (87.5%) than in men 4 (12.5%), age range 19 – 80, median age 55. Affected joints were: knee 13 (32.5%), hand 11 (27.5%), ankle 10 (25%), elbow 3 (7.5%), foot 2 (5%), wrist 1 (2.5%). In 2 cases information about which joint was affected was not recorded. Monoarthritis 15 (50%) to compare with oligoarthritis 15 (50%) (hand arthritis counted as an oligo, because there was no data about how many small joints were inflamed) appeared equally.
Conclusions: In Lithuania the main Lyme’s disease clinical syndrome is Erythema migrans. Lyme arthritis was seen 1, 33 times more often than Neuroborreliosis, other syndromes are rare. Lyme arthritis mainly manifests in middle age women as mono or oligoarthritis, the mostly affected joint is the knee. According to current knowledge about Lyme borreliosis, Lyme arthritis is a common entity for American rheumatologists, but these data show that the disease exists in the Eastern part of Europe, only less often.
ARE ANTI-RNP-A ANTIBODIES ASSOCIATED WITH THE DEVELOPMENT OF AUTOIMMUNITY?
Fernando Lozano Morillo1, Óscar Cabrera Marante1, Antonio Serrano Hernández1, Miriam Retuerto Guerrero1, Patricia Lavilla Villar1, Boris Anthony Blanco Cáceres2, Rosa González Crespo1, and Luis Morillas López1. 1Hospital Universitario 12 De Octubre, Madrid, Spain, 2Hospital Universitario Ramón y Cajal, Madrid, Spain.
Objectives: Anti-RNP-A antibodies are included in automated multiplex immunoassays for the detection of antinuclear antibodies (ANA) available in most centres, though a low specificity for autoimmune disease has been described and may be frequently present as a false positive in healthy subjects. The aim of this study was to investigate the potential association between those antibodies and the development of immune-mediated inflammatory diseases (IMIDs).
Methods: We performed a search for patients with at least one positive determination of anti-RNP-A antibodies in the absence of concomitant positivity for the rest of multiplex specificities (dsDNA, chromatin, ribosomal protein, SSA/Ro-52, SSA/Ro-60, SSB/La, Sm, Sm-RNP, RNP-68, Scl-70, Jo-1 and centromere B) using the BioPlex™ 2200 ANA screen assay (Bio-Rad, Hercules, CA) and also with negative AAN-IIF, from January 2012 to June 2016. Medical reports of patients were longitudinally reviewed up to October 2019 (minimal follow-up of 3 years up to 7 years) to find out if a previous diagnosis of IMID was present, the nature of clinical suspicion that motivated AAN determination and finally if a diagnosis of IMID was established.
Results: We found 310 patients with isolated anti-RNP+, of which 78 (25%) had already a previous diagnosis of IMID (38.5% RA, 11.5% IBD-related spondyloarthritides, 9.0% SLE, 7.7% PsA, 6.4% PMR, 5.0% Sjögren’s syndrome, 3.8% axial spondyloarthritis, 2.5% myositis, 2.5% antiphospholipid syndrome, 2.5% systemic sclerosis, 1.2% MCTD, 3.8% IBD, 5.1% other). Among 75% of patients without an IMID (n=232), in 76 of them (33%) we could not identify the reason for suspected such. In the other 156 (67%), most frequent reason of suspicion were arthritis/arthralgia (33.3%), skin rash (9%), unexplained neurological symptoms (7.7%), myopathy/elevated CK(5.1%), interstitial lung disease work-up (4.5%), nephritis work-up (3.2%), sicca symptoms (2.5%), inflammatory ocular diseases work-up (2%) and Raynaud’s phenomenon (2%).
Of 156 patients without initial diagnosis with suspicion of IMID, a diagnosis was established in 23 of them (14.7%) but only in 9 (5.8%) it was of an AAN-related connective tissue disease (1 SLE, 1 drug-induced SLE, 2 MCTD, 2 APS, 3 Sjögren). In the other 14 patients (8.9%) a diagnosis of another immune-mediated disease (5 PsA, 3 RA, 2 PMR, 1 axial SpA, 3 vasculitis) was done.
Conclusions: Though anti-RNP-A may be present in healthy subjects without any underlying autoimmune disease, our study shows that a small percent of patients with suspicion of IMID and isolated anti-RNP-A+ can develop an immune-mediated disorder after several years. These findings could justify a periodic follow-up in patients with high clinical suspicion of IMID.
CAN HLA TYPE I AND II ALLELES BE ASSOCIATED WITH THE CLINICAL SPECTRUM OF CHIKUNGUNYA INFECTION?
Daniel Augusto Martin Arsanios1, Juan C. Rueda1,2, Ana M. Santos1, Jose-Ignacio Angarita1, Eugenia-Lucia Saldarriaga1, Viviana Reyes1,3, Santiago Bernal-Macias1,3, Sofia Arias-Correal1, Nathalia Muñoz1, Jose Arias-Correal1, Ingris Peláez-Ballestas4, Mario H. Cardiel5, and John Londono1,3. 1Universidad de la Sabana, Bogotá, Colombia, 2Biosciences Programme, Faculty of Medicine and Engineering Universidad de La Sabana, Chía, Colombia, 3Rheumatology Department, Hospital Militar Central, Bogotá, Colombia, 4Rheumatology Unit, Hospital General de México "Doctor Eduardo Liceaga", México City, México, 5Centro de Investigación Clinica De Morealia Sc, Morelia, México.
Objectives: Virulence factors as well as host immune response play an important role in disease susceptibility via the Human Leukocyte Antigen (HLA). There are no known studies associating the presence of HLA class I and II alleles with the chikungunya virus (CHIKV) infection in Latin America. Based on the population included in Community Oriented Program for the Control of Rheumatic Diseases (COPCORD), this study was developed to identify which HLA alleles are present in patients with CHIKV infection and their association with the clinical spectrum of the disease.
Materials and Methods: This was a cross-sectional analysis nested in a community cohort including patients aged > 18 years. Patients from the COPCORD study who met the definition of CHIKV infection (WHO criteria and ELISA IgG and/or IgM) were included. HLA typing of HLA-A, HLA-B and HLA-DRB1 alleles was performed. Two-by-two tables were used to establish associations between allele presence and clinical characteristics.
Results: Of the 6528-people surveyed in the COPCORD study, 548 (8.4%) were included in our study as suspected for CHIKV infection. From this subgroup, 295 (53.8%) were positive for CHIKV IgG or IgM, and thus fulfilled the WHO criteria for confirmed CHIKV infections, of which 65 were HLA typing. Most frequent HLA-A alleles in the patients’ group were A*02 (n: 25;38.5%), A*24 (n: 21; 32.3%), and A*68 (n: 10; 15.4%), being the latter the only allele associated with CHIKV infection (p=0.005; OR: 8.90, CI:1.88- 42.13) while HLA A*29 was a protective factor for CHIKV infection (p=0.002; OR: 0.10, CI:0.02-0.44). HLA-B most frequent allele in CHIKV infected patients was B*35 in 47.7% (n: 31) with significant association (p=0.03; OR: 2.01, CI: 1.06-3.86). HLA-DRB1*04 (p=<0.001 OR:5.70, CI;1.95-16.59). DRB1*13 (p=0.004; OR: 3.75, CI: 1.50-9.39) and DRB1*01 (p= 0.001 OR: 5.70 CI; 1.95-16.59) was also found to be associated with CHIKV infection. HLA DRB1*04 was associated with face (p=0.02 OR: 3.20, CI; 1.11-9.15) and abdomen rash (p=0.007 OR: 4.33 CI;1.45–12.88).
Conclusions: This is the first study that evaluates the relation between HLA, CHIKV infection and the development of signs and symptoms. HLA type I and type II alleles are associated with CHIKV infection, and specifically an HLA type II allele with dermatological symptoms. Our results suggest the need of further research and set a path for future investigation on genes outside the HLA system to help elucidate the pathophysiology of the CHIKV infection as well as its interaction with its host.
A LATIN AMERICAN CARDIO-RHEUMATOLOGY CLINIC FOR PRIMARY PREVENTION OF CARDIOVASCULAR DISEASES
Dionicio Ángel Galarza Delgado1, José Ramón Aspin López2, Iris Jazmín Calunga Pedraza1, Ana Laura De León Ibarra1, Mayra Alejandra Reyes Soto1, Alejandra Pérez Villar1, Itzel Zarate Covina Salinas2, and Paola Fernanda Frausto Lerma1. 1Rheumatology Service, University Hospital, Dr. José Eleuterio González, UANL, Monterrey, México, 2Cardiology Service, University Hospital, Dr. José Eleuterio González, UANL, Monterrey, México.
Objective: Cardiovascular disease (CVD) is the most important comorbidity in rheumatic diseases. This has led to the development of Cardio-Rheumatology Clinics. Objective: describe the population characteristics and prevalence of primary prophylaxis of a cohort of patients attending the first Latin American Preventive Clinic since 2014, located in the University Hospital "Dr. Jose Eleuterio Gonzalez" in Monterrey, Mexico.
Methods: Cross sectional study. Rheumatoid Arthritis (RA) patients 40-75 years that fulfilled ACR/EULAR2010 and Psoriatic Arthritis (PsA) Caspar 2006 criteria with no CVD and no overlap syndromes were recruited from August 2014-December 2019. Each patient was evaluated by a rheumatologist on CVD assessment. Following the algorithms, patients who had high risk initiated primary prophylaxis and patients with moderate risk were re-stratified with carotid doppler of both arteries performed by a radiologist. Frequencies, mean (±SD) and medians were used.
Results: A total of 539 patients were included. Baseline characteristics are shown in Table 1. 64 RA patients were high risk classified using calculators. The other 31 patients with onset of primary prophylaxis were intermediate risk and reclassified to high risk using carotid doppler. CVD events occurred in RA, myocardial infarction in 8 (1.8), 2 (0.4) strokes and 1 stable angina. No CVD events in PsA were reported.
Conclusions: Among the patients who were referred to cardiovascular risk stratification, 121 (49.77%) needed preventive treatment with statins. These data demonstrate that there is a considerable increase in CVD risk in patients with rheumatic diseases, highlighting the importance of multidisciplinary work and prevention through the establishment of Cardio-Rheumatology Clinics.
LIVING WITH RHEUMATIC DISEASES: THE BRAZILIAN PATIENT’S PERSPECTIVE
Wanda Heloísa Ferreira1, Nilma Rodrigues de Oliveira2, Gladis Lima3, Iara Kobielski4, Mateus Rodrigues Alves5, and Mayari Eika Ishimura6. 1Instituto GRUPARJ-Petrópolis, Petrópolis, Brazil, 2ARUR, Uberlândia, Brazil, 3Psoríase Brasil, Porto Alegre, Brazil, 4GRUPAL, Porto Alegre, Brazil, 5Former UCB Biopharma employee, São Paulo, Brazil, 6UCB Biopharma, São Paulo, Brazil.
Background: The patient´s journey includes all experiences that a person goes through since the identification of the first symptoms of a disease. Therefore, it is crucial to understand this journey and to generate awareness that can positively impact the life of those patients who live with chronic inflammatory autoimmune diseases.
Objective: This study aimed to understand the different variables in the journey of people living with rheumatic disease in Brazil, as well as its association, and its impact on different areas of the patient's life.
Methods: Data were extracted from a survey containing 58 questions. It was available online for public participation. The association of qualitative variables was calculated through the Chi-square test. The null hypothesis was that the variables were not associated. To determine the strength of the association between variables, Cramer's coefficient was used. Analysis was performed on R software.
Results: Most of the 1223 participants were between the ages of 18 and 54 years. 38.72% were working, while 32.34% declared being retired or on sick leave. About 60% of the attendees have taken more than a year to be seen by a rheumatologist and 48.08% received their diagnose after at least one year of the first symptoms. More than half of the participants classified their disease activity as moderate or high, did not have access to another health care provider other than the rheumatologist, and reported no involvement with patients’ associations. While the majority considered themselves knowledgeable about their disease and treatment, the topic of family planning is still an issue to be addressed. Half of the women had an unplanned pregnancy (50%, n=71) and only a minority had discussed with their rheumatologist a treatment plan compatible with pregnancy (16.2%,n=23) or with breastfeeding (25.8%,n=31). Analysis of associations indicated that the type of treatment was associated with arthritis´ impact on daily activities (cc=0.478/p=0.001604), side effects (cc=0.5/p=0.00222), and satisfaction with treatment (cc=0.473/p=0.005009). Most participants considered that their arthritis had completely impacted their daily activities in the last month, regardless of their treatment. However, in the patients’ group treated with immunobiological drugs, there was a lower proportion of low satisfaction with treatment while a higher percentage of patients reported no side effects when compared to analgesics, non-steroidal anti-inflammatory drugs, corticoids, and synthetic Disease-Modifying Antirheumatic Drugs.
Conclusion: This work indicates opportunities for improving the patient’s quality of life and illustrates the complexity of the patient journey who lives with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis.
ASSOCIATION BETWEEN C -REACTIVE PROTEIN AND NEUTROPHILS / LYMPHOCYTES RATIO WITH THE FIVE SCORE FACTOR IN TREATMENT NÄIVE ANCA ASSOCIATED VASCULITIS PATIENTS
Pedro Arbey Quevedo Mayorga1, Paola Andrea Perez Benjumea1. 1Hospital Universitario Clínica San Rafael, Bogotá D.C, Colombia.
Introduction: Systemic vasculitis is a heterogeneous group of autoimmune diseases characterized by inflammation of the blood vessel wall as a result of activated proinflammatory cytokines in response to the presence of autoantibodies (ANCA) resulting in injury and tissue necrosis. The Five factor Score is an instrument that allows predicting five-year mortality according to the presence of specific clinical-demographic markers.
Objective: Establish the association between CRP and neutrophil/lymphocyte ratio with the Five Factor Score (FFS) as prognostic markers in patients with treatment naive ANCA vasculitis.
Materials and methods: Cross-sectional study. We included patients older than 18 years with diagnosis of ANCA associated vasculitis (ACR 90 classification criteria and Chapel Hill 2012) treatment naïve, being cared for at the San Rafael Clinic University Hospital in the last five years. Patients with infection, hematological disorder, and other connective tissue diseases were excluded. The information was obtained from medical records and registered as demographic, clinical and serological variables. The correlation analysis was performed with Spearman correlation coefficient (rho). The multivariate analysis by cluster analysis and principal components analysis (PCA). ANOVA analysis was applied for mean difference. A p value of < 0.05 was considered significant. R Study version 3.5.2 was used for statistical analysis.
Results: 37 patients were included, of which 56.67% were women. The mean age was 55 years (+/- 14.9). The ANCA associated vasculitis more frequently found was granulomatosis with polyangiitis (59.4%) followed by microscopic polyangitis (37.8%). The mean of N/L ratio was 6.87 (+/- 5.98), FFS was 1.43 (+/- 0.92), CRP 77.7 (+/- 74.4) and BVAS 10.62 (+/- 6.52). There was no correlation between FFS and R N/L (rho = -0.048 p = 0.77), but we found a positive correlation between CRP and R N/L (rho = 0.56 p = 0.0005). With regard to activity as assessed with the BVAS, a positive correlation was evidenced between CRP and BVAS (rho = 0.53 p = 0.0006) but not with R N/L and BVAS (rho = -0.05 p = 0.77). In the cluster analysis, a quality of 0.83 was demonstrated for 3 groups. In the analysis of variance no association was observed between FFS and R N / L (F = 0.023 p = 0.88).
Conclusions: Serological variables and the FFS do not show a significant correlation, however when examining this index with other serological markers, we found a significant correlation suggesting than alternative low cost markers may be useful in the evaluation of the systemic inflammatory response.
HEMATOMA IN THE PSOAS MUSCLE AS A MANIFESTATION OF HEMOPHILIA ACQUIRED IN LATE-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: A CASE REPORT
Cristian Camilo Guzman Gualteros1, Pedro Arbey Quevedo Mayorga1, Jhon Fredy Buitrago1, and Viviana Lopez Ramirez1. 1Hospital Universitario Clínica San Rafael, Bogotá, Colombia.
Case Report: 78-year-old male patient with asymmetric edema of the right lower limb, insidious onset associated with limitation for walking, no history of trauma or medication use. Other symptoms, he referred photosensitivity, oral ulcers, xerostomia, xerophthalmia and arthralgias. No medical history of relevance. On physical examination he had normal vital signs, conjunctival hypochromia, presence of an ecchymotic lesion of the anterior side of the right non-painful arm and pain at flexion of the left hip, no synovitis. Laboratory tests performed revealed anemia of normal volumes, without thrombocytopenia or leukopenia. The partial thromboplastin time (PTT) was prolonged in 97.7 Sec (normal: 26 - 32 Sec), with prothrombin time (PT) in 12.5 Sec (Normal: 10.4 - 13 Sec) cross-PTT study and Rosner adjustment index test in non-incubated tubes detected an abnormal value by raising the probability of a specific inhibitor; later the study was complemented with factor VIII levels: 0.4% (50 - 150), and the measurement of factor VIII inhibitors was performed with positive results (18 Bethesda Units). Due to the limitation of the lower limb, computed tomography of the pelvis was performed, showing hematoma in the left psoas muscle. Given the suspicion of secondary etiology of hemophilia, an autoimmunity profile with positivity for 1/640 positive antinuclear antibodies, anti-Ro/SSA (-), anti La/SSB (-), anti Sm (-), anti RNP (-), and anti-DNAds (-) without complement consumption was performed. Other etiologies such as paraneoplastic syndromes and hematologic malignancies were ruled out; and it was considered that the patient fulfilled SLE classification criteria (SLICC / ACR 2012); immunosuppressive treatment with steroids was indicated at a high dose (1mg / k / day) plus azathioprine 50mg every 12 hours plus activated prothrombin complex at a dose of 90mg / kg dose; Factor VIII inhibitor levels control was performed with subsequent decrease to 8.3 units Bethesda / ml after 3 weeks of treatment.
Conclusion: Acquired hemophilia is an unusual hematological expression of rheumatic disease; due to its variable severity, it must be considered as a differential diagnosis in elderly patient with hemorrhagic disorders and associated autoimmunity.
DETECTION AND INTERVENTION OF RHEUMATIC DISEASES IN INDIGENOUS COMMUNITIES IN CHIAPAS
Leticia Santoyo Fexas1, C. Mario Alberto Garza Elizondo1, Cesar Vidal Elizondo Solis1, Martha Mariana Castañeda Martinez1, Andrea Moreno Salinas1, Ingris Peláez Ballestas2, and Dionicio Ángel Galarza Delgado1. 1Hospital Universitario "José Eleuterio González", Monterrey, México, 2Hospital General de México "Dr. Eduardo Liceaga", México, México.
Background: Indigenous populations have a higher prevalence of rheumatic diseases than the general population; the process of seeking medical attention in indigenous communities is usually very long, due to this these patients are predisposed to late diagnosis and worse prognosis and outcomes.
Community-oriented program for the control of rheumatic diseases (COPCORD) is a program aimed at obtaining reliable epidemiological information from the community for the control of rheumatic diseases.
Objective: Estimate the prevalence of musculoskeletal disorders, rheumatic diseases and other associated diseases using COPCORD methodology, as well as to evaluate quality of life with EuroQ5d.
Material and methods: Design: Community-based-cross-sectional epidemiological study was conducted in the communities of Chenalhó, Chiapas, México in which all transculturally valid screening questionnaires (COPCORD) and quality of life (EuroQ5d) were applied house by house by health professionals with the help of translators. Positive COPCORD individuals were evaluated by a rheumatologist for diagnosis and treatment.
Population: patients over 18 years, who met the criteria for indigenous designated by the National Commission for the Development of Indigenous Populations of Mexico.
An informed consent was signed in their dialect, Tzotzil and Spanish.
A descriptive analysis of variables was performed.
Results: A census of the study population was conducted, where 453 inhabitants were registered, of which 209 were adults, 126 fulfilled the inclusion criteria, 116 (90.4%) reported painful joint or soft tissue/musculoskeletal pain in the last 7 days, 12 (9.5%) were diagnosed with rheumatoid arthritis, 15 (11.9%) with osteoarthritis, 18 (14.2%) with regional appendicular pain syndrome, 18 (14.2%) with low back pain, 51 (40.5%) with nonspecific musculoskeletal disorders.
The quality of life is reported in graphic 1.
Conclusions: The prevalence of musculoskeletal disorders is remarkably high in this population compared to the reported in the general population (90.4% vs 25%). Likewise, the prevalence of rheumatic diseases was 35.7% being higher than reported in indigenous communities of Guatemala (8.4%) and Chihuahua, Mexico (10.5%). These types of epidemiological studies are essential to create a plan to support indigenous communities and achieve better management of health problems.
This was the phase one of a larger study; now we are studying the process of seeking medical care, and after that to implement a program of care with cultural sensitivity.
EPIDEMIOLOGICAL CHARACTERISTICS OF SARCOIDOSIS PATIENTS IN A REFERRAL HOSPITAL OF THE CITY OF CALI, COLOMBIA
Germán Eduardo Puerta Sarmiento1,2, Mario Alejandro Bautista Vargas1,2, Gabriel David Pinilla Monsalve1,2, Juan David Marin Escobar2, and David Alejandro Aguirre Valencia1. 1Hospital Universitario Fundación Valle del Lili, Cali, Colombia, 2Universidad ICESI, Cali, Colombia.
Objetives: The objective of this work is to provide data on the epidemiological and clinical characteristics of sarcoidosis in a population of diverse ethnicities with a high level of miscegenation.
Methods: Clinical records were taken between January 2011 and July 2019 of patients diagnosed with sarcoidosis at the Fundación Valle del Lili Universitarian Hospital. Demographic variables, initial symptoms of disease presentation, involvement of other systems, paraclinical at the time of diagnosis were analyzed, including in most cases angiotensin-converting enzyme levels. In addition, the findings in pulmonary CT were analyzed, as well as the findings in the lung or other organ biopsied. Finally, a description was made of the treatment received with which initial control of the symptoms was achieved.
Conclusions: Sarcoidosis is more common in Mestizos and occurs earlier in men, high ACE levels do not relate to extrapulmonary involvement, serum phosphorus-calcium profile alteration was not useful. ANAs test positivity could be a diagnostic exclusion factor.
REAL WORLD EFFECTIVENESS OF SECUKINUMAB IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: FINDINGS FROM A RECENT CROSS-SECTIONAL SURVEY OF RHEUMATOLOGISTS AND PATIENTS IN EUROPE
Uta Kiltz1, Elizabeth Holdsworth2, Haijun Tian3, Nicola Booth2, Papa Anthony2, Niraj Modi4, Dorothy Keininger5, and Philip Conaghan6. 1Rheumazentrum Ruhrgebiet, Herne, and Ruhr-University Bochum, Germany, 2Adelphi Real World, Manchester, UK, 3Novartis Pharmaceuticals Corporation, East Hanover, USA, 4Novartis Healthcare Pvt Ltd, Hyderabad, India, 5Novartis Pharma AG, Basel, Switzerland, 6University of Leeds, UK.
Objective: Secukinumab has demonstrated clinical benefits in axSpA patients in clinical trials. This study assessed effectiveness of secukinumab in axSpA in a real-world setting.
Methods: This was a cross-sectional survey of rheumatologists and patients in France, Germany, Italy, Spain, and UK. Data were collected online from June-December 2018 via physician-completed patient record forms. Patients receiving any treatment for axSpA were included in the survey (n=1392). Patients receiving secukinumab >4 months were included in this analysis. Patients reported current satisfaction with secukinumab treatment, quality of life, work, and functioning measures at current consultation (EQ5D, WPAI, ASAS HI). Physicians reported patient demographic and disease characteristics, current symptoms, concomitant and previous treatments, time since diagnosis, and physician satisfaction with secukinumab. Physicians also reported overall disease severity (mild/moderate/severe), pain (1-10 scale), global VAS score (0-100 scale), and BASDAI score for two time points – at the initiation of secukinumab, and at the time of data collection (current consultation). Data were analysed descriptively.
Results: 359 axSpA patients were receiving secukinumab >4 months at their current consultation. Patient mean age was 45.4 years, with 25% female, 67% working full time, and a mean BMI of 25.7. On average, patients were diagnosed with axSpA 7.1 years before, had received secukinumab for 10.6 months, and for 53% of patient secukinumab was their 1st advanced therapy (specifically bDMARDs), 30% their 2nd, 17% their 3rd or more. 15% of patients were also receiving a csDMARD concurrently. 9% of patients had enthesitis, and 20% had spinal fusion. Patients reported a mean EQ5D utility score of 0.83, mean WPAI overall work impairment of 27.4%, and mean ASAS HI score of 5.4 at their current consultation. 83% of patients and 92% of physicians reported being satisfied with secukinumab. Between initiation of treatment and current consultation, reduction in BASDAI score (at initiation 6.2 vs at current consultation 2.9), pain score (7.3 vs 3.1), and physician (56.2 vs 23.7) and patient (63.4 vs 26.5) global VAS score were observed. 50.6% of patients achieved a 50% reduction in BASDAI score. Proportion of patients with moderate and severe disease severity decreased at the current consultation (mild: 66.6%; moderate: 30.9%, severe: 2.5%) vs at the initiation of secukinumab treatment (mild: 1.9%; moderate: 49.8%, severe: 47.6%).
Conclusions: This study provides insight into secukinumab effectiveness in axSpA in a real-world clinical setting. Significant improvements were seen across all outcomes highlighting a sustained response to secukinumab.
TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND CO-OCCURRENCE OF DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF PHASE 3 AND PHASE 3B/4 CLINICAL TRIALS
Gustavo Citera1, Rakesh Jain2, Fedra Irazoque3, Renato Guzman4, Hugo Madariaga5, David Gruben6, Lisy Wang6, Lori Stockert7, Ming-Ann Hsu6, Karina Santana8, Abbas Ebrahim7, and Dario Ponce de Leon9. 1Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 2Texas Tech University School of Medicine, El Paso, USA, 3Hospital Angeles Mocel, San Miguel, México, 4Fundación Universitaria Juan N. Corpas e IDEARG, Bogotá, Colombia, 5Clínica del Sur, Arequipa, Peru, 6Pfizer Inc, Groton, USA, 7Pfizer Inc, Collegeville, USA, 8Pfizer Inc, Ciudad de México, México, 9Pfizer Inc, Lima, Perú.
Objectives: Depression and anxiety are common in patients with rheumatoid arthritis (RA). The 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS)≤38 has been used to identify probable major depressive disorder and/or probable generalized anxiety disorder (pMDD/pGAD) in patients with RA.1 Tofacitinib is an oral JAK inhibitor for the treatment of RA. We assessed pMDD/pGAD prevalence by SF-36 MCS≤38 status in tofacitinib clinical trials for RA, and efficacy by baseline pMDD/pGAD status.
Methods: This post hoc analysis pooled data from five Phase 3 trials and one Phase 3b/4 trial, and included patients receiving tofacitinib 5 or 10mg twice daily (BID), adalimumab 40mg every other week (ADA), or placebo, with non-missing baseline SF-36 MCS. Demographics/baseline characteristics were reported by baseline pMDD/pGAD status (SF-36 MCS ≤38, presence; >38, absence). At Months (M)3/6/9/12, SF-36 MCS change from baseline (Δ) was estimated by modeling pooled data and percentage of patients with pMDD/pGAD reported. Efficacy endpoints (American College of Rheumatology [ACR]20/50/70 response rates; Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)]<2.6 rates; ΔHealth Assessment Questionnaire-Disability Index [HAQ DI]) were estimated at M3/6/12 by linear models, comparing tofacitinib-treated patients by baseline pMDD/pGAD status.
Results: Baseline pMDD/pGAD were reported in 44.5% (tofacitinib 5mg BID), 39.8% (tofacitinib 10mg BID), 45.4% (ADA), and 39.1% (placebo) of patients. At baseline, higher C-reactive protein levels and worse disability, fatigue, pain, and sleep were reported in patients with vs without pMDD/pGAD. A numerically, and sometimes significantly, greater increase in SF-36 MCS was reported with tofacitinib vs placebo/ADA (ADA through M12). The proportion of patients with baseline pMDD/pGAD who continued to have pMDD/pGAD at M3/6/9/12 was generally lower with tofacitinib vs placebo/ADA and had reduced from baseline by 61.9–63.7% at M12. Efficacy at M3/6/12 was generally similar with tofacitinib 5 and 10mg BID, irrespective of baseline pMDD/pGAD status.
Conclusions: Around 40% of patients with RA had baseline pMDD/pGAD identified by SF-36 MCS≤38. Improvement in SF-36 MCS was greater in patients receiving tofacitinib vs placebo/ADA. In tofacitinib-treated patients, the proportion with pMDD/pGAD reduced by ~60% at M12. Tofacitinib efficacy was similar in those with/without baseline pMDD/pGAD. Future research using a gold-standard psychiatric interview is required to validate SF-36 MCS≤38 in the identification of pMDD/pGAD.
Reference: 1. Matcham F et al. BMC Musculoskelet Disord 2016; 17: 224.
Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.
COMPARISON OF DIFFERENT REMISSION INDICES IN PATIENTS WITH PSORIATIC ARTHRITIS: A POST HOC ANALYSIS OF DATA FROM PHASE 3 TOFACITINIB STUDIES
Emilce E. Schneeberger1, Gustavo Citera1, Peter Nash2, Josef S. Smolen3, Philip Mease4, Enrique R. Soriano5, Claudia Helling6, Annette Szumski7, Rajiv Mundayat8, Daniela Graham9, and Dario Ponce de Leon10. 1Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 2Department of Medicine, Griffith University, Brisbane, Australia, 3Medical University of Vienna, Austria, 4Swedish Medical Center and University of Washington, Seattle, USA, 5Hospital Italiano de Buenos Aires, Buenos Aires, Argentina, 6Pfizer Inc, Buenos Aires, Argentina, 7Pfizer Inc, Collegeville, USA, 8Pfizer Inc, New York, USA, 9Pfizer Inc, Groton, USA, 10Pfizer Inc, Lima, Perú.
Objectives: The Disease Activity Index in Psoriatic Arthritis (DAPSA) and psoriatic arthritis (PsA) minimal disease activity (MDA) are recommended to assess remission and low disease activity (LDA).1 Tofacitinib is an oral JAK inhibitor for the treatment of PsA. We compared DAPSA LDA with MDA, and DAPSA remission with very low disease activity (VLDA) and DAS28-3(CRP) remission, in patients with PsA receiving tofacitinib.
Methods: Data were pooled post hoc from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) for patients receiving tofacitinib 5 (n=237) or 10mg (n=236) twice daily (BID) or placebo (n=236). DAPSA was determined by summing: swollen joint count (SJC66); tender/painful joint count (TJC68); Patient Global Assessment of Arthritis (PtGA; visual analog scale [VAS]); patient-assessed pain (VAS); and CRP. MDA or VLDA was defined as ≥5 (MDA) or ≥7 (VLDA) of the following criteria: TJC68 ≤1; SJC66 ≤1; Psoriasis Activity and Severity Index ≤1 or body surface area ≤3%; Pain (VAS) ≤15; PtGA (VAS) ≤20; HAQ-DI ≤0.5; Leeds Enthesitis Index ≤1. Logistic regression modelled demographic and baseline characteristics as predictors of DAPSA scores at Month (M)3. DAPSA LDA (≤14), MDA, DAPSA remission (≤4), VLDA, and DAS28-3(CRP) remission (<2.6) rates were compared at M1, M3, and M6 for tofacitinib 5mg BID, and at M6 for tofacitinib 5/10mg BID. A Kappa test evaluated agreement between disease activity indices at M6. The percentage of tofacitinib-treated patients achieving MDA and VLDA at M6 was stratified by achievement of DAPSA LDA or remission.
Results: Older patients receiving tofacitinib, and tofacitinib- or placebo-treated patients with higher baseline SJC66, TJC68, PtGA VAS, HAQ-DI, LEI and Pain VAS, were significantly (p<0.05) more likely to have higher DAPSA at M3. DAPSA LDA/remission, MDA, DAS28-3(CRP) remission, and VLDA rates generally increased from M1 to M6 in both tofacitinib dose groups. At M6, most tofacitinib-treated patients with MDA, and all with VLDA, were also in DAPSA remission or LDA. There was ≥moderate agreement (defined as Kappa values 0.41−0.60) between DAPSA LDA/remission and MDA, and DAPSA remission and VLDA.
Conclusion: Remission and LDA rates generally increased over time in patients with PsA receiving tofacitinib. DAPSA LDA and remission showed ≥moderate agreement with MDA and VLDA, respectively. DAPSA and MDA are useful tools to measure PsA disease activity.
Reference: 1. Smolen JS et al. Ann Rheum Dis 2018; 77:3-17.
Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.
DIFFERENTIAL CHARACTERISTICS BETWEEN ARTHRITIS PATIENTS UNDER STANDAR VS OPTIMIZED DOSE BIOLOGICAL TREATMENT
Simón Ángel Sánchez-Fernández1, Leticia del Olmo Perez2, and Ángel García-Aparicio3. 1Hospital La Mancha Centro, Alcazar De San Juan, España, 2Hospital Nuestra Señora del Prado, Talavera de la Reina, España, 3Hospital Virgen de la Salud, Toledo, España.
Purpose: To determine whether inflammatory joint disease patients receiving biological therapy (BT) present differences in various sociodemographic, disease features or treatment characteristics, regarding the use of BT at standard and optimized doses and/or frequencies.
Methods: Patients diagnosed with rheumatoid arthritis (RA), inflammatory spondyloarthropathy (SpA), psoriatic arthropathy (PsA) and juvenile idiopathic arthritis (JIA) and who received BT were included. Sociodemographic characteristics: age, sex, smoking habit and body mass index (BMI); disease features: diagnosis, HLA B27, RF or ACPA; and treatment: current BT, previous BT, time from diagnosis until the first BT and treatment without DMARD were obtained. We registered if BT was tried to be optimized and if it could be maintained, as well as the dose and frequency of administration.
Results: We included 147 patients (61.2% women and 38.8% men) with a mean age of 53.8 years. The mean BMI was 28.4, 54.5% were active smokers or ex-smokers and 45.5% were non-smokers. From the RA patients, 87.7% were RF and /or ACPA positive and from the SpA patients 73.3% were HLA B27 positive.
BT was given without DMARD to 32.7% of all patients and the mean time from the diagnosis to the first BT was 90.5 months; 32% had received at least one previous BT [mean number of previous BT of 1.5 (0.9; 1-5)]. The optimization attempt was made in 81 patients (55.1%) and it was maintained in 54 (36.7%).
Comparing patients with BT at standard versus optimized doses, no significant differences were found in most of the sociodemographic, disease or treatment characteristics examined. There were significant differences in BMI (29.3 vs 26.8, p = 0.007), having or not previous BT (p <0.001) and number of previous BT (1.7 vs 1.1, p <0.001). In multivariate analysis we found an OR = 1.13 (95% CI: 1.04-1.22), p = 0.004 for the BMI and an OR = 6.98 (95% CI: 2.6-18.7), p <0.001 to have received or not prior BT.
Comparing patients attempted to optimize BT without success with those in which optimization was maintained, significant differences were found only in BMI (29.5 vs 26.9, p = 0.047).
Conclusion: Among our patients with inflammatory arthropathy who receive standard vs. optimized BT there are differences regarding the BMI and previous biological treatment received.
The risk of non-optimization increases by 1.13 times for each point increased of the BMI, and up almost 7 times in the case of having received previous BT.
SECUKINUMAB PROVIDES SUSTAINED IMPROVEMENT OF ENTHESITIS IN ANKYLOSING SPONDYLITIS PATIENTS: A POOLED ANALYSIS OF FOUR PIVOTAL PHASE 3 TRIALS
Atul Deodhar1, Georg Schett2, Xenofon Baraliakos3, Filip Van den Bosch4, Lianne Gensler5, Mikkel Østergaard6, Shital Agawane7, Ayan Gupta7, Shephard Mpofu8, Todd Fox8, Adam Winseck9, Brian Porter9, and Abhijit Shete8. 1Oregon Health & Science University, Portland, United States of America, 2Department of Internal Medicine, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany, 3Rheumazentrum Ruhrgebiet Herne, and Ruhr University Bochum, Herne, Germany, 4Ghent University Hospital, Belgium, 5University of California, San Francisco, United States of America, 6Copenhagen Center for Arthritis Research, University of Copenhagen, Copenhagen, Denmark, 7Novartis Healthcare Pvt Ltd, Hyderabad, India, 8Novartis Pharma AG, Basel, Switzerland, 9Novartis Pharmaceuticals Corporation, East Hanover, United States of America.
Objectives: To evaluate the effect of secukinumab (SEC) on axial and peripheral enthesitis in ankylosing spondylitis (AS) patients (pts) with baseline enthesitis (BLE) across all Maastricht Ankylosing Spondylitis Enthesitis Score-(MASES) sites (N=13), axial sites [N=11; 13 MASES minus Achilles tendons (AT); AxS], peripheral sites (N=6; AT + lateral condyles of humerus/femur; PS), and the AT (N=2) at Weeks (Wks) 16 and 52.
Material and Methods: This post hoc analysis pooled data across 4 SEC studies (MEASURE 1-4) from pts originally randomized to SEC 150mg, 300mg (MEASURE 3 only), or placebo (PBO) with BLE (MASES >0). Evaluations include mean change from BL in MASES, complete resolution (CR; MASES=0) and improvement from BL in MASES score of ≥5 counts.
Results: Overall, 355 (70.4%), 58 (76.3%), and 280 (72%) pts had BLE in 150mg, 300mg and PBO groups, respectively. At Wk16, mean change from BL for overall MASES and AxS was greater for SEC 150/300mg vs PBO. At Wk16, a higher proportion of pts treated with SEC 150/300mg vs PBO achieved CR of enthesitis based on overall MASES and at AxS. A higher proportion of SEC vs PBO-treated pts achieved a higher threshold of improvement (≥5 counts) in overall MASES at Wk16. Further improvements were observed for all endpoints at Wk52 (Table).
Conclusion: SEC 150mg and 300mg were associated with higher mean change in MASES and complete resolution of enthesitis at overall MASES and AxS compared to PBO in AS pts at Wk16, which further increased through Wk52.
OUTCOMES OF CHIKUNGUNYA VIRUS INFECTION IN PATIENTS WITH PRE-ESTABLISHED RHEUMATOID ARTHRITIS
Mario Bautista Vargas1, Germán Puerta Sarmiento1, Nicolás Salazar Otoya1, and Carlos Cañas Dávila1. 1Fundación Valle Del Lili, Cali, Colombia.
Background: Chikungunya virus (CHIKV) is an arbovirus that caused a pandemic with cases reported in Colombia, mainly between 2014 and 2015, with an incidence of 1356 cases per 100,000 inhabitants. Around 150 cases were treated at Fundación Valle del Lili Hospital, Cali, Southwest Colombia; six patients were found to have a previous diagnosis of Rheumatoid Arthritis (RA) who were in clinical remission at that time. Outcomes of CHIKV infection in pre-established RA are not reported in the medical literature. We present a case series of this condition treated in our hospital.
Aim: The aim of this study is to describe both clinical manifestations and treatment required by patients with RA in clinical remission and intercurrent CHIKV infection.
Methods: Medical records of patients with RA who had intercurrent CHIKV infection were examined. Clinical outcomes were measured with the DAS28 score before, during and after infection. Additionally, we describe the treatment options needed in those patients to achieve disease control.
Results: Five women and one man were found, with a mean age of 66 years (SD 11.9), who had been receiving low doses of glucocorticoids (GC) (mean dose of prednisolone: 4.2 mg each day, SD 1.3). Three patients received Methotrexate, two received Etanercept before CHIKV infection, with a mean DAS28 of 2.9 (SD 0.5) by the last control visit. At the time of CHIKV infection, in addition to the constitutional symptoms, they presented a mean DAS28 of 4.0 (SD 0.4), requiring more than double their usual dose of GC (mean dose of prednisolone: 8.8mg each day, SD 2.6). Due to the poor clinical response, one patient required a change from Etanercept to Adalimumab and three others started Rituximab, Tocilizumab and Tofacitinib as a de novo second-line medication. The table summarizes the findings.
Conclusions: A case series of patients with RA in clinical remission who presented acute CHIKV infection, are reported. Those patients developed exacerbation of their underlying disease, with an important difficulty to achieve control of joint inflammation. An increase in the doses of GC and switch or induction to the use of second-line medications (anti-TNF, anti-CD20 or Janus Kinase Inhibitor) was required.
NEURO BEHÇET’S MIMICKING PONTINE GLIOMA: A CASE REPORT
Dijo Joseph1,3, Ritwik Bhatia2,3, and Larry Young3. 1Jackson Memorial Hospital/University of Miami Internal Medicine Residency Program, Miami, United States, 2Jackson Memorial Hospital/University of Miami Neurology Residency Program, Miami, United States, 3Bruce W. Carter Miami Veterans Association, Miami, United States.
Introduction: Behçet's Syndrome (BS) is a systemic inflammatory disorder that classically causes multiple oral ulcers, genital ulcers, and ocular lesions.
Less than 10% of patients with BS can also develop Neuro Behçet's (NB), which has a particular predilection for young adult males and individuals of Mediterranean heritage. Patients can develop headache, behavioral changes, and focal neurological symptoms corresponding to lesions most commonly in the brainstem, diencephalon, and basal ganglia. We present a case of a Peruvian-Italian male who was thought to have a pontine glioma but was subsequently diagnosed with NB.
Case Report: A 36- year old Peruvian-Italian male with a past medical history of migraines presented with six months of worsening headaches associated with transient diplopia and blurred vision. Patient was hospitalized and additionally developed acute onset confusion and seizures, prompting an MRI brain which revealed lesion concerning for pontine glioma.
Patient was then transferred to our hospital, and after having been given intravenous steroids, reported improvement of headache and cognitive symptoms, but had persistent visual disturbances. Neurological exam was significant for diplopia, decreased sensation on the left side of his face, and gait instability. Oral mucosa had multiple ulcerated lesions and patient revealed a three-year history of recurrent oral and genital ulcers. There were no active genital lesions, synovitis, or skin rashes.
CSF studies demonstrated WBC 1, glucose 70, and protein 27. No evidence of malignancy was noted on pathological examination of CSF. Autoimmune, paraneoplastic, and infectious labs were negative.
Repeat MRI brain showed a decrease in size of the left pontine lesion, with no evidence of enhancement.
Fluorescein angiography demonstrated retinal vasculitis. Pathergy skin test was negative for any pustules.
Patient met international criteria for NB, and was initiated on pulse dose methylprednisolone, exhibiting further improvement in symptoms.
He was discharged on prednisone 50 mg daily and, after complete resolution of his symptoms, was started on adalimumab and a steroid taper.
Discussion: This case illustrates a presentation of NB that was initially diagnosed as pontine glioma. Integration of clinical history, including demographics, associated signs and symptoms, as well as thorough physical examination can raise clinical suspicion for NB in the setting of an indeterminate CNS lesion. Given the rarity of Behçet's syndrome in the western hemisphere, it is a diagnostic challenge that requires an understanding of the disease in order to guide efficient, expedited treatment to prevent unnecessary testing, treatment, and life-threatening neurological consequences.
ARE THERE ANY IDENTIFIABLE TRIGGERS IN POLYMYALGIA RHEUMATICA? A MATCHED-CONTROL STUDY
Mayra Alejandra Tobar Jaramillo1, Victor Santos Andrade1, Marina Scolnik1, John Fredy Jaramillo Gallego1, Luciano Lo Giudice1, Gelsomina Alle1, Dra Valeria Scaglioni1, and Enrique Soriano1. 1Hospital Italiano De Buenos Aires, Ciudad autónoma de Buenos Aires, Argentina.
Background: As with many other rheumatologic diseases, the pathogenesis of Polymyalgia Rheumatica (PMR) is not well understood. Genetic factors seem to play a role. Some studies have suggested a seasonal variation, indicating a possible infectious trigger; others have shown and association with statins’ initiation. Our objective was to compare PMR patients with matched controls in order to identify possible triggers in the year previous to PMR development.
Methods: PMR patients (fulfilling ACR 2012 criteria) belonging to a Health Management Organization (HMO) of a tertiary university hospital were matched 1:1 by gender and date of birth with controls belonging to the same HMO. Date of PMR diagnosis was considered as the index date for patients and their corresponding control. Electronic medical records were manually reviewed and data on infections, hospitalizations, surgeries, vaccines and starting of statins in the year previous to the index date were recorded for both PMR patients and controls and compared between them. For PMR patients, season where disease symptoms started was also examined.
Results: 169 PMR patients and 169 controls were included. 79.9 % were female. Age at PMR diagnosis was 79.5 years (SD 6.1). No differences were found between PMR patients and controls regarding infections, hospitalizations, vaccines, surgeries or statin initiation in the year previous to PMR diagnosis (table 1). PMR symptoms started in summer in 50 patients (29.6%, 95% CI: 23.1-36.9), in autumn in 50 (29.6%, 95% CI: 23.1-36.9), winter in 42 (24.8%, 95% CI: 18.9-31.9) and spring in 27 (15.9%, 95% CI: 11.1-22.4) (Table 2).
Conclusion: We did not find an identifiable trigger for the development of PMR when analyzing data from the year previous to diagnosis comparing to matched controls. No seasonal pattern was clearly seen.
INTERFERON LAMBDA 3/4 (IFNΛ3/4) RS12979860 POLYMORPHISMS ARE NOT ASSOCIATED WITH SUSCEPTIBILITY TO SYSTEMIC LUPUS ERYTHEMATOSUS, ALTHOUGH THEY ARE ASSOCIATED WITH OASL-1 EXPRESSION LEVELS IN MEXICAN PATIENTS
Yaneli Juárez-Vicuña1,2, Julia Peréz-Ramos3, Laura Adalid-Peralta4,5, Fausto Sánchez6, María del Carmen Ortiz-Segura7, Aline L. Martínez-Martínez8, Edgar Pichardo-Ontiveros9, Luis M. Amezcua-Guerra2, and Fausto Sánchez-Muñoz2. 1Programa de Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, Ciudad De México, México, 2Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México, 3Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, Ciudad de México, México, 4Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México, 5Unidad Periférica para el Estudio de Neuroinflamación en Patologías Neurológicas del Instituto de Investigaciones Biomédicas en el Instituto Nacional de Neurología y Neurocirugía, Ciudad de México, México, 6Departamento de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, Ciudad de México, México, 7Departamento de Investigación en Farmacología y Toxicología, Hospital Infantil de México Federico Gómez, Ciudad de México, México, 8Departamento de Reumatología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México, 9Departamento de Fisiología de la Nutrición, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
Background: Genetic factors are strongly associated with susceptibility to systemic lupus erythematosus (SLE) and contribute to the onset and progression of the disease. In particular, interferon lambda 3/4 (IFNλ3/4) rs12979860 single nucleotide polymorphism (SNP) are significantly associated with SLE susceptibility in Taiwanese. In addition, the expression of several interferon-stimulated genes (ISGs) is increased in SLE patients in parallel with the extent of disease activity.
Objectives: To investigate whether the rs12979860 SNP is associated with the presence of SLE in Mexican individuals, and to assess whether this SNP is associated with the expression of several ISGs.
Methods: We included patients with SLE according to the 1997 classification criteria of the American College of Rheumatology, as well as healthy blood donors without a family history of autoimmune diseases. DNA was extracted from whole blood using UltraClean DNA BloodSpin (MO BIO Laboratories, Carlsbad, CA, USA). Genotyping was performed using TaqMan probes by real-time PCR and allelic discrimination plots were constructed for rs12979860 IFNλ3/4 SNP using software of LightCycler 480 system (Roche). In parallel, peripheral blood mononuclear cells (PBMCs) were isolated from venous blood by centrifugation in Ficoll-Histopaque-1077 from SLE patients (n=78). We determined levels of mRNA levels of the ISGs OASL-1, MX1, OAS1, ISG15 and Ly6E using real- time RT-PCR.
Results: A total of 164 patients with SLE and 169 healthy blood donors were included in the study. The genotype and allelic frequencies of the rs12979860 polymorphism were similar between patients with SLE and controls. The distribution of rs12979860 SNP in SLE patients was as follows: 44 (27%) CC, 83 (51%) CT and 37 (23%) TT; meanwhile, among the healthy donors were as follows 43 (25%) CC, 89 (53%) CT and 37 (22%) TT. The rs12979860 SNP was associated neither with the susceptibility to SLE nor with the development of lupus nephritis. However, OASL-1 expression levels by PBMCs were significantly different between rs12979860 genotypes in SLE patients. Patients carrying CC genotype showed OASL-1 mRNA median levels significantly higher (0.282± 0.049) than patients with CT and TT genotypes (0.182± 0.025 and 0.172± 0.024 respectively; p<0.05). Meanwhile, no association was observed between the rs12979860 genotypes and the level expression of MX1, OAS1, ISG15 or Ly6E.
Conclusions: Our results suggest that rs12979860 polymorphism does not play a relevant role in susceptibility to SLE in Mexican individuals. Although IFNλ3/4 genotypes appear to be associated with the expression of the ISG OASL-1 by PBMCs from patients with SLE.
OCULAR CICATRICIAL PEMPHIGOID: IS IT AN UNDERDIAGNOSED DISEASE?
Andrea María Smichowski1, Victor Caputo, Cecilia Romeo, Estela Rivero, Natalia Morales, and Gustavo Casado. 1Hospital Militar Central 601, Caba, Argentina.
Introduction: Mucous Membrane Pemphigoid (MMP) is a chronic, multi-systemic autoimmune subepithelial blistering disease which predominantly affects the mucous membranes and may cause serious irreversible scarring. Isolated ocular involvement is known as Ocular Cicatricial Pemphigoid (OCP) and may lead to irreversible blindness if it is not treated early enough. The treatment involves the suppression of inflammation with systemic immunomodulatory drugs.
Objective: To examine the epidemiological and clinical data, as well as management and treatments established for patients with OCP in the Rheumatology Service of our Hospital.
Methods: Observational descriptive study of medical records data collected in patients with a diagnosis of OCP by conjunctival biopsy, referred from the Ophthalmology Service for the management of systemic immunosuppressive therapy from 2008 to 2019.
Results: The medical records of 27 patients diagnosed with OCP by biopsy were reviewed. Women predominated, 62.9% and the mean age at diagnosis was 65 years (SD 9.215). The average duration of disease was 4.3 years (SD 6.384) and the average time from the first symptoms to the diagnosis was 2.5 years (SD 2.17). No extraocular manifestations were observed. The average follow-up time was 25.6 months. 67% of the patients were diagnosed and referred overthe last 2 years. The majority presented Foster Stage I. Unilateral progression of stage was observed in only two patients. 18.5% (5 patients) had associated Sjogren's Syndrome. 4 of these 5 patients had to change the treatment. 40.7% showed erythrosedimentation greater than 20, 25.9% were C-reactive protein positive, and 33.3% had polyclonal hypergammaglobulinemia. In 29.6%, a history of cancer was recorded.
Regarding treatment, 1 patient underwent topical treatment with cyclosporine, 24 with methotrexate (88.8%), 2 with azathioprine, 1 with leflunomide, 4 with mycophenolate mofetil, 2 with cyclophosphamide, 1 with sirolimus and 3 with rituximab. The majority continues in monotherapy with methotrexate. Only 5 patients switched treatment and / or received combination of treatment. 4 patients are currently in remission without treatment. 37% presented mild adverse events, mostly gastrointestinal. No serious adverse events were recorded.
Conclusion: Epidemiological data coincide with previous publications. The association with Sjogren`s Syndrome worsens the prognosis.
Most of the patients were referred over the last two years due to the greater knowledge and suspicion of this pathology. This enables early treatment and better prognosis.
Early initiation of immunosuppressive therapy is essential. In our experience, methotrexate is an effective and safe first-line alternative and the treatment must be scaled according to the disease’s course
INHIBITION OF STRUCTURAL JOINT DAMAGE WITH UPADACITINIB AS MONOTHERAPY OR IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Charles G. Peterfy1, Mark C. Genovese2, In-Ho Song3, Alan Friedman3, Stephen Hall4, Eduardo Mysler5, Patrick Durez6, Xenofon Baraliakos7, Jeffrey V. Enejosa3, Tim Shaw3, Yihan Li3, Su Chen3, and Vibeke Strand2. 1Spire Sciences Inc., Kentfield, USA, 2Stanford University, Palo Alto, USA, 3AbbVie Inc., North Chicago, USA, 4Monash University, Cabrini Health and Emeritus Research, Malvern, Australia, 5Organización Médica de Investigación, Buenos Aires, Argentina, 6Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium, 7Herne and Ruhr-University, Bochum, Germany.
Background: Long-term prevention of structural joint damage is a key treatment goal in the management of RA1. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)-naïve RA patients (pts)2 and in combination with MTX in pts with inadequate response (IR) to MTX3.
Objective: To evaluate the progression of structural joint damage (radiographic) through Week 48 in pts with moderately to severely active RA treated with UPA monotherapy or in combination with MTX.
Methods: Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs), as previously described2,3. MTX-naïve pts were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT-EARLY, N=945], while MTX-IR pts were randomized to UPA 15mg QD or adalimumab (ADA) 40 mg eow or placebo (PBO), with continuous background MTX [SELECT-COMPARE, N=1629]. Both RCTs specifically enrolled pts at high risk for progression of joint damage (high disease activity including elevated hsCRP, presence of baseline erosions and ACPA and/or RF positivity2,3). The mean changes (Δ) from baseline (BL) in modified Total Sharp Score (mTSS), joint space narrowing (JSN), and erosion scores (ES) as well as the proportion of pts with no radiographic progression (ΔmTSS ≤0) at Weeks 24/26 and 48 were determined in both RCTs. Data were analyzed by linear extrapolation (LE) for missing data imputation and treatment switching, and as observed (AO).
Results: BL demographics have been reported previously2,3. At Weeks 24/26, UPA as monotherapy and in combination with background MTX significantly inhibited radiographic progression measured by mean ΔmTSS and the proportion of pts with no radiographic progression vs MTX and PBO, respectively (LE and AO). The significant inhibition of radiographic progression with UPA was maintained through Week 48 vs MTX (LE and AO) in EARLY and vs PBO (LE) in COMPARE. Following the switch of all PBO pts to UPA in COMPARE by Week 26, no further change in mean mTSS was observed through Week 48 (AO). The inhibition of radiographic progression vs comparators was not only observed for the overall mTSS scores but also its components – the JSN and ES in both RCTs (LE and AO).
Conclusions: UPA both as monotherapy, and in combination with background MTX, was effective in inhibiting the progression of structural joint damage through Week 48 in MTX-naïve, and MTX-IR patients, respectively.
SAFETY PROFILE OF UPADACITINIB IN RHEUMATOID ARTHRITIS: INTEGRATED ANALYSIS FROM THE SELECT PHASE 3 CLINICAL PROGRAM
Stanley B. Cohen1, Ronald van Vollenhoven2, Kevin Winthrop3, Cristiano A. F. Zerbini4, Yoshiya Tanaka5, Louis Bessette6, Ying Zhang7, Nasser Khan7, Barbara Hendrickson7, Jeffrey V. Enejosa7, and Gerd Burmester8. 1Metroplex Clinical Research Center, Dallas, USA, 2Amsterdam Rheumatology and Immunology Center ARC, Amsterdam, Netherlands, 3Oregon Health and Science University, Portland, USA, 4Centro Paulista de Investigaçao Clínica, Sao Paulo, Brazil, 5Univ of Occupational and Environmental Health, Kitayushu, Japan, 6Laval University, Quebec, Canada, 7AbbVie Inc., North Chicago, USA, 8Charité University Medicine, Berlin, Germany.
Objective: Assess overall safety of Upadacitinib (UPA) as monotherapy(mono) and combination therapy with background csDMARDs in pts with moderately to severely active RA.
Methods: Treatment-emergent adverse events (TEAEs) from 5 pivotal, randomized, double-blind, placebo-or active-controlled Phase 3 trials of UPA 15mg (included in all 5 trials) or 30mg QD (included in 4 trials) in RA pts were analyzed and summarized for integrated placebo (PBO) (3 trials; 12/14 weeks), integrated methotrexate (MTX) (2 trials; mean exposure: 36 weeks), originator adalimumab (ADA) (mean exposure: 42 weeks), UPA 15mg (mean exposure: 53 weeks) and UPA 30mg (mean exposure: 59 weeks) groups as exposure adjusted event rates (EAERs; events/100 patient-years [E/100PY]).
Results: Across the trials, 3834 pts received ≥1 dose of UPA 15mg (n=2630) or 30mg QD (n=1204), with no option to switch doses, for a total of 4020.1 PY of UPA exposure. EAERs of overall SAEs and AEs leading to discontinuation on UPA 15mg were comparable to ADA; while rates of both were higher on UPA 30 vs UPA 15mg and MTX. Across the studies, upper respiratory tract infection, nasopharyngitis and urinary tract infections were the most commonly reported AEs and occurred more frequently in the UPA compared with PBO. Rates of deaths were comparable across the treatment groups. Serious infection (SIEs) rates were comparable between UPA 15mg and ADA while higher on UPA compared with MTX. Rates of herpes zoster (HZ) were higher in both UPA groups vs MTX and ADA. The rates of SIE and HZ were higher on UPA 30 vs 15mg. Rates of malignancies (excluding non-melanoma skin cancer [NMSC]) and adjudicated MACE and VTE were comparable across the treatment groups. The rate of NMSC in UPA 15mg, MTX and ADA groups were similar with higher rates in the UPA 30mg group, however the rates for both UPA groups were in the range reported for RA patients treated with DMARDs3. The age-gender adjusted standardized incidence ratio (SIR, 95% CI) for malignancies other than NMSC (15mg: 0.98 [0.61, 1.49], 30mg: 1.49 [0.85, 2.42]) was within the range expected for the general population (SEER 18 Registry 2000-2015).
Conclusions: Rate of SIE on UPA 15mg was similar to ADA. The rate of HZ was higher on both UPA doses compared to MTX and ADA. The rates of VTE, MACE, and malignancy were comparable with that observed in the MTX and ADA groups while also being consistent with reported rates in the RA population.
A COMPARATIVE ANALYSIS OF UPADACITINIB MONOTHERAPY AND UPADACITINIB COMBINATION THERAPY FOR THE TREATMENT OF RHEUMATOID ARTHRITIS FROM TWO PHASE 3 TRIALS
Maya H. Buch1, Alvin F. Wells2, Andrea Rubbert-Roth3, Manish Jain4, Casey Schlacher5, Heidi S. Camp5, Yihan Li5, Yanna Song5, and Peter Nash6. 1University of Leeds & NIHR Biomedical Research Centre, Leeds, UK, 2Rheumatology and Immunotherapy Center, Franklin, USA, 3Kantonsspital St Gallen, St Gallen, Switzerland, 4Rheumatology, Great Lakes Clinical Trials, Chicago, USA, 5AbbVie Inc., North Chicago, USA, 6University of Queensland, Brisbane, Australia.
Objectives: To compare the efficacy of UPA monotherapy and UPA in combination with MTX using data from two Phase 3 trials of RA patients with an inadequate response (IR) to prior MTX therapy.
Methods: In SELECT-MONOTHERAPY, 648 MTX-IR patients were randomized to receive UPA 15 mg or 30 mg monotherapy once daily (QD), or continue with MTX monotherapy (cMTX; given as a blinded study drug), for 14 weeks. In SELECT-NEXT, 661 csDMARD-IR patients were randomized to receive UPA 15 mg or 30 mg QD or placebo (PBO) for 12 weeks on a background of csDMARDs. Only patients receiving concomitant MTX (with or without additional csDMARDs) at baseline in SELECT-NEXT were included in this analysis. The primary endpoints of both studies were the proportion of patients achieving ACR20 and DAS28(CRP) ≤3.2. Additional endpoints included ACR50/70, DAS28(CRP) <2.6, CDAI remission (≤2.8), CDAI low disease activity (LDA; ≤10), and change from baseline in HAQ-DI. Logistic regression or ordinary least squares analyses were used to compare outcomes with monotherapy versus combination therapy, adjusting for demographics and baseline disease characteristics.
Results: A total of 1114 patients were included in the analysis, of whom 648 received monotherapy in SELECT-MONOTHERAPY and 466 received combination therapy in SELECT-NEXT. Of the patients receiving combination therapy, 338 (72.5%) were receiving MTX background therapy only and 128 (27.5%) were receiving MTX plus other csDMARDs. Baseline characteristics were generally similar between the study cohorts; the majority of patients in both studies were female and of white ethnicity, with a mean age of approximately 55 years and a mean MTX dose of approximately 17 mg/week. Consistent with previously reported results from SELECT-MONOTHERAPY and SELECT-NEXT, both UPA monotherapy and UPA combination therapy led to significant improvements in efficacy outcomes versus cMTX/PBO+MTX. No significant differences were observed between UPA monotherapy and UPA combination therapy across a range of clinical endpoints, including ACR20/50/70 responses and measures of LDA and remission. In addition, improvements in quality of life as measured by HAQ-DI were similar with UPA monotherapy and combination therapy. Efficacy was comparable between the two UPA doses in the combination therapy group, whereas in the monotherapy group numerically higher responses were observed with UPA 30 mg versus UPA 15 mg.
Conclusions: In MTX-IR patients with RA, the efficacy of UPA appears comparable when administered as monotherapy or when given in combination with MTX.
UPADACITINIB TREATMENT AND THE ROUTINE ASSESSMENT OF PATIENT INDEX DATA 3 (RAPID3) AMONG PATIENTS WITH RHEUMATOID ARTHRITIS
Martin J. Bergman1, Yoshiya Tanaka2, Gustavo Citera3, Sami Bahlas4, Mira Ali5, Sebastian Meerwein6, Yanna Song5, and Vibeke Strand7. 1Drexel University College of Medicine, Philadelphia, USA, 2University of Occupational and Environmental Health, Japan, Kitakyushu, Japan, 3Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 4Medicine, King Abdulaziz University, Jeddah, Saudi Arabia, 5AbbVie Inc., North Chicago, USA, 6AbbVie GmbH Co. KG, Ludwigshafen, Germany, 7Division of Immunology/Rheumatology, Stanford University, Palo Alto, USA.
Objective: We assessed the effect of UPA treatment on RAPID3 in the SELECT-BEYOND, SELECT-COMPARE, and SELECT-MONOTHERAPY trials.
Methods: In SELECT-BEYOND1, bDMARD-IR patients received UPA 15 mg or 30 mg once daily (QD), or PBO for 12 wks while continuing stable csDMARD therapy. In SELECT-COMPARE2, MTX-IR patients received UPA 15 mg QD, PBO, or ADA 40 mg every 2 wks for 12 wks while continuing MTX. In SELECT-MONOTHERAPY3, patients received UPA monotherapy 15 mg or 30 mg QD, or continued MTX monotherapy (cMTX) for 14 wks. We assessed the least squares mean changes from baseline (BL) in RAPID3 and the proportion of patients reporting RAPID3 remission (≤3), low (LDA, >3 to ≤6), moderate (MDA, >6 to ≤12), and high disease activity (HDA, >12). Correlations between RAPID3 remission and remissions defined by CDAI, SDAI, and DAS28(CRP) were also assessed using Pearson correlation coefficients. Non-responder imputation was used for categorical endpoints, and last observation carried forward for continuous endpoints in patients who received rescue therapy in SELECT-COMPARE. Other continuous data are as observed. Data were analyzed descriptively.
Results: 498, 648, and 1629 patients were randomized in SELECT-BEYOND, -MONOTHERAPY, and -COMPARE, respectively. Numerically higher improvements from BL in RAPID3 were reported with UPA 15 mg and 30 mg treatment vs PBO in SELECT-BEYOND, and vs cMTX in SELECT-MONOTHERAPY. UPA 15 mg QD was also associated with greater reductions from baseline in RAPID3 vs PBO and ADA in SELECT-COMPARE. Of note, the improvements in RAPID3 with UPA and ADA exceeded the minimal clinically important difference (MCID = 3.84). The proportions of patients achieving RAPID3 remission were numerically higher in the UPA 15 mg and 30 mg groups vs PBO and cMTX in SELECT-BEYOND and SELECT-MONOTHERAPY, respectively. In addition, the proportions of patients in RAPID3 HDA were lower with UPA vs PBO and cMTX in these trials. In SELECT-COMPARE, higher rates of RAPID3 remission, with fewer patients in HDA, were evident with UPA 15 mg treatment vs PBO and ADA. Correlations between RAPID3 and other remission endpoints were significant (p<0.001; r=0.35–0.75) in all three trials at both baseline and Wk 12/14.
Conclusions: UPA was associated with improvements in RAPID3, both as monotherapy and in combination, in MTX-IR (SELECT-COMPARE and SELECT-MONOTHERAPY) or bDMARD-IR (SELECT-BEYOND) patients. UPA treatment can result in improved patient-reported disease activity, pain, and physical function in RA.
MACE AND VTE ACROSS MULTIPLE UPADACITINIB STUDIES IN RHEUMATOID ARTHRITIS: INTEGRATED ANALYSIS FROM THE SELECT PHASE 3 CLINICAL PROGRAM
Ernest Choy1, Iain B. McInnes2, John Cush3, Jacob Aelion4, Ying Zhang5, Nasser Khan5, Jianzhong Liu5, Heidi S. Camp5, Sebastian Meerwein6, William Rigby7, and Alexander T. Cohen8. 1CREATE Centre, Cardiff University, Cardiff, UK, 2University of Glasgow, Glasgow, UK, 3Baylor Scott & White Research Institute, Dallas, USA, 4Arthritis Clinic PLLC, Jackson, USA, 5AbbVie Inc., North Chicago, USA, 6AbbVie Deutschland GmbH & Co KG, Ludwigshafen, Germany, 7Dartmouth-Hitchcock Medical Center, Lebanon, USA, 8Guy’s and St Thomas’ NHS FT Hospitals, King’s College, London, UK.
Objective: Patients with RA have an approximate 2-fold increased risk of cardiovascular (CV) morbidity and mortality and venous thromboembolic events (VTE)1,2. Among RA patients, rates of major adverse CV events (MACE) and VTE were 0.3–0.7 incidences per 100 patient-years (PY)3 and 0.3–0.8 events per 100 PY4, respectively. Here we assess rates of MACE and VTE from the integrated safety database of the Phase 3 clinical program of Upadacitinib (UPA), an oral, potent, reversible, JAK1-selective inhibitor, in patients with moderately to severely active RA.
Methods: Treatment-emergent adverse events of MACE and VTE from 5 pivotal, randomized, blinded, Phase 3 trials of UPA 15 mg QD (all 5 trials) or 30 mg QD (4 trials) in RA patients were summarized into the integrated placebo (PBO), MTX, ADA 40 mg, UPA 15 mg and UPA 30 mg treatment groups. Data are presented as exposure adjusted event rates (EAERs, E/100 PY). All suspected MACE and VTEs were adjudicated by an external, independent, CV adjudication committee.
Results: Across trials, 3834 patients received ≥1 dose of UPA 15 mg (n=2630) or 30 mg (n=1204) with no option to switch doses (exposure =4020.1 PY), 1042 patients received PBO (256.8 PY), 530 patients received MTX (368.7 PY) and 579 patients received ADA 40 mg (467.8 PY). History of prior CV events (2-3%) and VTEs (4-7%) were comparable across groups.
The EAERs of MACE and VTE in the UPA groups were comparable to PBO, MTX and ADA. Approximately 40% of MACE events and 1 pulmonary embolism event (UPA 15 mg) were fatal. All patients with a MACE or VTE event had ≥1 CV risk factor (hypertension, diabetes, dyslipidemia) or ≥1 VTE risk factor (prior history of thrombotic event, obesity, or hypertension) at baseline, respectively.
Though treatment with UPA increased the levels of low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), their ratio remained constant over time. Analysis of data showed no association of LDL-C increases and MACE occurrences. In both UPA groups, neither a dose-response nor a pattern of time-to-VTE-onset (23 to 1127 days of UPA) was observed. Slight decreases in mean platelet count from baseline were observed.
Conclusions: EAERs of adjudicated MACE and VTE with UPA were comparable with MTX and ADA and consistent with reported background rates in the RA population. Similar to other JAK inhibitors, UPA increased the levels of lipids. However, no association between lipid levels and MACE could be established.
A COMPARISON OF UPADACITINIB PLUS METHOTREXATE AND UPADACITINIB PLUS OTHER CSDMARDS IN PATIENTS WITH RHEUMATOID ARTHRITIS: AN ANALYSIS OF TWO PHASE 3 STUDIES
Joel M. Kremer1, Filip Van den Bosch2, Andrea Rubbert-Roth3, Sebastião C. Radominski4, Gerd R. Burmester5, Heidi S. Camp6, Sebastian Meerwein7, Mark Howard6, Yanna Song6, Sheng Zhong6, and Bernard Combe8. 1Albany Medical College, Albany, USA, 2Ghent University Hospital and Ghent University, Ghent, Belgium, 3Kantonsspital St Gallen, St Gallen, Switzerland, 4Universidade Federal do Paraná, Curitiba, Brazil;, 5Charité-Universitätsmedizin, Berlin, Germany, 6AbbVie Inc., North Chicago, USA, 7AbbVie Deutschland, Ludwigshafen, Germany, 8CHU Montpellier, Université de Montpellier, Montpellier, France.
Background: Upadacitinib (UPA), a selective JAK1 inhibitor, has shown efficacy in patients with rheumatoid arthritis (RA) when combined with methotrexate (MTX) or other conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).1,2 However, the efficacy of UPA plus MTX has not been directly compared with UPA plus other csDMARDs.
Objectives: To compare the efficacy of UPA in combination with MTX versus UPA in combination with other csDMARDs in patients with an inadequate response (IR) to csDMARDs (SELECT-NEXT1) or biologic DMARDs (bDMARDs; SELECT-BEYOND2).
Methods: 661 patients in SELECT-NEXT and 498 patients in SELECT-BEYOND received UPA 15 mg or 30 mg once daily (QD) or placebo (PBO) for 12 weeks; all patients received concomitant csDMARD(s). The primary endpoints for both studies were rates of ACR20 response and DAS28(CRP) ≤3.2. Additional endpoints included DAS28(CRP) <2.6, CDAI low disease activity (≤10), and CDAI remission (≤2.8). Patients were grouped according to concomitant csDMARD use (MTX vs non-MTX csDMARDs); patients receiving both MTX and a non-MTX csDMARD were included in the MTX group. p-values were calculated based on a logistic regression model with treatment group and type of background csDMARD as fixed factors, adjusting for demographic and baseline factors. p-values from the interaction between treatment group and background csDMARD were also calculated, to assess the consistency of the effects of study treatments for different background csDMARD type. Non-responder imputation was used for missing data.
Results: In SELECT-NEXT and SELECT-BEYOND, 535 and 410 patients, respectively (~80%), were receiving concomitant MTX (mean dose 17 mg/week), and 124 and 82 patients were receiving non-MTX csDMARDs. Demographics and disease characteristics were broadly similar between treatment groups; the majority of patients were female and of white ethnicity, and around half were using oral corticosteroids at baseline. Across all subgroups, the proportion of patients achieving efficacy outcomes was higher with both UPA doses compared with PBO. There were no significant differences between efficacy outcomes with UPA in combination with MTX versus UPA in combination with non-MTX csDMARDs in either patient population. This included ACR20 response as well as low disease activity and remission defined by DAS28(CRP) and CDAI.
Conclusions: In this post hoc analysis, the efficacy of UPA in patients with RA appeared comparable whether administered in combination with MTX or non-MTX csDMARDs.
MONOTHERAPY WITH UPADACITINIB IN MTX-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 48 WEEKS
R van Vollenhoven1, T Takeuchi2, AL Pangan3, A Friedman3, S Chen3, M Rischmueller4, R Blanco5, RM Xavier6, and V Strand7. 1Amsterdam Univ Medical Centers, Amsterdam, Netherlands, 2Keio Univ School of Medicine, Tokyo, Japan, 3AbbVie Inc., N Chicago, USA, 4The Queen Elizabeth Hospital and Univ of Adelaide, Adelaide, Australia, 5Hospital Univ Marqués de Valdecilla, Cantabria, Spain, 6Univ Federal do Rio Grande do Sul Porto Alegre, Rio Grande do Sul, Brazil, 7Stanford Univ, Palo Alto, USA.
Objective: Assess safety/efficacy of upadacitinib (UPA) through 48wks in ongoing extension of ph3 SELECT-EARLY RCT.
Methods: Patients received UPA15 or 30mg monotherapy or MTX. Rescue therapy was offered if patients met the following: Wk12-24, <20% improvement from BL(Δ) in both TJC and SJC at 2 consecutive visits continued blinded study drug with optimized background RA medications; Wk26, patients with CDAI≤2.8 continued original study drug; patients with CDAI>2.8 and <20%Δ in TJC and SJC, on MTX, UPA15/30mg was added; patients on UPA15/30mg, MTX was added. Patients with CDAI>2.8 but ≥20%Δ in TJC and SJC, background medications were optimized. Efficacy data up to Wk48 are reported based on initial randomized treatment. For binary non-radiographic endpoints, NRI was used for missing data and rescue handling; for continuous non-radiographic endpoints, LOCF was used for rescue handling. Adverse events (AE) per 100 patient years (PY) are summarized up to a cut-off date of Aug 16 2018.
Results: Of 945 patients, 747 (79%) completed Wk48 treatment, 163 (17.2%) discontinued study drug prior to Wk48, 35 (4%) did not complete study. Primary reasons for discontinuation were AEs for 62 (6.5%) and lack of efficacy in 20 (2.1%) patients. At Wk26, UPA15/30 was added for 37 (12%) of patients on MTX; MTX was added for 19 (6%) and 9 (3%) of patients on UPA15 and UPA30, respectively. Cumulative exposures to MTX monotherapy, UPA15and UPA30 monotherapy were 314.4, 343.1 and 336.7 PYs, respectively. Through Wk48, patients on UPA15/30 vs MTX continued to have significantly greater improvements in clinical, functional and patient-reported outcomes. At Wk48, CDAI Remission (REM) was achieved by 33% and 40% of patients on UPA15 and 30 respectively vs 17% on MTX; 28% and 33% vs 13% achieved Boolean REM. At Wk48, ΔmTSS were significantly less on UPA15/30 vs MTX. Safety profile of UPA15/30 monotherapy was generally similar to MTX, except for total AEs and herpes zoster, which were higher with UPA15/30 vs MTX. There were 11 deaths (including 3 non-treatment emergent deaths).
Conclusion: UPA15 and 30mg monotherapy continued to show significant improvements in RA signs, symptoms and inhibition of structural damage vs MTX through 48wks. Only a small proportion of patients required MTX addition to UPA monotherapy at Wk26 to achieve and maintain response. Safety profile based on all exposure remained consistent with ph2 and 3 RCTs in RA, although integrated safety analysis of UPA across the full ph3 RA program will provide more comprehensive understanding of the benefit: risk profile of UPA in RA.
CLINICAL CHARACTERIZATION OF PATIENTS WITH SPONDYLARTHRITIS IN A DOMINICAN COHORT TREATED IN THE DIVISION OF RHEUMATOLOGY OF THE REGIONAL UNIVERSITY HOSPITAL JOSÉ MARÍA CABRAL Y BÁEZ
Carmen Maria Tineo Rodriguez1, Glenny Paulino, Catherine Rodriguez, Greisy Diaz, Romilda Salas, Franchezca Alvarez, Yanela Surlel, Diana Rozon, Anllely Tapia, Yamell Camilo, Piery Guzman, Idelfy Sanchez, and Esthela Loyo. 1Hospital Regional Universitario Jose Maria Cabral Y Baez, Santiago, Dominican Republic.
Introduction: The spondylarthritis are chronic rheumatic disorders that encompass a series of diseases that share similar genetic, clinical, radiological and outcome characteristics. However, disparities in the characteristics of the disease have been reported in ethnic groups and little is known about the clinical behavior of spondyloarthritis in the Dominican population.
Objective: To identify the clinical, radiological, serological and pharmacological characteristics of patients diagnosed with spondyloarthritis in a Dominican Republic cohort treated in the Division of Rheumatology of the Regional University Hospital José María Cabral y Báez.
Materials and Methods: This is a descriptive, crossd-sectional and primary source analysis of the records stored between 2008 and 2018. We included 104 patients diagnosed with spondyloarthritis of both genders. The variables evaluated were sociodemographic data, clinical characteristics, acute phase reactants, HLA-B27 and treatment. The data were presented in frequencies and percentages in tables and graphs. The statistical analysis was performed through the Chi square test.
Results: The cases corresponded to 56 men and 48 women with an average age of 43 ± 15 years with an average disease duration of 8 years. 18.3% (n = 19) of the patients had a family history of spondyloarthritis. There were comorbidities such as hypertension (28.8%) and diabetes mellitus (6.7%). HLA-B27 positivity occurred in 45.7%. 91.3% were under treatment with NSAIDs and 70.2% with biologicals. Ankylosing spondylitis occurred in 57.7% of the cases and psoriatic arthritis in 28.8%. The most common type of joint involvement was mixed, axial and peripheral.
Conclusions: Ankylosing spondylitis and psoriatic arthritis were the most frequent clinical forms. Ankylosing spondylitis was more prevalent in men and associated with psoriasis in women. The clinical manifestations that were statistically significant were inflammatory back pain, pain in alternating buttocks and dactylitis.
Key words: Spondylarthritis, Psoriatic arthritis, Ankylosing spondylitis, HLA-B27.
INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH TOFACITINIB
Marisel Vanesa Bejarano1, Maria Natalia Tamborenea1, Mario Goñi2, Lina Saldarriaga3, Cecilia Pisoni4, Rodrigo García Salinas5, Mariana Salcedo6, Claudia Helling7, and Adrian Salas7. 1Hospital Rivadavia, Argentina, 2ILAR, Argentina, 3Hospital Universitario San Jorge, Colombia, 4CEMIC, CABA, Argentina, 5Hospital Italiano de la Plata, La Plata, Argentina, 6IICZAR, Argentina, 7Pfizer SRL, Argentina.
Objectives: To describe the course of dyspnea, spirometric parameters, DLCO and high-resolution computed tomography (HRCT) findings in RA patients with associated ILD, who received Tofacitinib for a period of 12 months.
Materials and methods: Patients with a diagnosis of RA who fulfilled ACR 1987/ACR-EULAR 2010 criteria, with associated ILD, were included. Tofacitinib dose used was 10 mg / day. Design: Descriptive, medical records review, multicenter study. The following variables were examined: change at 12 months from baseline in the degree of dyspnea (according to the modified scale of dyspnea MMRC), forced vital capacity (FVC), DLCO and findings in HRCT.
Results: Fifteen patients were included. 60% (n: 9) were women. The mean age was 64.4 years (± 10.92). The median time of RA duration was 9 years (IQR: 4-40). All patients were double seropositive (RF and ACPA). The median time of ILD duration was 4 years (IQR: 1-24). 60% (n: 9) of patients had previously received methotrexate.33% of patients (n: 5) had received previous treatment with biological agents. The average time of treatment with tofacitinib was 1.93 years (± 0.96).
47% of patients (n = 7) received tofacitinib monotherapy. 27% (n: 4) of the patients had grade 3-4 dyspnea at baseline. Improvement in the dyspnea scale was observed in 8 patients.
At 12 months, 4 patients achieved a FVC> 80%. The average DLCO at baseline was 45.6 (± 18.84), with improvement of 30% at 12 months in 4 patients. No progression of the disease was observed in HRCT at 12 months in any of evaluated patients.
Conclusion: The present preliminary study was performed with patients of daily practice, not being available in all cases, the corresponding respiratory functional examinations. However, despite these limitations, none of the patients showed worsening of dyspnea, and improvement was observed in some patients. Respiratory functional examinations and DLCO, remained stable after treatment in the majority of patients, but 4 patients presented improvement from baseline parameters. Results of recent post hoc analysis suggest that development of interstitial lung events is numerically lower in patients who received Tofacitinib compared to placebo group (IR: 0.18). It should be noted that these results were obtained in patients included in clinical trials, which differ widely from daily practice patients, being longitudinal studies necessary, of larger sample size, with systematized controls of pulmonary function and images, to corroborate this hypothesis.
VALIDATION OF THE QUALITY OF LIFE-RHEUMATOID ARTHRITIS SCALE II (QOL-RA II) IN ARGENTINEAN PATIENTS WITH PSORIATIC ARTHRITIS
Tatiana Barbich1, Carolina Ayelen Isnardi1, Emilce Edith Schneeberger1, Virginia Carrizo Abarza1, Gisele Luna1, and Gustavo Citera1. 1Irep, Buenos Aires, Argentina.
Objectives: To validate the QOL-RA II questionnaire in a Psoriatic arthritis (PsA) cohort and to determine the impact of different sociodemographic and clinical factors on the quality of life in these patients.
Material and methods: A cross-sectional study was carried out. Patients ≥18 years old, with PsA according to CASPAR criteria from the RAPSODIA cohort were included. Sociodemographic data, disease characteristics and presence of extra-articular manifestations and comorbidities were recorded. Joint count (66/68), presence of dactylitis and enthesitis (MASES), nail and skin involvement, morning stiffness, ESR and CRP were registered. DAPSA, MDA and VLDA were calculated. Self-questionnaires were administered: HAQ-A, EQ-5D-3L, PsAQoL, DLQI, QOL-RAII, GAD-7 and PHQ-9.
Statistical analysis: Student's T-test, Chi2 test, ANOVA. Spearman's correlation. Reliability by Cronbach's α. Linear regression models.
Results: 52 patients were included, 65.4% were female, with a median (m) age of 56 years (IQR 43.2-65.7) and median disease duration of 12 years (IQR 5-17). DAPSA m was 12.8 (IQR 6.8-21.4) and 14 (27%) were on MDA. QOL-RA II m was 6.5 (IQR 5.1-7.9). The QOL-RA II showed very good reliability (0.95), floor and ceiling effect were 0% and 3.8%, respectively. There were no missing questions. Redundancy between question N° 8 and N° 4, N° 5 and N° 7 was observed. QOL-RA II correlation with other quality of life questionnaires was reasonable (DLQI: Rho -0.48, PsAQoL: Rho -0.40, EQ-5D-3L: Rho 0.47). The quality of life was significantly worse in patients presenting dactylitis (• 4.4±1.6 vs • 6.5±1.9, p=0.03), anxiety (GAD-7 ≥ 5) (• 5.9±1.6 vs • 7.1±2.2, p=0.04) and major depression (PHQ-9 ≥10) (• 5.5±1.5 vs • 6.7±2.1, p=0.04). In other way, patients who were in remission by DAPSA had a better quality of life (• 7.5±2.3 vs • 4.3±2.1, p=0.01), as well as those on VLDA (• 8.1±2.1 vs • 6.1±1.8, p=0.01). In the multivariate analysis, adjusting for age, sex, and disease duration, disease activity assessed by DAPSA was associated with poorer quality of life [Coefficient β: -0.45, 95% IC: -0.14 -0.02), p=0.008].
Conclusion: The QOL-RA II questionnaire showed good reliability in patients with Ps; however, the presence of redundancy was detected among some questions and it showed poor correlation with other quality of life questionnaires.
JUVENILE SYSTEMIC SCLEROSIS IN TWO PEDIATRIC RHEUMATOLOGY CENTERS. 20 YEARS´ EXPERIENCE
Marina Carrillo1, Gabriela Necul1, Alejandra Pringe1, Brusco Isabel1, Vanesa Cervetto1, Maria Marcantoni1, Tatiana Velasco2, Viviana Mastri2, Mariana Fabi2, and Jimena Gomez Sosa1. 1Hospital Pedro De Elizalde, Buenos Aires, Argentina, 2Sor María Ludovica de La Plata, La Plata, Argentina.
Introduction: Juvenile Systemic Sclerosis (JSS) is an autoimmune disease with multisystemic impact. Its etiology is unknown and its presentation in pediatric patients is infrequent (<2% in children under 10 years, 1,2-9% in >10). Its course is prolonged, frequently characterized by systemic and progressive symptoms, which can lead to incapacity and death.
Due to its low prevalence it´s important to be aware of the initial symptoms and course so as to arrive to an early diagnosis and give opportune treatment to prevent multiorgan involvement.
Objective: To describe the initial presentation, course, organ involvement and treatment in pediatric patients with JSS in two pediatric rheumatology centers over the last 20 years.
Materials and methods: Observational, descriptive, medical records review, cross-sectional study
Population: Patients under 18 years of age, with JSS diagnosed by PRES/ACR/ERULAR 2007 criteria, treated in either Center between June 1999 and June 2019.
Demographic data and organ involvement were registered according to classification criteria (PRES/ACR/ERULAR 2007) at first visit, 6 months and then annually until 5 years of follow-up or last visit. For continuous variables each mean with its SD (or median and IQR) were calculated. Categoric variables are presented as absolute numbers.
Gastrointestinal and pulmonary involvement association was calculated by Chi square distribution curve. Kaplan Meier curve was used to describe when the diagnosis of organ involvement occurred. Statistical analysis by SPSS 20.0
Results: 23 patients with JSS were included. 17 were female. Median age at initial symptoms was 8,68 years (0,33-15); median age at diagnosis 10,04 years (1,4-15,33)
Interval between fist symptoms and diagnosis 16± 19 months; time of follow-up 52,9±47,7 months
At diagnosis 15/23 patients were ANA + and 1/17 was Scl70+
Initial symptoms: diffuse cutaneous involvement 17; musculoskeletal 8; arthritis 8; arthralgia 8; Raynaud phenomenon 15; pitting scars and digital ulcers 11.
Pulmonary involvement in 14 patients: pathologic CT chest scan 11 (4 at initial assessment); low DLCO in 11 (3 at beginning/first visit)
Median for survival regarding pulmonary involvement was 29,4 months±11,73 months (IC 95 % 6,40-52,398).
Pulmonary hypertension: 4 patients (2 at firs visit). Gastrointestinal involvement: 7
Other organs were less frequently affected, including 1 patient with CNS involvement.
3 deaths were registered: due to renal crisis, pulmonary interstitial involvement and cardiogenic shock secondary to restrictive myocardiopathy.
Conclusions: Cutaneous involvement was the main clinical manifestation. The lung was the most frequently affected organ. Renal crisis and restrictive myocardiopathy are infrequent manifestations at initial disease and as cause of death in children.
DOES POLYPHARMACY IN RHEUMATOID ARTHRITIS PATIENTS AFFECT THE TREAT-TO-TARGET STRATEGY?
John Fredy Jaramillo Gallego1, Javier Rosa1, Marina Scolnik1, Mayra Alejandra Tobar Jaramillo1, Maria Victoria Garcia1, Leandro Ferreyra1, and ER Soriano1. 1Hospital Italiano De Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
Background/purpose: Polypharmacy (PP) is an important risk factor for drug toxicity, delirium, falls, hospitalizations and death. Patients with rheumatoid arthritis (RA) often have comorbid conditions and receive PP. Treat to target strategy (T2T) implies a drug escalation and rheumatologists may not apply it in patients with PP. Our objective was to analyze if PP affects T2T in a real-world scenario.
Methods: Observational, medical records review cohort study. Patients with a new RA diagnosis (ACR/EULAR 2010 criteria) after 2010, over 18 years of age, belonging to a Health Management Organization (HMO) from a university tertiary hospital, with a minimum follow-up period of 2 years, were included. PP was defined as consumption greater than or equal to 5 medications at the time of RA diagnosis, regardless of the medication used for RA, administered for a minimum period of 6 months. T2T strategy was defined as accomplished if an escalation in treatment was done when the patient had moderate or high disease activity at medical visit (by DAS28 and/or CDAI), without a significant improvement with respect to the previous visit. Prevalence of PP at RA diagnosis was calculated and RA patients were divided in those with PP at RA diagnosis time and those without. The first 2 years of disease were analyzed and compared between both groups: clinical and demographic characteristics, percentage of visits where T2T was applied, treatments received during that period. A multivariate logistic regression analysis was performed in order to identify factors associated with no T2T compliance.
Results: 147 patients with RA were included, 86% women, with an average age at diagnosis of 60 years (SD: 15.8). The prevalence of PP at RA diagnosis was 12% (17 patients). Table 1 shows the comparison between patients with and without PP. Patients with PP showed a greater frequency of erosions at baseline and after 2 years of disease, a greater use of corticosteroids at 2 years, higher percentage of hospitalizations and a higher mortality. In the multivariate logistic regression analysis, no compliance of the T2T strategy was only associated with the consumption of corticosteroids at 2 years (OR: 0.36, CI95%: 0.15-0.85; p=0.019) and no association was found with PP at the beginning of the disease.
Conclusion: The prevalence of PP in our patients with a new RA diagnosis was 12% and was associated with more baseline erosions, a higher consumption of steroids, and a higher frequency of hospitalizations and mortality during the first 2 years of the disease. No relationship between PP and adherence to the T2T strategy was demonstrated. In the multivariate logistic regression analysis, no compliance with the T2T strategy was only associated to the consumption of corticosteroids at 2 years, may be reflecting a poorer disease control.
HOSPITALIZATIONS IN PATIENTS WITH SLE: IMPACT OF ANTIMALARIAL COMPLIANCE
Álvaro Lugo-Mata1, Yurilis Fuentes-Silva1, Carlota Acosta2, Luisa Ortega2, Soham Al Snih3, Martin A. Rodriguez4, and Irama Maldonado2. 1Universidad De Oriente, Ciudad Bolívar, Venezuela, 2Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Venezuela, 3Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, USA, 4Sealy Center of Aging, University of Texas Medical Branch, Galveston, Texas, USA.
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease with potential complications that often result in hospitalizations. This study describes local data on hospitalizations of SLE patients and socio-demographic variables that have impact on the disease outcome.
Methods: Medical records of SLE patients hospitalized during a 6-year period (01/01/2012–12/31/2017) were analyzed in a single center in Venezuela: socio-demographic data, variables related to the disease and to hospitalizations. Criteria set of Helsinki declaration was applied. Statistical analysis was done using the Chi-square test, Fisher's exact test and Student's t test. p-values of < 0.05 were considered statistically significant.
Results: A total of 132 SLE patients and 305 hospitalizations were identified, with average of 2.3 per patient. All patients fulfilled the 1997 ACR or the 2012 SLICC criteria. Female-to-male ratio was 8:1. Average age was 35.8±12.8 years. Disease duration was 7.8±5.7 years. Mean SLEDAI and SLICC Damage Index at admission time were 7.0±6.7 and 2.0±2.2, respectively. The most common reasons for hospitalization were SLE flare (59%) and infection (35.1%). The most common lupus medications were antimalarials (77.7%), glucocorticoids (60.3%), and immunosuppressants (34.8%). The median length of hospitalization was 13±11.7 days. There were 32 cases of hospitalizations in 25 patients with criteria for ICU admissions (10.5%). Fifteen patients died (11.36%) during hospital stay. Characteristics regarding ICU admissions are shown in table 1.
Conclusion: Admissions due to SLE flares and infection are frequent. Poor outcomes were related with higher rates of deaths and low antimalarial compliance. Venezuelan humanitarian crisis probably could explain these findings.
IMPACT OF TREATMENT COMPLIANCE IN THE QUALITY OF LIFE IN VENEZUELAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS. THE SIGNATURE OF A HEALTH CRISIS
Yurilis Fuentes-Silva, BSc1, Fhabián Carrión-Nessi, BSc1, Allen Antuarez-Magallanes1, Carlota Acosta2, Irama Maldonado2, Luisa Ortega2, Mayra Rauseo2, Soham Al Snih3, and Martin A. Rodriguez4. 1Universidad de Oriente, Ciudad Bolívar, Venezuela, 2Complejo Hospitalario Universitario Ruiz y Páez, Ciudad Bolívar, Venezuela, 3Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, USA, 4Sealy Center of Aging, University of Texas Medical Branch, USA.
Objective: Many aspects related to the healthcare system and socio-demographic factors can have a direct influence in the quality of life of patients with systemic lupus erythematosus (SLE). In the midst of a humanitarian crisis currently taking place in Venezuela, characterized by limited access to medical care and a marked shortage of medicines, we sought to examine the quality of life in SLE patients and identify socio-demographic variables associated to it.
Methods: All patients (N=100) fulfilled the 1997 ACR criteria or the SLICC 2012 classification criteria. Health-Related Quality of Life (HRQoL) was evaluated using the Lupus Quality of Life (LupusQoL) instrument comprising 34 items grouped into 8 domains; and assessed by a patient using a 4-point Likert scale. Each domain is assessed separately, the mean raw domain score is divided by four and then multiplied by 100. The obtained score determines the patient’s quality of life in a given domain (0 – worst HRQoL 100 – best HRQoL). A Spanish version of the questionnaire was validated. The study was conducted according to the criteria set by the declaration of Helsinki and each subject signed an informed consent before participating in the study. Statistical analysis was done using univariate and multivariate linear regression analysis and the Mann-Whitney U test. p-values of < 0.05 were considered statistically significant.
Results: Ninety-three percent of patients were female, mean age was 42.2±12.8 years, disease duration 10.5±8.9, and years of education 11.5±4.4. Mean SLEDAI and SLICC Damage Index were 3.1±4.7 and 0.6±1.1, respectively. The HRQoL domains most frequently affected were: burden to others, fatigue, pain and emotional health in decreasing order. Age was inversely correlated with all LupusQol domains. For those patients with a drug prescription compliance was 65.6% for antimalarials (n=90), 71.4% for corticosteroids (n=84) and 42.2% for immunosuppressants (n=45). HRQoL for physical health was the most affected domain in SLE patients who were not compliant with antimalarials (p=0.02). Also, the physical health, emotional health and fatigue domains were significantly affected when patients in combined therapy failed at least one of these three type of medications.
Conclusion: A considerable proportion of patients were non-compliant to prescribed drugs mainly due to a critical shortage of medicines occurring in the context of a current humanitarian crisis in Venezuela. This situation had a significant impact in the perception of dimensions in all of HRQoL.
RETROPERITONEAL FIBROSIS- A SINGLE CENTER EXPERIENCE
Serdal Ugurlu1, Mert Oztas1, and Emir Cerme1. 1Istanbul University-Cerrahpasa, Department of Medicine, Division of Rheumatology, Istanbul, Turkey.
Background: Idiopathic retroperitoneal fibrosis (iRPF) is a rare, chronic, progressive disorder of unknown etiology and characterized by the presence of inflammatory and fibrous retroperitoneal tissue.
Objective: We evaluated iRPF cases from a single institution cohort to describe the features of patients (pts) with iRPF.
Methods: Twenty-eight iRPF patients who were being followed in our outpatient clinic between 2009 and 2018 were included. The demographic characteristics, clinical and radiologic findings, medical and interventional therapies were collected from the available medical records and reported.
Results: We evaluated the data from 28 patients (17M). The mean age at the time of diagnosis was 53±10,57 years, median follow up was 46 (IQR:23-67) months. Fifteen patients presented with abdominal-pain which was the most common initial complaint. Twenty-one patients had hydronephrosis (11 bilateral hydronephrosis, 5 right and 5 left hydronephrosis) at disease onset. Laboratory tests showed an elevated ESR in 15 of 23 cases (65.2 %), with a median value of 39 mm/h (IQR:17-88); CRP was elevated in 19 of 28 patients (68%), with median value 11 (IQR:5,5-46,5). Mean serum creatinine level was 1,14 mg/dL IQR (0,83-1,9). Tissue involvement was detected with computed tomography in 25 (89%) patients. In addition, 18 F-FDG-PET was ordered in 19 patients and in 16 of them (84%) it was positive for tissue involvement of iRPF. Among these 16 pts, control 18 F-FDG-PET scan was obtained in 13 after at least 6 months of follow-up. Remission was observed in 7 pts in the control 18 F-FDG-PET scan. Twenty-seven pts were initially treated with glucocorticoids and the mean initial oral prednisone dose was 45,5±13,8 mg/day. Prednisone was discontinued in 4 patients after remission and for the remaining 23 pts 12 pts’ prednisone was tapered <5 mg/day at a mean of 9 (IQR:6,7-22,5) months. The remaining patient was treated with tamoxifen. Final median values of ESR and CRP were 10 mm/h (IQR:4,7-17,7) and 4,4 mg/l (1,9-7,7), respectively (p= 0.001 and p=0.002). Final median serum creatinine level was 1,03 (IQR:0,78-1,28) (p=0,2). Thirteen pts (%46) who did not respond to the initial prednisone therapy were treated successfully with Rituximab. Twenty-one pts had ureteral stents and 11 of them are stent free at the final visit. 2 pts had ureterolysis but the procedure failed in one patient. None of the pts died during the follow-up.
Conclusion: Prompt interventional approaches are valuable bridging therapies for pts who presented with hydronephrosis. Obtaining a biopsy sample could be hazardous or not possible because of the location of the lesions; so imaging modalities add great value to the diagnose of iRPF.
CLINICOPATHOLOGICAL CORRELATION OF AUTOIMMUNE DISEASES: AN AUTOPSY-BASED STUDY DURING A PERIOD OF 14 YEARS IN A THIRD-LEVEL COLOMBIAN HOSPITAL
Ariana Villarreal Gómez1, Silvia Natalia Suárez Mantilla2, Julio César Mantilla Hernández1,2, and Rubén Darío Mantilla Hernández3. 1Universidad Industrial De Santander, Bucaramanga, Colombia, 2Hospital Universitario de Santander, Bucaramanga, Colombia, 3Centro de Estudio de Enfermedades Autoinmunes, Bogotá, Colombia.
Objective: To describe the clinical, sociodemographic characteristics and pathological findings of deceased patients with Autoimmune Diseases.
Materials and methods: This is an observational, descriptive and medical records review cross-sectional study of autopsy cases carried out in the Department of Pathology of Hospital Universitario de Santander, an educational third-level hospital in north-east Colombia, between January 2004 and December 2019.
Results: Of 4526 autopsy protocols, 2341 (51.72%) were included, among these, 35 protocols (1.49%) belonging to the deceased with a diagnosis of Autoimmune Disease were evaluated: 11 (31.43%) men and 24 (68.57%) women, the majority belonging to the early adulthood age group. 10 Autoimmune Diseases were found, being Systemic Lupus Erythematosus (SLE) the most frequent (40%), followed by Rheumatoid Arthritis (28.57%) and Autoimmune Hepatitis (8.57%). The most prevalent general causes of death were as follows: Infection (48.57%), respiratory failure (14.29%), and cardiovascular failure (14.29%). Among the infectious cases, sepsis was the most frequent cause of death (70.59%), highlighting Mycobacterium tuberculosis as the etiological agent in 3 cases. 21 (60%) patients were on immunosuppressive medication.
Conclusions: This is the first worldwide autopsy-based study reported in literature. More studies focused on mortality in patients with Autoimmune Diseases are required to broaden the knowledge of the most frequent causes and risk factors for death, allowing the clinician to emphasize therapeutic actions on these causes, particularly infections, both in patients with and without immunosuppressive therapy.
CAUSES OF DEATH IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AUTOPSIED DURING A PERIOD OF 14 YEARS IN A THIRD-LEVEL COLOMBIAN HOSPITAL
Ariana Villarreal Gómez1, Silvia Natalia Suárez Mantilla2, Julio César Mantilla Hernández1,2, and Rubén Darío Mantilla Hernández3. 1Universidad Industrial De Santander, Bucaramanga, Colombia, 2Hospital Universitario de Santander, Bucaramanga, Colombia, 3Centro de Estudio de Enfermedades Autoinmunes, Bogotá, Colombia.
Objective: To describe the clinical, sociodemographic characteristics and pathological findings of deceased patients with Systemic Lupus Erythematosus.
Materials and methods: This is an observational, descriptive, medical records review, cross-sectional study of autopsy cases carried out in the Department of Pathology of the Hospital Universitario de Santander, an educational third-level hospital in north-east Colombia, between January 2004 and December 2019.
Results: Of 4209 autopsy protocols evaluated, 2341 (51.72%) were included once all perinatal autopsies were omitted. Among these, 14 (0.60%) were from patients with a diagnosis of Systemic Lupus Erythematosus (SLE) and were evaluated. 84% were women, with a male: female ratio of 0.16:1. Early adulthood was the most frequent age range, with an average of 35.25 years. The kidney was the most commonly SLE affected organ. The majority of deaths were attributed to infection (42.86%), followed by cardiovascular causes (21.43%). 3 cases corresponded to pregnant women, whose causes of death were sepsis (2 cases) and pulmonary thromboembolism (1 case). Furthermore, 9 subjects (64%) were on immunosuppressive therapy.
Conclusions: This is the first worldwide autopsy-based study of patients with SLE reported in literature. The majority of our cases corresponded to women, despite the association between male sex and increased mortality; however, our results were able to strengthen the previously established concept of lupus nephritis as a factor linked to death. In addition, we consider important to do an infection panel test to SLE patients, especially in those receiving immunosuppressive medication, considering that infection remains one of the main causes of death, as we have shown in this study.
INTERSTITIAL LUNG DISEASE IN LATE ONSET SYSTEMIC SCLEROSIS
Taskin Senturk1, and Gokhan Sargin1. 1Adnan Menderes University, Aydin, Turkey.
Introduction: Systemic sclerosis (SSc) is an autoimmune disease with onset between 40 and 50 years of age. It has been reported that late-onset SSc is a milder form of the disease with different organ involvement compared to younger patients. It is unclear whether there are differences in the clinical features of the disease as a function of age. This may be due to the inconsistency of previous data. The aim of this study was to determine the clinical features of late-onset SSc patients and SSc patients with interstitial lung disease (ILD) in the geriatric age group.
Methods: Patients aged 65 years or older who were diagnosed with SSc according to the 2013 ACR/EULAR SSc classification criteria were included in the study. Demographic characteristics, clinical findings, erythrocyte sedimentation rate (ESR), CRP, hematological and immunological parameters were recorded. ILD was defined as the presence of interstitial fibrosis or icy glass in the HRCT. Descriptive statistics were shown as n (%). Data were analyzed by using SPSS 21.0 and Chi-square, T-test and Mann Whitney U tests were used for the analysis.
Results: The mean age of the 26 patients included (21 female, 5 male) was 70.5±4.1 years. ANA was positive in 88.5% of the patients. 10 patients had diffuse and 16 patients had localized skin involvement. In 24 (92.3%) patients, the first symptom was Raynaud's phenomenon. Musculoskeletal symptoms were found in 18 patients, telangiectasia in 8, calcinosis in 1, ILD in 11, cardiac involvement in 8, and malignancy in 1 patient. The mean age of the patients with ILD was 70.3±4.5 years. 63.6% of these patients were positive for anti-scl-70. No statistically significant difference was found between both groups (with and without ILD) in terms of age, sex, ESR, CRP, hemoglobin, leukocyte, and platelet values. Diffuse skin involvement, cardiac involvement, and anti-scl-70 positivity were higher in the ILD group.
Conclusion: Localized skin involvement is more common in patients with late-onset SSc, however diffuse skin involvement is more common in late-onset SSc with ILD. In the geriatric group, cardiac involvement is often associated with ILD and patients have a high risk for organ involvement.
PREDICTORS OF MORTALITY AND FUNCTIONAL IMPACT OF IMMUNOSUPPRESSIVE TREATMENT IN AUTOIMMUNE INTERSTITIAL LUNG DISEASE: A MULTICENTER STUDY
Florencia Vivero1, Daniel Martin Iglesias2, Juan Manuel Vandale1, Marina Oliver1, Victoria Gandara1, Carolina Isnardi3, Mónica Sacnun4, Mariana Lagrutta5, Janet Balverdi6, Noelia Bersano4, Franco Pacello7, Natalia Cuccuchiaro8, Ramiro Gomez9, Maria Victoria Collado10, Alejandro Martinez11, Sofia Velez12, Diego Vila13, and Guillermo Ruiz Irastorza2. 1Hospital Privado de Comunidad, Mar del Plata, Argentina, 2Hospital Universitario Gurutzeta - Cruces, Barakaldo, España, 3Instituto de Rehabilitación Psicofísica, Buenos Aires, Argentina, 4Hospital Provincial, Rosario, Argentina, 5Hospital Centenario, Rosario, Argentina, 6Hospital Privado de Córdoba, Argentina, 7Hospital Escuela del Litoral de Paysandú, Paysandú, Uruguay, 8Hospital Señor del Milagro, Salta, Argentina, 9Hospital de Clínicas "José de San Martín", Buenos Aires, Argentina, 10Instituto de Investigaciones Médicas "Alfredo Lanari", Buenos Aires, Argentina, 11Fundación Respirar, Buenos Aires, Argentina, 12Hospital Británico, Buenos Aires, Argentina, 13Hospital San José de Capilla del Señor, Zárate, Argentina.
Objective: The main goal of this study was to examine the functional response to immunosuppressive treatment of interstitial lung disease associated to connective tissue disease (CTD-ILD). The secondary objective was to identify predictors of functional evolution.
Methods: Observational, multi-centric study involving 30 centers from Argentina, Uruguay and Spain. All participating centers provided multi-disciplinary specialized care. Response to treatment was evaluated according to the changes in forced vital capacity (FVC%) at 6-12 months. The following possible outcomes were defined: worsening: decline of FVC >10% with respect to the baseline; improvement: increase of FVC >10% with respect to the baseline; and stability: changes of FVC <10%. Mortality of all causes was recorded. Potential predictors of response were examined. Multivariable analysis was performed including variables of interest and significance (p<0.1). Improvement and combined worsening or death variables were defined as outcomes.
Results: This study comprised 160 patients; mean age 50.6 years (SD 13); 135 (84.4%) women. The most frequent CTD was systemic sclerosis (SSc) in 84 (52.5%) followed by idiopathic inflammatory myopathy (IIM) in 49 (30.6%) and Sjögren Syndrome in 20 (12.5%). Glucocorticoid (GC) use was predominant in IIM (98% vs 89% in SSc vs 76 % in others) as well as the use of GC pulses (49% in IIM vs 25% in SSc vs 22% in others) and prednisone median doses (19 mg/day in IIM vs 12 mg/day in others vs 5 mg/day in SSc). In SSc group cyclophosphamide was predominant (66% vs 14% mycophenolate vs 7% azathioprine). In IIM and others CTD, treatment strategies were heterogeneous.
The outcomes were: stability (79, 49.4%), improvement (46, 28.8%) and worsening (35, 22.0%). Functional worsening was more frequent in SSc (27% vs 18% in IIM vs 11% in others). Functional improvement was higher in IIM (45% vs 20% in SSc vs 26% in others).
In the multivariate analysis, worsening or death was associated with the time between symptoms of ILD to treatment (p=0.005), severe infections (p<0.001) and prednisone mean daily doses (p=0.048). Improvement was associated with subclinical disease (p= 0.007), diagnosis of IIM (p=0.027), low FVC at baseline (p<0.001) and GC pulses (p=0.02).
Conclusions: Early detection and therapeutic intervention in CTD-ILD could modify the course of these entities.
SSc-ILD presented worse prognosis as compared to other CTD-ILD, while IIM-ILD showed better response to immunosuppressive treatment.
The use of GC pulses followed by low prednisone daily is a reasonable alternative to standard of care.
No specific immunosuppressive drug was associated with better outcome.
IMPACT OF DEPRESSION AND ANXIETY IN PATIENTS WITH PSORIATIC ARTHRITIS
Virginia Carrizo Abarza1, Carolina Ayelen Isnardi1, Emilce Edith Schneeberger1, Barbcih Tatiana1, Gisele Luna1, JM Dapeña2, Magdalena Cavalleri1, and Gustavo Citera1. 1Irep, Buenos Aires, Argentina, 2Hospital General de Agudos Dr. Enrique Tornú, Buenos Aires, Argentina.
Objectives: To determine the prevalence of depression and anxiety in PsA patients and to establish their relationship with different sociodemographic and clinical factors.
Material and methods: Consecutive patients ≥18 years of age, with PsA according to the CASPAR criteria were included. Patients with difficulties in answering self-questionnaires (illiterate, blind) and/or with decompensated comorbidities were excluded. Sociodemographic data, comorbidities, psychiatric diseases, fibromyalgia, clinical characteristics of PsA and disease activity were recorded. Self-administered questionnaires: EQ-5D-3L, QOL-RA II, PsAQoL, DLQI, HAQ-A. Depression and anxiety were clasiffied as mild, moderate, moderate/severe and severe according to PHQ-9 and GAD-7values. Statistical analysis: Student's T-test, ANOVA and Chi2. Multiple linear regression.
Results: 65 patients were included, 61.5% were female, with a median (m) age of 57 years (IQR 45.5-65.5), and median disease duration of 12 years (IQR 5-17.5). DAPSA m 14.4 (IQR 7.6-22.4). 16 (24.6%) patients were in MDA. 14 (21.5%) had a diagnosis of some psychiatric disorder and 10 were under treatment. PHQ-9 m 6 (IQR 1-10.5) and GAD-7 m 5 (IQR 1-10). The prevalences of major depression (PHQ-9 ≥10) and anxiety disorder (GAD-7 ≥5) were26.2% and 56.9%, respectively. 19 (29.2%), 7 (10.8%), 9 (13.8%) and 1 (1.5%) patients presented mild, moderate, moderate/severe and severe depression and 17 (26.2%), 12 (18.5%) and 8 (12.3%) mild, moderate and severe anxiety. Patients with major depression had fewer years of formal education (• 8.7±3.6 vs • 11.6±3.4, p=0.004), worse quality of life (PsAQOL • 11.7±5.7 vs • 5.3±4.6, p<0.0001) and higher levels of anxiety (• 12.9±5.4 vs • 4.4±4.1, p=0.03). Patients with anxiety showed worse quality of life (PsAQOL • 8.8±5.7 vs. • 4.6±4.5, p=0.002) and functional capacity (HAQ-A • 1.09±0.7 vs • 0.67±0.7, p=0.02). Patients who did not achieve MDA had a higher prevalence of depression and anxiety (32.7% vs. 6.3%, p = 0.04 and 63.7% vs. 25%, p=0.003, respectively). In the multivariate analysis, adjusting for age, sex and disease duration, being in MDA was independently associated with less depression [β coefficient: -0.37, 95%CI -8.12-(-1.61), p=0.004] and anxiety [coefficient β -0.3, 95%CI -7.35-(-0.72), p=0.018].
Conclusion: The prevalence of major depression and anxiety disorders in this Argentinean cohort of PsA patients were 26.2% and 56.9%, respectively. Both disorders were associated with higher disease activity.
SECUKINUMAB IMPROVES AXIAL MANIFESTATIONS IN PSORIATIC ARTHRITIS PATIENTS WITH INADEQUATE RESPONSE TO NSAIDS: PRIMARY ANALYSIS OF PHASE III MAXIMISE TRIAL
Xenofon Baraliakos1, Laura C. Coates2, Laure Gossec3, Slawomir Jeka4, Antonio Mera5, Barbara Schulz6, Michael Rissler6, Ayan Das Gupta7, Chiara Perella6, and Effie Pournara6. 1Rheumatology Department, Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany, 2University of Oxford, Oxford, United Kingdom, 3Sorbonne Université and Hôpital Pitié-Salpêtrière, Paris, France, 4University Hospital Bydgoszcz no 2, CM UMK, Bydgoszcz, Poland, 5Division of Rheumatology, Instituto de Investigación Sanitaria-Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain, 6Novartis Pharma AG, Switzerland, 7Novartis Healthcare Pvt. Ltd., Hyderabad, India.
Objectives: Secukinumab (SEC) provides significant and sustained improvement in signs and symptoms of active psoriatic arthritis (PsA) and ankylosing spondylitis1. Evidence is limited on the efficacy of biologics in the treatment of PsA patients (pts) having axial manifestations that affect 30–70% of pts2, particularly as validated classification criteria for this subtype of PsA are not yet available; an effort to develop criteria is underway by ASAS/GRAPPA. MAXIMISE (NCT02721966) trial evaluated the efficacy and safety of SEC 300/150 mg in managing axial manifestations in PsA pts. Here, we report the primary analysis results at Week (Wk) 12.
Methods: This phase 3b, double blind, placebo (PBO)-controlled, multicenter 52-wk trial included pts aged ≥18 years with PsA (CASPAR criteria), clinician-diagnosed axial involvements, spinal pain VAS ≥ 40/100 and BASDAI ≥ 4 despite trial of at least two NSAIDs. Pts were randomized to subcutaneous (SC) SEC (300/150 mg) or PBO weekly for 4 wks and every 4 wks thereafter. At Wk 12, PBO pts were re-randomized to SC SEC 300/150 mg. The primary endpoint was ASAS20 response with SEC 300 mg at Wk 12. The key secondary endpoint was ASAS20 response with SEC 150 mg at Wk 12 after superiority of 300 mg was established. Data was analyzed using multiple imputation.
Results: Out of 498 pts randomized, 167, 165, and 166 pts received SEC 300 mg, 150 mg, and PBO, respectively; 476/498 (95.6%) pts completed Wk 12. The demographic and baseline disease characteristics were comparable across groups. Primary and key secondary endpoints were met; ASAS20 response rates at Wk 12 were 63.1% (SEC 300 mg; P< 0.0001) and 66.3% (150 mg; P< 0.0001) versus 31.3% (PBO). ASAS20 responses in pts using concomitant methotrexate (MTX) were 65.1% [300 mg], 67.3% [150 mg] versus 33.9% [PBO]; corresponding values in pts without concomitant MTX use were 60.5%, 64.4% versus 27.1%. The safety profile was similar across groups through Wk 12 with no new safety signals reported.
Conclusions: MAXIMISE is the first randomized controlled trial evaluating the efficacy of a biologic in the management of the axial manifestations of psoriatic arthritis. Secukinumab 300 mg and 150 mg provided rapid and significant improvement in ASAS20 responses through Week 12 in patients with psoriatic arthritis with axial manifestations and inadequate responses to NSAIDs.
1. Lubrano E and Perrotta FM. Ther Clin Risk Manag. 2016; 12:1587-92
2. Feld J, et al. Rheum Rev. 2018;14:363
RISK FACTORS ASSOCIATED WITH SEPSIS IN PATIENTS WITH RHEUMATIC AUTOIMMUNE DISEASES IN A THIRD LEVEL HOSPITAL IN ECUADOR
María Fernanda Soria Rosero1, María Eugenia Gómez Caballero2, and María Luciana Armijos Acurio3. 1Hospital General San Francisco Quito, Quito, Ecuador, 2Hospital Carlos Andrade Marín, Quito, Ecuador, 3Pontificia Universidad Católica del Ecuador, Quito, Ecuador.
OBJECTIVE: To examine the factors associated with the development of sepsis in patients with rheumatic autoimmune diseases admitted to Carlos Andrade Marín Hospital in Quito, Ecuador.
METHODS AND MATERIALS: This was a cross-sectional study that included adult patients (age >18 years old) with different rheumatic autoimmune diseases. 1657 had a diagnosis of Rheumatoid Arthritis (RA), 379 of Systemic Lupus Erythematosus (SLE), 133 of Ankylosing Spondylitis (AS), 141 of Sjögren's Syndrome (SS), and 84 of Overlap Syndrome (OS). The patients’ diagnosis were confirmed according to the "American College of Rheumatology" and / or the "European Rheumatology League" criteria. Among this population of patients, we included the ones that met sepsis-3 criteria. A univariate analysis of the population was carried out. Subsequently, the association of variables was analyzed through bivariate logistic regressions, and the variables with a statistically significant association (p<0.1) were assessed through a multivariate logistic regression model.
RESULTS: We found that of the total number of patients, 84.11% were female. The majority of the patients had RA (46.7%), 11.2% had OS, 2.8% SLE, 2.8% AS and 2.8% SS. In the bivariate analysis, the risk factors that demonstrated statistical significance were: prior infection (OR:1.62;CI:1.08-2.42;p=0.02), diagnosis of SLE (OR:3.58;CI:2.31-5.55;p<0.01), diagnosis of OS (OR:5.3;CI:2.73–10.5; p<0.01), admission to intensive care unit (OR:19.41;CI: 5.77–65.22;p<0.01), other infections during hospitalization(OR:2.36;CI:1.01–5.49;p=0.04), long-standing disease > 5 years (OR:3.42;CI:1.08- 2.42;p<=0.02), ≥2 pathogens (OR:3.67;CI:1.32–10.21;p<0.01) and chronic liver disease (OR:1.02;CI:0.9–11.75;p=0.02). In the multivariate analysis, the presence of a long-standing disease (>5 years) was shown to be statistically significant (OR:3.79; CI:1.53–9.36;p<0.01)
CONCLUSION: In this study, patients with SLE and OS had a higher risk of developing sepsis. The patients with more long-standing disease were more likely to develop septic shock.
CAUSES OF HOSPITALIZATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN A REFERENCE HOSPITAL IN THE AMAZON REGION
Natasha Santos1, Paulo Silva Filho2, and Glauce Lima1. 1Centro Universitário do Pará, Belém, Brazil, 2Hospital Universitário João de Barros Barreto, Belém, Brazil.
Background: Infection is the main cause of hospitalization among patients with Systemic Lupus Eythematosus (SLE), with a high morbidity and mortality rate, together with renal and neurological involvement.
Objective: To determine the causes of hospital admission and evaluation of disease activity and accumulated organ damage in patients with SLE.
Materials and methods: A cross-sectional, descriptive study performed through data collection from the medical records of 54 SLE patients admitted to a hospital in the Amazon region (Belém/Pará/Brazil) from January 2012 to December 2016. Epidemiological, clinical and therapeutic data were obtained. The SLEDAI and SLICC Damage indexes were applied to evaluate disease activity and organ damage, respectively. For statistical analysis Chi-square test and G Adherence test were used; a p value of p <0.05 was considered statistically significant.
Results: The causes of hospital admission for these SLE patients were: disease activity (57.4%), infection (44.4%), diagnosis (24.1%) and gestation risk (3.7%). The most common infection was in the urinary tract (42.6%). Among the causes related to infections, in addition to the infectious causes observed in the world literature, infections characteristic of the Amazon region were observed. Regarding the activity of the disease, it was predominantly of moderate degree (18 / 33.3%), with a predominance of renal (57.4%) and immunological manifestations (53.7%). Regarding the degree of damage, 70.4% did not present any permanent damage.
Conclusion: SLE is a disease of major morbidity and mortality, and it is necessary to know the epidemiological-clinical characteristic of patients in order to define a strategy to reduce hospitalization, optimize health resources and improve the quality of life of the population.
AUTOIMMUNE DISEASES RELATED TO IgG4 DEFICIENCY
Elisa Teresinha Hacbarth Freire1,2, Danielle R. Angilieri1,2, Leandro Parmigiani1,2, Marilia V. Carvalho Learth Cunha2, Monica Duarte Costa1,2, Taciana Paula S. Stacchini1,2, and Themis Torres1,2. 1Hacbarth Freire Serviços Médicos Ltda, São Paulo, Brazil, 2Hospital Prof Edmundo Vasconcelos, São Paulo, Brazil.
IgG subclass deficiencies have been described even in patients with normal total immunoglobulin levels. Some patients present with recurrent infections, but many have no clinical problems. IgG subclass deficiencies are generally due to abnormal B cell differentiation, and rarely to constant region genes homozygous deletions. We used to measure IgG subclasses in patients with autoimmune diseases, in our clinic, and here report three cases of severe IgG4 deficiency in patients with SLE.
Case 1: GXN, female, 40 years old, diagnosed with SLE 10 years before, with secondary Sjogren's syndrome, renal impairment progressing to hemodialysis in two occasions. We started treating her with rituximab, obtaining excellent clinical and laboratory responses, but the patient presented recurrent infections, often reactivating the disease. IgG4 and C4 deficiency have been identified, in addition to persistently elevated rheumatoid factor levels.
Case 2: TOV, female, 35 years old, diagnosed with SLE when she was 9 years old, with severe renal impairment. She presented recurrent seizures, worsening when she was 16 years old. We started to follow-up her because of thrombocytopenia, treated with prednisone and immunosuppressive drugs, evolving with renal, vascular, hematological, and cutaneous (bullous lupus) activity, and persistently low levels of IgG4. She continued with worsening of her conditions, infected bullous lesions, septic shock and major disease activity, with treatment-refractory pancytopenia (corticosteroid pulse therapy, hyperimmune gamma globulin and rituximab), renal failure, multiple organs failure and death.
Case 3: BRF, female, 58 years old. Followed because of cutaneous lupus since 2012, treated with antimalarial drugs, corticosteroids and methotrexate. During follow-up the patient presented with recurrent infections, leading to worsening of the cutaneous condition and responding only to high doses of corticosteroids. Treatment with azathioprine provided no clinical benefit. In this patient we detected persistently low levels of IgG4 subclass. Eventually the patient developed Sjogren syndrome.
Conclusion: In patients with complex autoimmune conditions and recurrent infections, besides deficiencies of complement components or their regulatory proteins, deficiencies of immunoglobulin subclasses should always be investigated, even with the levels of total immunoglobulin are normal.
CLINICAL CHARACTERISTICS AND OUTCOMES OF MEXICAN PATIENTS WITH POLYARTERITIS NODOSA
Eduardo Martín-Nares1, Susy Marcela Sánchez-Cubías1, Gabriela Hernandez-Molina1, Manuel Sedano-Montoya1, and Andrea Hinojosa-Azaola1. 1Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
Introduction: Polyarteritis Nodosa (PAN) is a primary necrotizing vasculitis that involves predominantly medium-sized vessels. Clinical characteristics and outcomes of PAN patients have been described mainly in Caucasian, Asian and Middle Eastern cohorts.
Objective: To describe the clinical characteristics and outcomes of Mexican Mestizo patients with PAN in a single center.
Methods: This was a medical records review study (1975-2018). We included patients with the diagnosis of PAN according to the ACR 1990 Criteria, EMEA Vasculitis Classification algorithm, and/or the definition from the Chapel Hill 2012 Consensus; we also included adult patients with childhood-onset PAN fulfilling the Ankara 2008 criteria (EULAR/PRES/PRINTO). We evaluated demographics, organ involvement, PAN phenotype, treatment and outcomes. Variables were compared against published UK and Turkish cohorts.
Results: We included 31 patients with PAN. Twenty were female (64.5%) with a median age at diagnosis of 28 years (IQR 16-42). Median time from first symptom to PAN diagnosis was 8 months (IQR 3-48). Seven (23%) had cutaneous, 23 (74%) systemic and 1 (3%) progressive systemic phenotype. Eleven (35%) patients had childhood-onset PAN. No cases of hepatitis B virus-related or monogenic PAN were found. Most common manifestations were musculoskeletal (71%), cutaneous (68%), constitutional (61%), peripheral nerve (39%) and gastrointestinal (29%). Ten of 15 (67%) patients with available angiography had evidence of microaneurysms. Biopsy was performed in 25 patients showing vasculitis in 22 (88%) of them. Median Birmingham Vasculitis Activity Score (BVAS) and Five Factor Score (FFS) at diagnosis were 9 (IQR 4-13) and 1 (IQR 0-1), respectively. Most patients were treated with glucocorticoids (94%). Other immunosuppressants used were azathioprine (68%), cyclophosphamide (45%) and methotrexate (35%). Twenty-four patients (80%) achieved complete and 6 (20%) partial remission at a median follow-up time of 30 (8-192) months. Median Vasculitis Damage Index (VDI) at last follow up was 1 (IQR 0-1). Nineteen (66%) patients experienced relapses. Childhood-onset patients had more frequently central nervous system (p=0.04) and gastrointestinal involvement (p=0.003) as well as microaneurysms (p=0.02); and lower C-reactive protein levels (p=0.03) compared to patients with adult-onset PAN. Mexican patients were more frequently female, had less frequency of kidney involvement and showed lower mortality rates than patients from the UK and Turkish cohorts.
Conclusion: Our cohort of PAN patients showed predominantly a systemic phenotype. Outcomes were generally good, with most patients achieving complete remission. Childhood-onset differed from adult-onset PAN in terms of clinical and serological characteristics, whereas clinical manifestations and outcomes may be different than the ones reported in other cohorts.
DIFFERENT IMMUNOPHENOTYPES CHARACTERIZED IGG4-RELATED DISEASE CLINICAL PHENOTYPES
Eduardo Martín-Nares1, Janette Furusawa-Carballeda1, Ángel Alexis Priego-Ranero1, Isela Chan-Campos1, Gladys Sulikey Herrera-Noguera1, Fidel López-Verdugo1, and Gabriela Hernandez-Molina1. 1Department of Immunology and Rheumatology, Instituto Nacional De Ciencias Médicas y Nutrición Salvador Zubirán, México City, México.
Introduction: Patients with IgG4-related disease (IgG4-RD) can be classified in clinical phenotypes which differ in terms of demographics, clinical and serological features. Whether there are also differences in the immunophenotype of each phenotype is unknown.
Objective: To characterize the immunophenotype of IgG4-RD patients according to their clinical phenotype.
Methods: We included consecutive patients with a diagnosis of IgG4-RD according to the Comprehensive Diagnostic Criteria for IgG4-RD who were cared for at our Institution from Aug 2018 to Nov 2019. Healthy subjects were included as controls. We obtained peripheral blood for isolation of peripheral mononuclear cells and through negative selection, CD4+ memory T cells were obtained. We determined the percentage of the following cell subsets by flow cytometry:
1. Th2 (CD4+/CD45RO+/CD14-/IL-4+; CD4+/CD45RO+/CD14-/IL-13+, CD4+/CD45RO+/CD14-/IL-5+);
• CD4+IL-21 T cells (CD4+/CD45RO+/CD14-/IL-21+);
• CD4+ cytotoxic T cells (CTLs) (CD4+/CD45RO+/SLAMF7+/IL-1β+/TGF-β1+);
• Th9 (CD3+/CD4+/ CD45RO+/IL-9);
• T follicular helper cells (Tfh) (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+);
• Tfh1 (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/IFN-γ+);
• Tfh2 (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/IL-4+);
• Tfh17 (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/IL-17+);
• Tfr (CD4+/CD45RO+/CCR7-/ICOS+/CCCR5+/Bcl6+/Foxp3+);
• Tregs (CD4+/CD25hi/CD127-/Foxp3+);
• Tr1 (CD4+/CD25low/Foxp3-/IL-10+);
• Th3 (CD4+/CD25-/Foxp3-/TGF-β1+);
• Bregs (CD19+/CD24hi/CD38hi/IL-10+);
• Plasmocitoid dendritic cells (pDC) (CD86+/CD163hi/IL-10+);
• M1 macrophages (CD86+/CD127+/TNF-α+);
• M2 macrophages (CD163+/CD14+/TGF-β1+/IL-33+).
Results: We recruited 43 patients with a mean age of 52.3±16.4 years, 48.8% were male. Twelve controls were included. Eight (18.6%) patients belong to the pancreato-hepatobiliary, 7 (16.3%) to the retroperitoneal-aorta, 16 (37.2%) to the head and neck limited and 12 (27.9%) to the Mikulicz/Systemic phenotypes. Twenty-two patients (51.2%) had active disease. The percentages of all cell subsets were statistically higher in patients vs controls, with the exception of Tr1 cells. The percentages of the following cell subsets were different among clinical phenotypes: Th2 (CD4+/IL-4+) (p=0.029), Th2 (CD4+/IL-5+) (p=0.047), CD4+ CTLs, (p=<0.001), Tfh17 (p=0.005), Tregs FOXP3+ (p=0.008), Th3 (p=0.02), Bregs (p=0.005) and pDC IL-10 (p=0.016). In a sensitive analysis including only the 22 patients with active disease, the same cell subsets remained significant and we also observed differences in Tfh1 (p=0.03), Tfh2 (p=0.009), Tr1 (p=0.034), and M1 macrophages (p=0.03). Patients with active IgG4-RD had higher proportions of Tfh (p<0.001), Tfh17 (p<0.001), Tr1 (p=0.001), Th3 (p=0.01), pDC IL-10 (0.005) and M1 macrophages (p=0.017). There were no differences according to the presence of atopy or immunosuppressive treatment at recruitment.
Conclusion: Our study showed that the clinical heterogeneity of IgG4-RD might be driven by the participation of different immune cell subsets.
SCREENING OF LUNG INVOLVEMENT IN PATIENTS WITH EARLY RA. A MULTICENTRIC CROSS SECTIONAL STUDY
Federico Lujan Benavidez1, Martín Riopedre1, Dario Mata1, Gonzalo Rodriguez1, Alejandro Benitez1, Hernan Molina1, Malena Viola1, Eliana Blanco1, Cecilia Garbarino1, Francisco Paulin2, Fabian Caro2, Martín Fernandez2, Laura Alberti2, Anastasia Secco3, Patricia Sasaki2, Agustina Caceres3, Omar Carballo4, Fernanda Ingenito4, Santiago Rossi5, and Maria Celina de La Vega1. 1Ceim, Lanus, Argentina, 2Hospital Ferrer, Ciudad Autónoma de Buenos Aires, Argentina, 3Hospital Bernardino Rivadavia, Ciudad Autónoma de Buenos Aires, Argentina, 4Hospital Durand, Ciudad Autónoma de Buenos Aires, Argentina, 5Centro de Diagnóstico Rossu, Ciudad Autónoma de Buenos Aires, Argentina.
Introduction: Rheumatoid arthritis (RA) affects 0.4-1.3% of the general population. It can affect lungs in different ways, with interstitial lung disease (ILD) being the most severe. Clinically evident ILD has been reported in 10-42% of patients, with a great impact in prognosis.
Objective: To identify the prevalence of lung involvement in early RA patients (ERA) without previous known lung disease and describe the association between high resolution computed tomography (HRCT), lung functional tests (LFT) and clinical findings.
Materials and Methods: Cross sectional multicentric study. We included ERA patients (1 year or less since diagnose) consecutively. Patients with previous RA related lung disease or biologic/targeted synthetic DMARD treatment were excluded. HRCT, immunological tests (rheumatoid factor, anti-CCP, ANA), LFT and clinical evaluation were performed.
Results: We included 74 patients, 63 (85,1%) women, mean (SD) of 47 (17,7) years. Thirty-seven patients (50%) were current or former smokers. Abnormal findings in HRCT were found in 62 patients (88,6%): ILD in 6 (8,6%), airway involvement in 40 (70%) and emphysema in 7 (10%). Ten patients (13,5%) had abnormal auscultation (2wheezing, 2 rhoncus, and 6 crackles). Six patients (8,1%) had digital clubbing. Regarding immunological tests, 54/61 (88,5%) patients were positive for Anti CCP antibodies, and 53/61 (86,9%) were positive for RF. We compared features of patients with findings related to RA in HRCT (interstitial and/or airway) with those without them. We found no differences in the mean (SD) DAS-28 [4,74 (1,38) vs 4,32 (1,39); p= 0,27]. The prevalence of anti- CCP was not higher in patients with abnormal HRCT [38/44 (86,3%) vs 16/17 (94,1%); p=0,39]. Patients with abnormal HRCT were older [median (IQR) 50,5 years (44,5-59,5) vs 43 years (32-51); p=0,008) and showed higher ESR values [mean (SD) 39,09 (24,03) vs 27,38 (17,6); p= 0,043]. Abnormal physical examination or dyspnea (class 2 mMRC or higher) was significantly associated with HRCT abnormalities [26 (50%) vs 3 (13,6%); p=0.003) and the presence of ILD on HRCT was significantly associated with crackles on auscultation [4/68 (6,25%) vs 2/6 (33,33%); p 0,023].
Conclusion: This study shows a high prevalence of lung involvement in ERA patients of less than 1 year from diagnosis. Also, we showed a significant association between HRCT and physical examination findings. These data highlight the importance of the clinical examination in RA patients. More studies with larger samples and longitudinal follow up are needed to confirm and complete our results.
TREATMENT OF SYSTEMIC AND REFRACTORY ADULT-ONSET STILL’S DISEASE WITH TOFACITINIB. EFFICACY OF JAK/STAT PATHWAY INHIBITION
Sergio Aguilera1, Diego Rivera2, and María-José Barrera3. 1Clínica Indisa, Santiago, Chile, 2Facultad de Medicina, Universidad de Chile, Santiago, Chile, 3Facultad de Odontología, Universidad San Sebastián, Santiago, Chile.
Introduction: Adult-onset Still's disease (AOSD), with an acute and aggressive systemic phase can lead to chronic and destructive arthritis. These patients often have a limited response to disease-modifying anti-rheumatic drugs (DMARDs) and chronic use of corticosteroids (CS). Although biological treatments can be effective (anti-IL-1R -IL-6R, and -TNF-α antibodies), their use may be limited by loss of efficacy (neutralizing antibodies) and non-response. On the other hand, JAK inhibitors, which block numerous proinflammatory cytokines, and which are effective in rheumatoid arthritis could be useful in refractory AOSD.
Objectives: We evaluated the use of tofacitinib in two recalcitrant cases of AOSD, who previously showed a partial response to DMARDs, GC, and adalimunab therapy. In addition, we determined if tofacitinib inhibits the JAK/STAT pathway activation, in a 3D in vitro model that simulating innate immune system cells exposed to pro-inflammatory cytokines.
Methods: We described two cases of men (case 1 of 18 and case 2 of 31 years of age) who were hospitalized for high spiking fevers, evanescent rash, sore throat, synovitis and adenopathies. Laboratory studies revealed neutrophilic leukocytosis, high HSV and CRP, hyperferritinemia and absence of autoantibodies and infections. Both showed a moderate response to high doses of methylprednisolone, methotrexate (MTX) and adalimunab (case 2 only). They were treated with tofacitinib (10 mg/day) associated with MTX (20 mg weekly). Also, 3D-acini of HSG cells were incubated with 10 ng/mL recombinant IL-6 or IFN-γ (with/without tofacitinib) to measure MCL-1 and IL-6 mRNA levels by qPCR or STATs activation by Western blot.
Results: In both cases there was no evidence of major adverse effects, showing a gradual improvement in systemic manifestations and arthritis. Case 2, evolved into a chronic erosive joint form, which was inactivated with tofacitinib. On the other hand, case 1 achieved complete remission. Follow up of these patients off tofacitinib, has been 6 months in case 1, while case 2 continues with tofacitinib monotherapy of, with no evidence of activity or adverse effects.
In vitro studies showed that tofacitinib inhibited JAK/STAT pathway activation in response to cytokines. It also reverses the induction of IL-6 and MCL-1 expression stimulated by IL-6.
Conclusions: Our cases showed the efficacy and safety of JAK/STAT pathway inhibition in refractory cases of AOSD. Tofacitinib may be another alternative to biologics use due to the inhibition of several proinflammatory cytokines responsible for clinical manifestations. These data may support other clinical trials for the use of JAK/STAT pathway inhibitors.
PATIENT BELIEFS AND PERCEPTIONS OF METHOTREXATE FOR THE TREATMENT OF RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS
W. Benjamin Nowell1, Elaine Karis2, Kelly Gavigan1, Laura Stradford1, Scott Stryker2, Shilpa Venkatachalam1, Greg Kricorian2, and Jeffrey R. Curtis3. 1Global Healthy Living Foundation, Upper Nyack, United States, 2Amgen Inc., Thousand Oaks, United States, 3University of Alabama at Birmingham, Birmingham, United States.
Objectives: Methotrexate (MTX) is a frequently used therapy in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) due to its beneficial effects in both populations. Despite the well-known benefits of MTX, it is associated with a number of potential side effects and tolerability issues including nausea and fatigue, gastrointestinal toxicity, skin reactions, headaches, mouth sores and more serious, though rare, side effects. The combined risks of rare but potential adverse events along with frequently reported side effects may add to patient burden of dealing with a chronic disease. Currently, there is a gap in patient-centered studies focusing on patients’ experience with MTX and how this relates to adherence and consequently patient outcomes. The purpose of this ongoing study is to examine patient beliefs and perceptions relating to methotrexate therapy for the treatment of RA and PsA.
Materials and Methods: Adult US patients in the ArthritisPower registry with self-reported RA or PsA taking or previously taking MTX were invited to participate in the survey via email invitation. Participants (pts) were either current or past users of MTX who completed a brief online survey. Descriptive statistics were conducted on data collected to date.
Results: As of December 2019, the survey had been completed by 628 pts of whom 77.4% were living with RA and 30.3% with PsA, not mutually exclusive. Mean (SD) age was 53.8 (11.5) years, 88.2% female, 92.2% White, with mean BMI 32.0 (7.8). Mean duration of MTX treatment among current users was 4.9 (6.1) years. Among respondents, 322 (51.3%) were currently taking oral MTX and 306 (48.7%) had taken it previously but stopped. The majority of pts reported experiencing side effects on MTX: 195 (60.6%) among current users of MTX, 245 (80.1%) among those who previously discontinued MTX. Fatigue was the most common symptom among both groups, while nausea, abdominal pain, and flu-like feeling were more common among discontinuers. When asked specifically, 67.1% of current users and 70.3% of discontinuers stated that they experienced fatigue within a day of their MTX dose. Nevertheless, among those currently taking MTX, most (65.6%) felt that MTX protects them from becoming worse and 47.8% agreed that their life would be impossible without MTX.
Conclusion: Although people living with RA or PsA acknowledge the importance of taking MTX to manage their condition, the majority of patients experience side effects, such as fatigue and nausea that they attribute to MTX.
CARDIOVASCULAR RISK FACTORS IN RHEUMATOID ARTHRITIS
Araceli Chico Capote, Franklin Uguña Sari, and Tania Hidalgo Costa. 1Hospital Hermanos Ameijeiras, Havana, Cuba.
Introduction: Rheumatoid arthritis (RA) is itself a risk factor for the development of cardiovascular diseases as a result of the interaction between traditional cardiovascular risk factors (CVR) and those associated with the state of systemic inflammation.
Objective: Describe the factors of CVR and evaluate its possible association with cardiovascular risk in patients with RA.
Methods: Descriptive and cross-sectional study in 200 patients with a diagnosis of RA. Traditional and non-traditional CVR factors were recorded as variables; Patients diagnosed with a previous cardiovascular disease were excluded.
Results: Female sex predominated (90.0%), average age of 56.9 years ± 10.4 with disease duration time of 9.6 years ± 8.6. The most frequent traditional risk factors were arterial hypertension (54, 0%) and overweight (38.5%) and non-traditional, positive rheumatoid factor (70%), disease activity index 28 joints-C-reactive protein (DAS 28-CRP) moderate-high (58%) and disease duration time> 10 years (33%). The 10-year CVR by Framingham scale was low in62.5% and moderate-high in 37.5%. Arterial hypertension, Diabetes, dyslipidemia and smoking were associated with moderate-high CVR (p <0.05).
Conclusions: Most patients with RA presented low cardiovascular risk and there was an association between some traditional CVR factors with respect to moderate and high CVR.
CLINICAL CORRELATES OF FIBROMYALGIA IN PUERTO RICANS WITH PRIMARY SJÖGREN’S SYNDROME
Ariana González-Meléndez1, Patricia Jordán-González1, Ricardo Gago-Piñero1, Noemí Varela-Rosario1, Naydi Pérez-Ríos1, and Luis Vilá1. 1University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico.
Objective: Several symptoms such as tiredness, arthralgias, myalgias and sicca symptoms occur both in primary Sjögren’s syndrome (pSS) and fibromyalgia (FM). However, the clinical correlates of patients with coexistent pSS and FM are not well documented. Thus, we aimed to determine the factors associated with FM in a cohort of Hispanics from Puerto Rico with pSS.
Methods: A cross-sectional study was conducted 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, pSS clinical manifestations, autoantibodies, comorbidities, disease activity (per EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]), disease damage (per Sjögren’s Syndrome Disease Damage Index [SSDDI]) and, pharmacologic treatment were studied in pSS patients with and without FM. FM was ascertained using the 1990 ACR classification criteria. Patient characteristics were analyzed by bivariate and multivariate analyses adjusted for age, sex and disease duration.
Results: In total, 100 patients were studied, 94% were female. The mean (standard deviation [SD]) age was 53.6 (6.2) and the mean (SD) disease duration was 5.8 (4.2) years. Sixteen patients (16.0 %) had FM. In the bivariate analyses, patients with FM were less likely to have lymphopenia (6.3% vs. 32.5%, p=0.036), but more likely to have dyslipidemia (62.5% vs. 28.6%, p= 0.018), anxiety (50.0% vs. 20.2%, p=0.023), sleep disturbances (50.0% vs. 8.3%, p= <0.001), headaches (18.8% vs. 3.6%, p=0.050) and antidepressants exposure (68.8% vs. 21.4%, p= <0.001) than those without FM. No differences were found for smoking, exercise, body mass index, arthralgias, serologic tests, disease activity, disease damage, and exposure to nonsteroidal anti-inflammatory drugs, corticosteroids, hydroxychloroquine or immunosuppressive agents. In the multivariate analysis, dyslipidemia (OR= 3.92, 95% CI 1.24-12.40), anxiety (OR= 5.32, 95% CI 1.53-18.47), sleep disturbances (OR= 10.21, 95% CI 2.72-38.23), headaches (OR= 7.59, 95% CI 1.24-46.36), and antidepressants use (OR= 8.90, 95% CI 2.60-30.50) retained significance.
Conclusion: In this group of Puerto Ricans with pSS, 16% had FM. Clinical associations of patients with coexistent pSS and FM were more likely attributed to FM (anxiety, sleep disturbances, headaches, and antidepressants use). Conversely, FM did not appear to have an impact on the severity of pSS as no differences were observed for pSS manifestations, disease activity, damage accrual, or pharmacologic agents between patients with and without FM.
A PHASE 3 CLINICAL PROGRAM OF THREE, RANDOMIZED, DOUBLE-BLIND, PLACEBO- AND COMPARATOR-CONTROLLED STUDIES TO ASSESS THE EFFICACY AND SAFETY OF OTILIMAB IN RA: STUDY DESIGN AND METHODOLOGY
Mark Genovese1, Peter C. Taylor2, Maarten Boers3, Vibike Strand1, Didier Saurigny4, Katherine Davy4, Anubha Gupta4, Stephen Harrison4, Rod Hepburn4, Jatin Patel5, Mark Layton4, Millie Wang4, and Roy Fleischmann6. 1Stanford University, Stanford, United States, 2University of Oxford, Oxford, United Kingdom, 3Amsterdam University Medical Centers, Amsterdam, The Netherlands, 4GlaxoSmithKline, Stevenage, United Kingdom, 5GlaxoSmithKline, Uxbridge, United Kingdom, 6Metroplex Clinical Research Center and University of Texas Southwestern Medical Center, Dallas, United States.
Objectives: Otilimab (GSK3196165) is a human monoclonal antibody that inhibits GM-CSF and has shown efficacy in Phase 2 randomized controlled trials (RCTs) in patients with RA. The contRAst Phase 3 clinical program comprises 3 ongoing multicenter RCTs that will assess the efficacy and safety of otilimab in patients with moderate to severely active RA.
Methods: contRAst-1 (N=1500–1700) and contRAst-2 (N=1500–1800) are the first RA trials to include the oral targeted synthetic (ts) DMARD tofacitinib as a comparator with a 52-week duration (contRAst-1: otilimab vs tofacitinib or placebo, plus MTX; contRAst-2: otilimab vs tofacitinib or placebo, plus conventional synthetic [cs]DMARDs). ContRAst-3 (N=525–600) is a 24-week trial that will assess otilimab vs the anti-IL-6 monoclonal antibody sarilumab or placebo, plus csDMARDs. The program will enroll patients with an inadequate response to MTX (contRAst-1), cs/bDMARD (contRAst-2) or bDMARD-IR and/or JAKi-IR (contRAst-3). Otilimab dose selection was based on pharmacokinetic/pharmacodynamic modelling and simulation of Phase 2 data. Patients will be randomized 6:6:3:1:1:1 (contRAst-1 and -2) or 6:6:6:1:1:1 (contRAst-3) to weekly subcutaneous otilimab 150 mg or 90 mg, active comparator (approved dose and route), or placebo (3 arms). At Week 12 all patients in the placebo arms will switch to active treatment, randomized equally to the two otilimab doses and active comparator. Primary endpoint: proportion of ACR20 responders at Week 12. Secondary endpoints include: health assessment questionnaire disability index and clinical disease activity index (CDAI); CDAI was chosen based on findings from the BAROQUE Phase 2 study to provide an alternative to DAS28(CRP), which is heavily influenced by changes in CRP. Radiographic changes, patient-reported outcomes (including pain), and safety will also be assessed. The primary endpoint will be compared separately between each otilimab dose and the pooled placebo group up to Week 12, with additional comparisons between the original randomized otilimab groups and tofacitinib at Weeks 12, 24, and 52. The analysis will include a comprehensive safety evaluation of the two otilimab doses and a comparison vs an oral tsDMARD over 1 year, and vs bDMARD over 24 weeks.
Conclusions: The novel aspects of the contRAst program plus a wide geographical coverage (USA, Central and South America, western and eastern Europe, Asia [including Japan and China]) will provide a robust global dataset. Recruitment is ongoing.
Studies funded by GSK (201790 [NCT03980483]), 201791 [NCT03970837], 202018 [NCT04134728]). Medical writing support provided by Clare Slater, PhD CMPP, of Fishawack Indicia Ltd, UK, funded by GSK.
THE ANTIPHOSPHOLIPID ANTIBODIES REGISTRY OF THE ARGENTINEAN SOCIETY OF RHEUMATOLOGY (GESAF-SAR): BASELINE DATA OF THE FIRST 162 PATIENTS
Sabrina Porta1, Romina Nieto3,2, Rosa Serrano2, Veronica Savio4,5, Luis Lema6, Carla Maldini6, Silvia Perés1, Pia Izaguirre1, Verónica Bellomio7, Maria Lilia Leguizamón7, Monica Sacnun3, Adrián Estevez8, Alejandra Avalo8, Maira Etcheverri8, Maria Noelia Antoniol9, Carlos Perandones9, Cecilia Goizueta10, Victoria Lobo10, Carla Gobbi11, Pablo Artesana11, Natalia Cucchiaro12, Florencia Vivero13, Mariela Bastita13, Verónica Saurit14, Nadia Riscanevo14, Cecilia Pissoni15, Maria Laura De la Torre15, Maximiliano Machado Escobar16, Maria Constansa Danielsen17, Graciela Remondino18, Verónica Neman18, Nadia Benzaquen19, Alejandra Babini20, Carmen Funes20, Karen Roberts2, Débora Guaglianone3, Graciela Gómez21, Nicolás Pérez21, Horacio Berman22, Paula Alba4,5, and Guillermo Pons Estel2. 1Htal Ramos Mejia, Ciudad Autónoma de Buenos Aires, Argentina, 2Centro Regional de Enfermedad Autoinmunes y Reumáticas, Rosario, Argentina, 3Hospital Provincial de Rosario, Rosario, Argentina, 4Hospital Córdoba, Córdoba, Argentina, 5Hospital Materno Neonatal, Córdoba, Argentina, 6Instituto Modelo de Cardiología, Córdoba, Argentina, 7Hospital Ángel C Padilla, San Miguel de Tucumán, Argentina, 8Hospital El Cruce, Florencio Varela, Argentina, 9FLENI, Ciudad Autónoma de Buenos Aires, Argentina, 10Sanatorio 9 de Julio, San Miguel de Tucumán, Argentina, 11Sanatorio Allende, Córdoba, Argentina, 12Hospital Señor del Milagro, Salta, Argentina, 13Hospital Privado de la Comunidad, Mar del Plata, Argentina, 14Hospital Privado Universitario de Córdoba, Córdoba, Argentina, 15CEMIC, Ciudad Autónoma de Buenos Aires, Argentina, 16Instituto de Maternidad y Ginecología Nuestra Señora de las Mercedes, San Miguel de Tucumán, Argentina, 17Hospital Regional Dr. Ramón Carrillo, Santiago del Estero, Argentina, 18Consultorios La Rioja, Ciudad Autónoma de Buenos Aires, Argentina, 19Sanatorio Diagnóstico, Santa Fe, Argentina, 20Hospital Italiano de Córdoba, Córdoba, Argentina, 21Instituto de Investigaciones Médicas Alfredo Lanari, Ciudad Autónoma de Buenos Aires, Argentina, 22Centro Médico Privado de Reumatología, San Miguel de Tucumán, Argentina.
Objective: Antiphospholipid antibodies registry of the Argentinean Society of Rheumatology (GESAF-SAR) was created to study long-term disease characteristics and outcomes in persistently antiphospholipid antibody (aPL)-positive patients. The objective was to report baseline demographic, clinical, laboratory and treatment characteristics of aPL-positive patients enrolled in the registry.
Materials and Methods: GESAF-SAR is a multicenter, multidisciplinary and longitudinal study. Thirty centers from Argentina participated. Data collection was performed by review of medical records and interview with individuals/patients, after signing an informed consent. A web-based data capture system (ARTHROS) was used. Inclusion criteria: aPL with at least one positive determination of Lupus Anticoagulant (LAC) and/or positive Anticardiolipin Antibodies (aCL) and Anti-βeta 2 Glycoprotein I (aβ2GLPI) IgG and IgM greater 40 or positive aCL and/or aβ2GLPI with levels 20-40 GPL or MPL (at least two determinations) separated by 12 weeks. Patients were followed every 12±3 months. Descriptive cross-sectional analysis of data collected from May to October 2019 was performed.
Results: Overall 162 patients were enrolled, 139 (86%) were women with a mean age at entry of 40.3 years (SD 12.9); 76 (47%) patients were Mestizo, 72 (44%) Caucasians and 14 (9%) others. The socioeconomic level was Medium-Low in 47 patients (29%), Medium in 58 (36%) and Medium-High in 25 (15%). Seventy-four patients (46%) met classification criteria for Primary APS, 37 (23%) were APS associated with autoimmune disease and 2 (1%) were catastrophic APS (CAPS). Of the 111 APS patients, 50 (45%) presented thrombotic manifestations, 44 (40%) obstetric and 16 (15%) both. Forty-nine patients (30%) did not meet classification criteria of APS. A total of 40 (24.7%) venous events, 34 (21%) arterial, 70 (43.2%) obstetric morbidity and 55 (34%) non-criteria manifestations were recorded. Seventy-seven women presented at least one pregnancy with a total 265 gestations, resulting in 104 (39%) live births. Of all gestations, 80 (30%) were miscarriages <10 weeks, 53 (20%) premature births, 42 (16%) placental insufficiency, 24 (9%) preeclampsia and only 2 (1%) eclampsia. Based on aPL profile, 88 (54%) were positive for LAC, 110 (68%) aCL and 74 (46%) for aβ2GLPI. Regarding treatments, 117 (72%) patients received Aspirin, 71 (43.8%) oral anticoagulation, 53 (32.7%) prophylactic heparin, 46 (28.4%) therapeutic heparin, 92 (56.8%) hydroxychloroquine.
Conclusions: In our multi-center Argentinean aPL-positive cohort, at baseline: a) 30% of patients did not meet classification criteria of APS, b) 46% met classification criteria for Primary APS, c) one-fourth were APS associated with autoimmune disease, d) 45% presented thrombotic manifestations, e) the most frequent obstetric morbidity were miscarriages <10 weeks. Future longitudinal analysis of GESAF-SAR Registry will help clarify the risk profiles of aPL in Argentina.
CIRCULATING CELL-FREE DNA AND DNASE I Q222R GENETIC VARIANT AS POTENTIAL BIOMARKERS IN SYSTEMIC LUPUS ERYTHEMATOUS
Sabrina Porta1, Silvia Perés2, Federico Aranda2, Maria Fernanda Egüez Del Pozo1, Mauro Moiana2, Ana Lucero2, Ana Canizares1, Marina Micelli1, Eduardo Kerzberg1, and Gabriela De Larrañaga2. 1Hospital Gral de Agudos Dr. J.M. Ramos Mejia, Ciudad Autónoma de Buenos Aires, Argentina, 2Hospital de Infecciosas Dr. F. J. Muñiz, Ciudad Autónoma de Buenos Aires, Argentina.
Introduction: Excessive formation and/or insufficient clearance of neutrophil extracellular traps (NETs) have been reported in systemic lupus erythematous (SLE) and which could be associated with an increased disease activity. Therefore, increased levels of circulating cell-free DNA (cfDNA) could potentially be a disease activity biomarker. The insufficient clearance of NETs could mainly be due to a decreased DNAse I activity that could result from single-nucleotide polymorphisms in its gene, like the genetic variant Q222R.
Aims: To study cfDNA plasmatic levels and the distribution of the DNAseI-Q222R genetic variant to evaluate their predictive value both in the development and evolution of SLE in an Argentinian cohort.
Methods: We studied 54 SLE patients [(32 years (23-40), female 89%] who fulfilled the ACR criteria for SLE (2012), 95% were treated with hydroxychloroquine and 52% with prednisone. The control group consisted of 86 unrelated healthy subjects from the general population who had no personal history of chronic inflammatory and/or autoimmune diseases [(30 years (25-39), female 60%]. cfDNA levels were measured with the Quant-iT™ PicoGreen® dsDNA Assay Kit, (Thermo Fisher Scientific), and the DNAseI-Q222R genotyping was assessed by PCR-RFLP. The statistical analysis was performed using the SPSS statistical package (Version 23.0 IBM SPSS Statistics).
Results: cfDNA plasmatic levels were found to be significantly higher (p<0.005, Mann-Whitney test) in SLE patients (1,22 ng/ul (1,06-1,42) with regard to the controls 1,00 ng/ul (0,92-1,06). However, no differences were found among SLE patients grouped according to clinical manifestations, laboratory, damage and disease activity.
The distribution of the DNAseI-Q222R genotypic frequencies in SLE patients and controls did not show significant differences (p=0.78) even under different models of allelic dominance. Due to the small sample size, no analysis of its distribution within SLE groups could be performed.
Conclusion: While SLE patients had higher levels of cfDNA than controls, we did not find cfDNA increased levels in patients with lupus nephritis or other clinical manifestation of SLE. Therefore, it would not be useful as a biomarker to identify risk groups. As almost all of our patients were being treated with hydroxycholoroquine, which inhibits NETosis at physiologic concentrations, we consider that these results highlight a limitation of cfDNA as a potential biomarker in SLE patients under treatment. On the other hand, DNAseI-Q222R genetic variant was not found to be associated with the onset of SLE.
ASSESSMENT OF SIX CARDIOVASCULAR RISK CALCULATORS IN MEXICAN PATIENTS WITH PSORIATIC ARTHRITIS
Dionicio Angel Galarza Delgado1, Jose Ramon Azpiri Lopez2, Iris Jazmin Colunga Pedraza1, Diana Elsa Flores Alvarado1, Octavio Ilizaliturri Guerra1, Paola Fernanda Frausto Lerma1, Mayra Alejandra Reyes Soto1, Alejandra Perez Villar1, and Itzel Corina Zarate Salinas2. 1Rheumatology Department, Hospital Universitario “Dr Jose Eleuterio Gonzalez”, UANL, Monterrey, México, 2Cardiology Department, Hospital Universitario “Dr Jose Eleuterio Gonzalez”, UANL, Monterrey, México.
Objectives: Patients with psoriatic arthritis (PsA) have an increased risk of cardiovascular (CV) morbidity and mortality. CV risk evaluation is performed by CV risk calculators such as the Framingham Risk Score (FRS) using lipids, FRS using body mass index (BMI), Reynolds Risk Score (RRS), QRISK3, and an algorithm developed by the American College of Cardiology and the American Heart Association in 2013 (ACC/AHA). However, these models underestimate CV risk in PsA patients. We aimed to compare these six CV risk scales in PsA patients (FRS Lipids, FRS BMI, RRS, ACC/AHA 2013, QRISK3, JBS3).
Methods: Cross-sectional study, which included 91 PsA patients, aged 40-75, who fulfilled the CASPAR classification criteria. Predicted CV risk global comparison was performed using the Friedman test, considering a p value ≤ 0.05 as statistically significant. Individual comparisons were made using the Wilcoxon signed-rank test, and a p value ≤ 0.05 was considered statistically significant.
Results: A total of 91 patients were included: Median of age was 53 (46-61) years, 53 (58.2%) were female. Disease duration median was 4 (2-8) years. Concerning cardiovascular risk factors, 17 (18.7%) had type 2 Diabetes Mellitus, 33 (36.3%) had hypertension, 37 (40.7%) had dyslipidemia, 33 (36.3%) had a BMI >30kg/m2, and 20 (22%) were active smokers. Global comparison of predicted CV risk was significatively different on the Friedman test (p≤0.001). Median values of predicted 10-year CV risk were 5% (1.15-12.5) for FRS Lipids; 11.4% (4.25-20.85) for FRS BMI; 3% (1-8) for RRS; 6.5% (1.9-16.55) for ACC/AHA 2013; 5-4% (2-11.3) for QRISK3; and 5% (2-13) for JBS3 (Table 1). Using the Wilcoxon signed-rank test, FRS Lipids show no difference when compared to QRISK3 and JBS3 (p=0.180 and p=0.414, respectively); RRS was not different from QRISK3 (p=0.157); and the comparison between QRISK3 and JBS3 demonstrated no difference (p=0.059).
Conclusions: CV risk calculators show discrepancy between them and cannot be used indistinctly in PsA-patients.
ROC ANALYSIS OF ADIPOKINES (ADIPONECTIN, RESISTIN, ADIPSIN, VASPIN AND LEPTIN) IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS
Yany Magali Chamorro-Melo1, Consuelo Romero-Sánchez1,5, Omar Javier Calixto3, Juan-Manuel Bello-Gualtero1,2, Wilson Bautista-Molano2,5, and Adriana Beltrán-Ostos4. 1Rheumatology and Immunology Department Hospital Militar Central, Bogotá, Colombia, 2Clinical Immunology Group Hospital Militar Central, School of Medicine, Universidad Militar Nueva Granada, Bogotá, Colombia, 3Internal Medicine Department Hospital Militar Central, Universidad Militar Nueva Granada, Bogotá, Colombia, 4Research and Teaching Department Hospital Militar Central, Bogotá, Colombia, 5Universidad El Bosque, Cellular and Immunology Group /InmuBo, Bogotá, Colombia.
Background: Early rheumatoid arthritis (eRA) is a period in the disease in which all kind of interventions (e.g. pharmacological, physical, education and metabolic) may impact positively the course of this condition overtime. The role of adipokines in the mechanism of autoimmune diseases is supported by studies of their immunomodulatory effect on synovial tissue, cartilage, bone, and immune cells. Therefore, the monitoring of serological biomarkers may become relevant and useful. The objective of this study was to evaluate the performance of adipokine-profile in patients with eRA, in order to define cut-off points for the analysis of these biomarkers.
Methods: A cross sectional study was conducted. Patients with eRA according to the ACR/EULAR 2010 criteria with a disease duration less than two-years and healthy controls matched by age and gender were included. A complete medical history was obtained. Adipokines levels (adiponectin, resistin, adipsin, measured by Luminex technology and Enzyme-linked immunosorbent assay (vaspin and leptin) were measured. Additionally, serum markers of RA such as rheumatoid factor, erythrocyte sedimentation rate, C reactive protein, and anticitrullinated protein antibodies-APCA IgG/IgA were measured. Disease activity was assessed using DAS28-CRP, DAS28-ESR and SDAI. A cut-off analysis of serum levels was performed based on an AUC curve with subsequent calculation of sensitivity, specificity, and likelihood ratios.
Results: In total 51 cases and 51 controls were included, 41% women in both groups. Table 1 includes values obtained from adipokines. The ROC curve analysis identified for leptin a cut-off point ≥0.58pg/mL with sensitivity (76.5%), specificity (74.5%), and positive likelihood (3.0). For vaspin ≥96.2pg/mL with sensitivity (72.0%), specificity (62.5%) and positive likelihood (1.9). For adipsin ≥9529pg/mL with sensitivity (39.2%), specificity (86.3%) and positive likelihood (2.9). Adiponectin ≥35518pg/mL with sensitivity (66.7%), specificity (51%), and likelihood positive (1.4). Finally, for resistin a value of ≥48.3pg/mL with sensitivity (58.8%), specificity (52.9%), positive likelihood (1.25) was obtained.
Conclusions: Cut-off points for adipokines levels in a population with eRA were determined. To our knowledge, the present study is the first in a Latin American population assessing the profile of five adipokines.
GIANT CELL ARTERITIS (GCA): EXPERIENCE AT THE HOSPITAL CLÍNICO, UNIVERSIDAD DE CHILE
Pamela Wurmann Kiblisky1, Pedro Zamorano Soto2, Claudia Hernandez Spiess3, and Macarena Mac-Namara Hidalgo4. 1Hospital Clínico Universidad De Chile, Santiago, Chile, 2Hospital Clínico Universidad De Chile, santiago, Chile, 3Hospital Clínico Universidad De Chile, Santiago, Chile, 4Hospital Clínico Universidad De Chile, Santiago, Chile.
Introduction: GCA is the most frequent systemic vasculitis in patients over 50 years of age. The diagnosis is based on clinic, laboratory, images and histologic features. Temporal artery biopsy (TAB) may not be conclusive in up to 40% of patients. Ultrasound emerges as an alternative to TAB. There are few reports of GCA in Latin America and none in Chile.
Objective: To describe the characteristics of patients diagnosed with GCA between 2000 and 2019 in our center.
Material and Method: Demographic, clinical, laboratory, histopathology, imaging, treatment and follow-up variables were obtained from the medical records.
Results: 32 cases were included, average age at diagnosis was 70.5 years (range:57 -90), 81.3% were women The most common symptoms at disease onset were: Systemic (66%) follow by Musculoskeletal symptoms (56.3%). 10 patients (31%) had ophthalmologic symptoms. In 28.1% GCA was associated with polymyalgia, 71.8% had only cranial symptoms, 12.5% had cranial and extra cranial involvement and 12.5% had only extra cranial involvement. The median time between the onset of symptoms and diagnosis was 2 months (range: 0.5-8). 51.9% of patients presented anemia, 100% had elevated ESR and CRP (median 91 mm / hr., range 42-12 and 80 mg / dl range: 6.6-300 mg/dl, respectively). TAB was performed in 27 (84.4%) patients; 17 (65.4%) were positive. The most frequent histopathological finding was trans mural inflammation (42.3%) In 2 patients ultrasound was performed as a diagnostic method. All patients received induction therapy with corticosteroids (0.5 and 1 mg/kg/day). In 25 of 32 patients we obtained follow up information. 92% of the patients received some corticosteroid-sparing drug at some time during the evolution, methotrexate being the most frequently used (74%). 92% of the patients achieved clinical remission in the first year (28% during the first month, 40% between 1 and 2 months and 12% between 2 and 3 months of treatment). 58.5 % of the patients had a relapse during corticosteroid tapering. All relapses were minor.
Conclusion: This is the first series of GCA in Chilean patients. There was a small number or cases for nearly the 20 years included in the analysis. The clinical presentation was variable with a 25% of extra cranial involvement. The TAB had a good performance in our series being (+) in 72% of the cases. The most frequent histopathological finding was trans mural inflammation. The ultrasound as a diagnostic method is still under employed in our environment.
GUSELKUMAB, AN ANTI-INTERLEUKIN-23P19 MONOCLONAL ANTIBODY, IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: WEEK 24 RESULTS OF THE PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
Philip J. Mease1, Proton Rahman2, Alice Gottlieb3, Elizabeth Hsia4,5, Alexa P. Kollmeier4, Xie L. Xu4, Ramanand A. Subramanian4, Prasheen Agarwal4, Shihong Sheng4, Bei Zhou4, Désirée van der Heijde6, Federico Zazzetti7, and Iain B. McInnes8. 1Swedish Medical Center/Providence St Joseph Health and Univ Washington, Seattle, United States, 2Memorial Univ Newfoundland, St. Johns, Canada, 3Icahn School of Medicine at Mt Sinai, New York, United States, 4Janssen Research & Development, LLC, Spring House, United States, 5Univ Pennsylvania Medical Center, Philadelphia, United States, 6Leiden Univ Medical Center, Leiden, The Netherlands, 7Janssen LATAM Medical Affairs, Buenos Aires, Argentina, 8Univ Glasgow, Glasgow, United Kingdom.
Objectives: Guselkumab (GUS), an anti-interleukin-23p19 monoclonal antibody, is approved for psoriasis (PsO). We assessed GUS efficacy and safety in the DISCOVER-1 and DISCOVER-2 Phase 3 trials in psoriatic arthritis (PsA).
Methods: In DISCOVER-2, adults with active PsA despite non-biologic DMARDs and/or NSAIDs were randomized to GUS 100mg every 4 weeks (Q4W); GUS 100mg at W0, W4, Q8W (Q8W); or placebo (PBO). Concomitant stable DMARDs, oral corticosteroids, and NSAIDs were allowed. At W16, patients with <5% improvement in tender+swollen joints could initiate/increase the dose of permitted medications. Primary endpoint was W24 ACR20 response. Multiplicity-adjusted p-values for controlled endpoints, and nominal (unadjusted) p-values for uncontrolled endpoints, are presented. Adverse events (AEs) through W24 are reported.
Results: 739 treated patients in DISCOVER-2 with moderate-to-severe disease (mean swollen/tender joints:12/21, median CRP:1.2mg/dL, mean BSA with PsO:17.4%, IGA=3-4: 46.1% of patients) were analyzed. Significantly more GUS Q4W (63.7%) and Q8W (64.1%) vs PBO (32.9%) patients achieved W24 ACR20 response (both adjusted p<0.001). Both GUS doses separated from PBO by W4. Among patients with ≥3% BSA PsO&IGA ≥2 at W0, significantly more GUS Q4W (68.5%) and Q8W (70.5%) vs PBO (19.1%) patients achieved IGA response at W24 (both adjusted p<0.001). Significantly greater improvements from baseline were seen with GUS Q4W and Q8W vs PBO at W24 in HAQ-DI (–0.40, –0.37, –0.13, respectively; adjusted p<0.001) and SF-36 PCS (7.04, 7.39, 3.42, respectively; adjusted p≤0.011). Mean changes in W24 total modified vdH-S scores were significantly lower for GUS Q4W (0.29) and numerically lower for GUS Q8W (0.52) vs PBO (0.95; adjusted p=0.011 and p=0.072, respectively). Numerically larger mean improvements in SF-36 MCS scores were seen with GUS Q4W (4.22) and Q8W (4.17) than PBO (2.14; both adjusted p=0.072). Among pooled DISCOVER-1&2 patients with the condition at baseline, significantly higher proportions of patients had resolved enthesitis/dactylitis at W24 with GUS Q4W (44.9%/63.5%) and Q8W (49.6%/59.4%) vs PBO (29.4%/42.2%; all adjusted p<0.05). Numerically higher proportions of GUS Q4W and Q8W than PBO patients with W24 PASI75/90/100 (among patients with ≥3% BSA PsO&IGA ≥2 at W0) and MDA responses were observed. Serious AEs and serious infections occurred in 18/739 (2.4%) and 5/739 (0.7%) patients, respectively, and no patient died through W24.
Conclusions: In patients with active PsA, GUS significantly improved joint and skin symptoms, physical function, enthesitis and dactylitis and quality of life. GUS Q4W significantly reduced radiographic damage progression vs PBO. AEs were consistent with GUS safety in PsO patients.
IMPROVEMENTS IN HEALTH-RELATED QUALITY OF LIFE IN PSORIATIC ARTHRITIS PATIENTS TREATED WITH INTRAVENOUS GOLIMUMAB, AN ANTI-TNFα MONOCLONAL ANTIBODY: 1-YEAR RESULTS OF A PHASE III TRIAL
Elaine M. Husni1, Diane Harrison2, Elizabeth Hsia3, Eric K. H. Chan2, Chenglong Han2, Shelly Kafka4, Kim Hung Lo2, Lilianne Kim2, Federico Zazzetti5, and Arthur Kavanaugh6. 1Department of Rheumatologic and Immunologic Diseases, Cleveland Clinic, Cleveland, United States, 2Janssen Research & Development, LLC, Spring House, United States, 3Janssen Research & Development, LLC/University of Pennsylvania, Spring House/Philadelphia, United States, 4Janssen Scientific Affairs, LLC, Horsham, United States, 5Janssen LATAM Medical Affairs, Buenos Aires, Argentina, 6University of California, San Diego School of Medicine, La Jolla, United States.
Objectives: In the randomized, phase 3, GO-VIBRANT study, more patients with psoriatic arthritis (PsA) achieved ACR 20/50/70 at 24 weeks in the anti-TNFα monoclonal antibody golimumab IV (GLM-IV) group than placebo (PBO) (p<0.001). After cross-over from PBO to GLM-IV at Week 24, 52-week achievement of ACR responses was similar between the two treatment groups.1 Here we examine effects on measures of health-related quality of life (HRQoL) for up to 52 weeks of treatment.
Methods: Adult patients with active PsA who met CASPAR criteria (N=480) were randomized (1:1) to GLM-IV 2 mg/kg at Weeks 0, 4, then every 8 weeks or matching PBO through Week 20 then cross-over to GLM-IV at Weeks 24, 28, then every 8 weeks. Physical function was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Measures of HRQoL included Short-Form-36 Physical and Mental Component Summaries (SF-36 PCS/MCS), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, EuroQol-5D visual analog scale (EQ-VAS), and Dermatology Life Quality Index (DLQI), which were assessed at Weeks 0, 8, 14, 24, 36, and 52.
Results: GLM- IV and PBO groups had comparable HRQoL characteristics at baseline. At Week 24, changes from baseline were greater for GLM-IV vs PBO (HAQ-DI, -0.63 vs -0.14; SF-36 PCS, 9.4 vs 2.4; SF-36 MCS, 5.3 vs 0.8; FACIT-Fatigue, 9.2 vs 2.3; EQ-VAS, 20.2 vs 5.5; and DLQI, -8.1 vs -1.9, respectively). At Week 24, more patients receiving GLM-IV than PBO achieved minimal clinically important improvements from baseline in HAQ (≥0.35 points),2 SF-36 (≥5 points),3 and FACIT-fatigue (≥4 points).4 Among patients randomized to GLM-IV, changes in HRQoL measures were maintained from Week 24 to Week 52. Among patients randomized to PBO, after switching to GLM-IV at Week 24, improvements in HRQoL measures from Week 36 to Week 52 were comparable to those of patients originally randomized to GLM-IV.
Conclusions: Improvements in HRQoL among patients with PsA after 24 weeks’ GLM-IV treatment were greater than PBO and were maintained through Week 52 of treatment. Patients switching from PBO to GLM-IV at Week 24 experienced improvements in HRQoL by Week 36, which were maintained through Week 52 and were similar to those achieved by patients originally randomized to GLM-IV.
1. Husni et al. Arthritis Care Res. 2019 DOI:10.1002/acr.23905.
2. Mease et al. J Rheumatol. 2011; 38: 2461.et al.
3. Lubeck et al. 2004; 22: 27.
4. Cella et al. J Rheumatol. 2005; 32:811.
BASELINE CYTOTOXIC GENE EXPRESSION ASSOCIATES WITH USTEKINUMAB RESPONSE IN SYSTEMIC LUPUS ERYTHEMATOSUS
Loqmane Seridi1, Matteo Cesaroni1, Matthew Loza1, Jessica Schreiter1, Kristen Sweet1, Yevgeniya Orlovsky1, Isabelle Baribaud1, Ashley Orillion1, Peter Lipsky2, Ronald van Vollenhoven3, Bevra Hahn4, George Tsokos5, Marc Chevrier1, Shawn Rose1, Frédéric Baribaud1, Federico Zazzetti6, and Jarrat Jordan1. 1Janssen Research & Development, LLC, Spring House, United States, 2AMPEL BioSolutions, LLC, Charlottesville, United States, 3Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands, 4University of California, Los Angeles, United States, 5Beth Israel Deaconess Medical Center, Harvard Medical, Boston, United States, 6Janssen LATAM Medical Affairs, Buenos Aires, Argentina.
Objectives: Systemic Lupus Erythematous (SLE) is a diverse disease. In a phase 2 trial of mild-to-moderate SLE patients, ustekinumab (UST) improved disease activity compared with placebo (PBO). We previously reported an association of IFN-γ reduction with response to UST, suggesting an impact on the IL12/Th1 axis. We performed unbiased transcriptomic analysis from baseline whole blood to identify genes that discriminate UST responders (UST-R) from non-responders (UST-NR) using SLE Responder Index (SRI)-4 at Week 24 to define response.
Methods: UST was studied in a phase 2 study of 102 patients with seropositive SLE and active disease despite standard therapy. Patients were randomized 3:2 to receive IV UST 6 mg/kg or PBO followed by subcutaneous injections of UST 90mg or PBO every 8 weeks. Whole blood gene expression at baseline was measured via microarray using RNA samples from 100 patients. An unbiased approach was used to identify gene signatures associated with UST response. Recombinant IL-12 or IL-23 was incubated in vitro with whole blood from 6 healthy donors for 24h and RNA-Seq was performed to determine the effect of these treatments on genes comprising the UST response signature.
Results: A non-biased machine learning algorithm identified a 9-gene whole blood signature composed primarily of cytotoxic cell-associated transcripts (PRF1, KLRD1, GZMH, NKG7, GNLY, FGFBP2, TRGC2, TARP, TRGV2) that was enriched at baseline in UST-R vs UST-NR. By Gene Set Variation Analysis, the cytotoxic signature enrichment in UST-NR was less at baseline than both UST-R and healthy controls (p=0.0087, p=0.056, respectively), whereas UST-R cytotoxic gene enrichment was similar to healthy controls (p=0.31). No significant difference in cytotoxic signature enrichment was observed at baseline between PBO responders and PBO non-responders or healthy controls. Enrichment levels of the cytotoxic gene signature remained stable over time in PBO and UST-NR groups while a trend of decreased cytotoxic signature was observed in UST-R, although never reaching levels seen in UST-NR. The targets of UST, and the cytotoxic signature, whole blood was stimulated with these cytokines in vitro. Recombinant IL-12, but not IL-23, resulted in increased expression of representative members of this cytotoxic gene signature.
Conclusions: We identified a novel cytotoxic signature in blood that associated with UST response in SLE. The observation that IL-12 can increase this signature in vitro and is a robust inducer of cytotoxic cell activity as well as IFN-γ suggests an important role of IL-12 blockade in the mechanism of action of UST in SLE.
BURDEN OF SYSTEMIC LUPUS ERYTHEMATOSUS IN LATIN-AMERICA: A LITERATURE REVIEW
Federico Zazzetti1, Diana González-Bravo2, Gerardo Machnicki3, Atanacio Valencia4, Jorge Alvarez albarran2, Edgar Guerrero2, and Hudson Santos2. 1Janssen LATAM Medical Affairs, Buenos Aires, Argentina, 2Janssen Regional HEOR Center of Excellence, LATAM, 3Janssen Real World Evidence Director, LATAM, 4Janssen Regional Market Access Director, LATAM.
Objectives: Different cohorts like GLADEL (Grupo LAtinoamericano De Estudio del Lupus) and LUMINA (LUpus in MInority Populations: NAture vs. Nurture) have reported that African Latin-American (ALA) and mestizo patients have more active and severe disease with higher frequency of renal involvement. This could lead to a considerable burden for patients and health care systems. Objective: Identify the clinical burden of Systemic Lupus Erythematosus (SLE) for Latin-American (LATAM) patients.
Methodology: A literature review of publications available for SLE in LATAM was performed, considering systematic literature reviews, metanalyses, observational studies, real world evidence (RWE) in English, Portuguese and Spanish. EMBASE, MEDLINE, LILACS, Value in health, ACR, EULAR, PANLAR, LACA and International Congress on SLE, were the source of the evidence. Timeframe considered was the last 5 years for all epidemiological designs, except for cohorts in which the complete description was included throughout time. A qualitative and narrative evidence synthesis was done for GLADEL publications, Epidemiology, Health Resource Utilization (HRU), RWE, quality of life (QoL) and Lupus Nephritis (LN).
Results: Overall, 2067 titles were retrieved, 413 in LILACS, 216 in MEDLINE, 100 in EMBASE and 1295 remaining unpublished. After filtering for title and content, the synthesis was based on 217 publications. GLADEL cohort included 20 manuscripts and 19 conference abstracts, including the first LATAM treatment guideline for SLE. Four epidemiological studies were published, and 4 conference abstracts found from Ecuador, Argentina, Paraguay and Colombia, mostly focused on gender, risk factors and clinical/immunological characteristics. Only 1 publication was found for HRU. Eleven published RWE studies and 7 conference abstracts helped characterize the treatment pathways for SLE in LATAM, considering severity, complications, organ damage and flares. Five manuscripts and 4 abstracts assessed QoL, including mortality and absenteeism. LN and its main risk factors, renal transplantation outcomes, prognosis and survival rates were identified in 5 manuscripts and 4 abstracts.
Conclusions: Overall, the largest number of publications were found in regional journals, however, over 50% of them are only indexed in local databases or not being published at all, highlighting the opportunity the region has to increase publications in peer-reviewed journals and worldwide-indexed databases. Moreover, there is a lack of data regarding the economic burden of SLE in LATAM. Finally, GLADEL has set the example for other cohorts, expanding the knowledge of SLE in LATAM patients. LATAM SLE patients usually have a severe clinical presentation, high rate of organ damage and renal involvement, requiring more healthcare resources.
GUSELKUMAB, AN ANTI-INTERLEUKIN-23P19-SUBUNIT MONOCLONAL ANTIBODY, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS WHO WERE BIOLOGIC-NAÏVE OR PRIOR TNFα INHIBITOR-TREATED: WEEK 24 RESULTS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
Atul Deodhar1, Philip Helliwell2, Wolf-Henning Boencke3, Elizabeth C. Hsia4,5, Alexa P. Kollmeier4, Ramanand A. Subramanian4, Xie L. Xu4, Shihong Sheng4, Bei Zhou4, Federico Zazzetti6, and Christopher Ritchlin7. 1Oregon Health & Science Univ, Portland, United States, 2Univ Leeds, Leeds, United Kingdom, 3Geneva Univ Hospitals, Geneva, Switzerland, 4Janssen Research & Development, LLC, Spring House, PA/San Diego, CA, United States, 5Univ Pennsylvania Medical Center, Philadelphia, United States, 6Janssen LATAM Medical Affairs, Buenos Aires, Argentina, 7Univ Rochester Medical Center, Rochester, United States.
Objectives: Guselkumab (GUS), an anti-interleukin-23p19-subunit monoclonal antibody, is approved to treat psoriasis (PsO). We evaluated GUS efficacy and safety in a Phase 3, double-blind, placebo (PBO)-controlled trial in patients with active psoriatic arthritis (PsA) who were biologic-naïve or prior TNFα inhibitor (TNFi)-treated (DISCOVER-1).
Methods: Adults with active PsA despite standard therapies were randomized 1:1:1, stratified by Week (W), DMARD use and prior TNFi use, to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W (Q8W); or PBO. Approximately 30% of patients could have received or have had inadequate response to 1-2 TNFi. Concomitant stable use of DMARDs, oral corticosteroids, and NSAIDs was allowed. At W16, patients with <5% improvement in both tender and swollen joint counts could start or increase the dose of permitted medications while continuing study treatment. The primary endpoint was W24 ACR20. Global and US multiplicity control procedures were prespecified and US procedure results are presented. Unadjusted (nominal) p-values are provided for other endpoints. Adverse events (AEs) through W24 are reported.
Results: 381 patients were treated and analyzed; baseline characteristics were consistent with moderate-to-severe disease (mean BSA involved with PsO:13.4%, patients with IGA=3-4:42.5%; mean swollen/tender joint counts:9.8/19.3). Significantly more patients receiving GUS Q4W (59.4%) and Q8W (52.0%) vs PBO (22.2%, both p<0.001) achieved W24 ACR20 response. Consistent response rates were observed in subgroups of patients with or without prior TNFi use. Significantly greater improvements were seen with GUS Q4W and Q8W vs PBO in W24 HAQ-DI (–0.40, –0.32, –0.07, respectively, both p<0.001) and SF-36 PCS scores (6.87, 6.10, 1.96, respectively, both p<0.001). Among 249 patients with ≥3% BSA PsO&IGA ≥2 at W0, significantly more patients achieved IGA response with GUS Q4W (75.3%) and Q8W (57.3%) vs PBO (15.4%, both p<0.001). Higher proportions of patients achieved W16 ACR20 response, W16/24 ACR50 response, W24 ACR70 response, and W24 PASI75/90/100 responses. More patients achieved W24 MDA response with GUS Q4W (30.5%) and Q8W (22.8%) vs PBO (11.1%, both p<0.01). Serious AEs, serious infections, and death occurred in 9/381, 2/381, and 1/381 patients, respectively.
Conclusions: In patients with active PsA who were biologic-naïve or had been treated with TNFi, both GUS Q4W and Q8W demonstrated efficacy for joint and skin symptoms, physical function, and quality of life relative to PBO. Observed AEs were consistent with GUS safety established in PsO.
EFFECTS OF INTRAVENOUS GOLIMUMAB, AN ANTI-TNFα MONOCLONAL ANTIBODY, ON HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH ANKYLOSING SPONDYLITIS: 1-YEAR RESULTS OF A PHASE III TRIAL
John Reveille1, Atul Deodhar2, Diane Harrison3, Elizabeth Hsia4, Eric K. H. Chan3, Shelly Kafka5, Kim Hung Lo3, Lilianne Kim3, Federico Zazzetti6, and Chenglong Han3. 1University of Texas McGovern Medical School, Houston, United States, 2Oregon Health & Science University, Portland, United States, 3Janssen Research & Development, LLC, Spring House, United States, 4Janssen Research & Development, LLC/University of Pennsylvania, Spring House/Philadelphia, United States, 5Janssen Scientific Affairs, LLC, Horsham, United States, 6Janssen LATAM Medical Affairs, Buenos Aires, Argentina.
Objectives: In patients with ankylosing spondylitis (AS), IV administration of the anti-TNFα antibody golimumab (GLM-IV) resulted in improvements in composite measures of various aspects of the disease (eg, ASAS percent response, BASDAI, and BASFI) that were greater than placebo (PBO) at Week 16 or earlier in the GO-ALIVE study.1 The improvements were maintained for up to 1 year of treatment.2 Here we examine treatment effects on health-related quality of life (HRQoL).
Methods: Adult patients with definite AS (per modified NY criteria), BASDAI ≥4, total back pain VAS ≥4, CRP ≥0.3 mg/dL, and inadequate response to NSAIDs were randomized to GLM-IV 2 mg/kg at Weeks 0 and 4 then every 8 weeks, or to PBO at Weeks 0, 4, and 12 and GLM-IV at Weeks 16 and 20, then every 8 weeks. Stable doses of methotrexate (≤25 mg/week), sulfasalazine, hydroxychloroquine, NSAIDs, other analgesics, and low dose oral corticosteroids were permitted for patients who were receiving these medications at baseline. Measures of HRQoL included the Ankylosing Spondylitis Quality of Life questionnaire (ASQoL), Short Form-36 physical and mental component summary scores (SF-36 PCS/MCS), Medical Outcomes Study Sleep Scale (MOS-SS), and EuroQoL visual analog scale (EQ VAS), each measured at Weeks 16, 28, and 52. p values provided are nominal, not adjusted for multiplicity.
Results: At Week 16, patients with AS receiving GLM-IV had greater improvements from baseline in HRQoL than those receiving PBO in each measure (ASQoL, -5.4 vs -1.8; SF-36 PCS, 8.5 vs 2.9; SF-36 MCS, 6.5 vs 0.78; MOS-SS, 6.6 vs 2.5; and EQ VAS, 20.3 vs 4.8, respectively; all p< 0.001). Changes from baseline were maintained through Week 52 in patients randomized to GLM-IV. Patients switched from PBO to GLM-IV at Week 16 demonstrated improvement from baseline by Week 28, which was maintained through Week 52 and was similar to that of patients who received GLM-IV at baseline.
Conclusions: Improvements in HRQoL among patients with active AS treated with GLM-IV were greater than PBO at Week 16 and were maintained through Week 52. Patients switching from PBO to GLM-IV at Week 16 experienced improvements in HRQoL by Week 28 and maintained the improvement through Week 52 at levels similar to those of the patients originally randomized to GLM-IV.
1. Deodhar et al. J Rheum. 2018; 45:341:2. Reveille et al. J Rheum. 2019. DOI: 10.3899/jrheum.180718.
USTEKINUMAB AND GUSELKUMAB TREATMENT RESULTS IN DIFFERENCES IN SERUM IL-17A, IL-17F AND CRP LEVELS IN PSORIATIC ARTHRITIS PATIENTS: A COMPARISON FROM USTEKINUMAB PHASE 3 AND GUSELKUMAB PHASE 2 PROGRAMS
Stefan Siebert1, Matthew J. Loza2, Qingxuan Song2, Iain B. McInnes1, Federico Zazzetti3, and Kristen Sweet2. 1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom, 2Janssen Research and Development, LLC, Spring House, United States, 3Janssen LATAM Medical Affairs, Buenos Aires, Argentina.
Objectives: Ustekinumab (UST) is a monoclonal antibody (mAb) that binds the p40 epitope which is shared by IL-12 and IL-23, whereas guselkumab (GUS) is a mAb that selectively binds the p19 subunit of IL-23. In recent studies, both UST (Phase 3 programs) and GUS (Phase 2 program) have demonstrated a reduction in musculoskeletal clinical signs and symptoms and improvement of psoriatic lesions in patients with active psoriatic arthritis (PsA), implicating the IL-12/23 pathway in disease pathogenesis. The objective of this study was to explore the post-treatment pharmacodynamic changes of IL-17A, IL-17F, and CRP with GUS and UST in the context of PsA.
Methods: Serum protein levels of IL-17A, IL-17F, and CRP were measured in 142 subjects and 38 matched healthy controls from the GUS Phase 2 study at Weeks 0, 4, and 16. In the UST Phase 3 studies, biomarkers were assayed at Weeks 0, 4, and 24 as follows: IL-17A (n=474), IL-17F (n=237), CRP (n=927).
Results: At baseline, the Th17 effector cytokines IL-17A and IL-17F were elevated in the serum of PsA subjects in the GUS Phase 2 cohort compared to healthy controls. IL-17A and IL-17F levels significantly correlated with affected skin body surface area, but not swollen or tender joint scores, in both studies. While none of the baseline levels of evaluated cytokines were associated with American College of Rheumatology (ACR) or Psoriasis Area Severity Index (PASI) clinical responses to UST, baseline IL-17F levels were modestly associated with ACR20 response to GUS at Week 24. Both UST and GUS treatment resulted in pharmacodynamic decreases in IL-17A, IL-17F, and CRP levels, with GUS treatment restoring IL-17A and IL-17F levels to that of healthy controls by Week 16. Consistent with being a component of ACR scores, CRP changes were significantly associated with ACR20 responses to both UST and GUS treatment. Weeks 4 and 16 changes in IL-17F with GUS treatment were significantly associated with ACR20 response at Week 24. Week 24 PASI75 response to GUS was significantly associated with Week 4 changes in IL-17A, with a similar trend observed at Week 16.
Conclusions: These results underscore the relevance of the IL-23/Th17 pathway in PsA, with GUS treatment providing a stronger suppression of the pathway than UST treatment. The significant associations of changes in IL-17A and IL-17F levels with GUS treatment with PASI75 and ACR20 response, respectively, support the importance of the IL-23/Th17 pathway for both skin and joint pathologies.
MAPPING REAL-WORLD PSORIATIC ARTHRITIS PATIENTS TO CLINICAL TRIAL ELIGIBILITY CRITERIA
Regan Arendse1, Derek Haaland2, Isabelle Fortin3, Proton Rahman4, Emmanouil Rampakakis5, Odalis Asin-Milan6, Meagan Rachich6, Francois Nantel6, and Allen J. Lehman6. 1University of Saskatchewan, Saskatoon, Canada, 2McMaster University, Hamilton, Canada, 3Centre de Rhumatologie de I’Est du Québec á Rimouski, Rimouski, Canada, 4Memorial University of Newfoundland, St. John’s, Canada, 5JJS Medical Research, Montreal, Canada, 6Janssen Inc., Toronto, Canada.
Objectives: Results of real-world studies may be extrapolated to overall patient populations, whereas clinical trials present outcomes which can be limited in generalizability due to stringent eligibility criteria. This analysis sought to assess the proportion of psoriatic arthritis (PsA) patients treated with golimumab in Canadian routine care qualifying for a pivotal randomized controlled trial (RCT) and explore potential differences in outcomes.
Methods: This is a post-hoc analysis of data from the BioTRAC registry. PsA patients initiating treatment with subcutaneous golimumab, including both biologic-treatment naïve and experienced (<6 months) individuals, were categorized as “Eligible” or “Non-eligible” based on inclusion/exclusion criteria of the GO-REVEAL RCT. Reasons for non-eligibility and between-group differences in baseline characteristics were assessed with univariate statistics. Impact of eligibility on achieving the following clinical outcomes at 6/12 months was assessed using logistic regression adjusting for respective baseline level/status: Minimal Disease Activity (MDA;5/7 MDA criteria), Very Low Disease Activity (VLDA;7/7 MDA criteria), PASI75, HAQ <0.5, and absence of enthesitis and dactylitis. Treatment retention was evaluated using Cox regression adjusting for disease duration and eligibility. Safety was evaluated through incidence of adverse events (AEs).
Results: 171 patients were included: 48 (28.1%) were considered Eligible and 123 (71.9%) were considered Non-eligible for GO-REVEAL. Main reasons for ineligibility were unconfirmed active PsA at baseline (≥2 TJC28 and SJC28, BSA >0: n=103/123; 83.7%) and previous biologic use (n=40/123; 32.5%). Mean [SD] baseline disease parameters were significantly (p<0.05) higher in Eligible vs. Non-Eligible patients for MDGA 0-10 (6.6 [1.9] vs. 5.2 [2.0]), PtGA 0-100 (32.3 [31.6] vs. 15.3 [20.8]), TJC28 (12.0 [6.5] vs. 7.0 [6.6]), SJC28 (9.1 [4.5] vs. 4.0[4.4]), enthesitis (3.3 [4.4] vs. 1.8 [2.8] affected joints), PASI (4.7 [6.8] vs. 1.8 [2.4]) and HAQ (1.4 [0.6] vs. 1.0 [0.7]).
Non-eligible patients were significantly less likely to achieve PASI75 at months 6 and 12 (OR [95%CI]: 0.27 [0.11 -0.64], 0.25 [0.09 – 0.64], respectively] and HAQ <0.5 at month 6 (0.29 [0.10-0.84]) and remain on treatment (HR [95%CI] for discontinuation: 2.4 [1.4-4.2]). The incidence of AEs was comparable between groups (Eligible vs. Non-eligible: 64.6% vs. 68.3%) without remarkable differences in the safety profile.
Conclusions: The majority of PsA patients treated with golimumab in routine care would not have been eligible for GO-REVEAL. Non-eligibility was driven primarily by an absence of active PsA confirmation, resulting in higher baseline disease activity in Eligible patients. Eligibility to GO-REVEAL was a significant positive predictor of PASI and HAQ improvement.
INFECTIONS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH GOLIMUMAB
Louis Bessette1, Proton Rahman2, John Kelsall3, Jane Purvis4, Emmanouil Rampakakis5, Allen J. Lehman6, Meagan Rachich6, Francois Nantel6, Odalis Asin-Milan6. 1Université Laval, Quebec, Canada, 2Memorial University of Newfoundland, St. John’s, Canada, 3University of British Columbia, Vancouver, Canada, 4Ontario Rheumatology Association, Peterborough, Canada, 5JJS Medical Research, Montreal, Canada, 6Janssen Inc., Toronto, Canada..
Objectives: Biologic use in rheumatoid arthritis (RA) is a well-characterized risk factors for infections. The aim of this analysis was to characterize the incidence of infection in RA patients treated with golimumab in Canadian routine care, as well as assess the impact of oral corticosteroid (CS) and DMARD use on infection.
Methods: This is a post-hoc analysis of the BioTRAC registry. Patients with RA who initiated treatment with subcutaneous golimumab were included in this analysis. The incidence density rates (IDR) of total, serious (SI), and non-serious (NSI) infections were calculated for the overall follow-up period as well as by 6-month interval. Negative binomial and cox regressions were used to assess the impact of CS and DMARD use, as well as CS and methotrexate (MTX) dose levels. Time to first infection and time to treatment discontinuation were assessed with the Kaplan-Meier estimator of the survival function, and the impact of concomitant CS and DMARD use was assessed with the log rank test.
Results: 530 patients were included with a mean (SD) age of 57.7 (13.0) years and disease duration of 8.0 (8.3) years. Of these, 74 (14.0%) were treated with ≤15 mg/week MTX, 280 (52.8%) with >15 mg/week MTX, while 173 (32.6%) were not on MTX. In terms of CS, 72 (13.6%) were treated with ≤5 mg/day, 63 (11.9%) with >5 mg/day, and 391 (73.8%) were not on CS.
Over a mean follow-up duration of 27.0 months, the IDR for total infections, NSI, and SI was 35.10 events/100 PYs, 32.90 events/100 PYs, and 2.23 events/100 PYs. Median estimated time to first infection was 52.9 months (SI: 84.9 months; NSI: 55.1 months). The incidence of total infections was 44.0, 37.3, 35.1, 29.4, 31.1, 35.7, 19.3, 7.4 and 0.0 events/100 PYs at 0-6 months, 6-12 months, 12-24 months, 24-36 months, 36-48 months, 48-60 months, 60-72 months, 72-84 months and 84-90 months, respectively. Longer follow-up duration was significantly associated with higher number of NSI (HR [95%CI]: 1.011 [1.006-1.017]) but not SI (1.011 [0.988-1.035]), while neither the use of DMARD, CS nor MTX was found to have an impact.
Conclusions: Higher IDR was observed during the first 6 months of treatment and decreasing thereafter. CS and DMARD treatment did not impact retention of golimumab treatment. These results support the notion that CS should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered.
MAPPING REAL-WORLD RHEUMATOID ARTHRITIS PATIENTS TO CLINICAL TRIAL ELIGIBILITY CRITERIA
Edward Keystone1, Wojciech Olszynski2, Louis Bessette3, Proton Rahman4, Emmanouil Rampakakis5, Allen J. Lehman6, Odalis Asin-Milan6, Francois Nantel6, and Meagan Rachich6. 1University of Toronto, Toronto, Canada, 2University of Saskatchewan, Saskatoon, Canada, 3Université Laval, Quebec, Canada, 4Memorial University of Newfoundland, St. John’s, Canada, 5JJS Medical Research, Montreal, Canada, 6Janssen Inc., Toronto, Canada.
Objectives: Results of real-world studies may be extrapolated to overall patient populations, whereas clinical trials outcomes can be limited in generalizability due to stringent eligibility criteria. This analysis sought to assess the proportion of rheumatoid arthritis (RA) patients treated with golimumab in Canadian routine care qualifying for a pivotal randomized controlled trial (RCT) and explore potential differences in outcomes.
Methods: This is a post-hoc analysis of data from the Biologic Treatment Registry Across Canada (BioTRAC). Patients with RA initiating treatment with subcutaneous golimumab were categorized as “Eligible” or “Non-eligible” based on inclusion/exclusion criteria of the GO-FORWARD RCT. Reasons for non-eligibility and between-group differences in baseline characteristics were assessed with univariate statistics. Treatment retention was compared using the log rank test. Safety was evaluated through incidence of adverse events (AEs).
Results: 410 patients were included: 31 (7.6%) were considered Eligible and 379 (92.4%) were considered Non-Eligible for GO-FORWARD. Among Non-Eligible patients, baseline inclusion criteria violated were: methotrexate dose outside >= 15 - <=25 mg/week (n = 163/379; 43.0%); patients not meeting 2/3 of 1) CRP ≥1.5 mg/dL or ESR ≥ 28 mm/h, 2) ≥30 minutes of morning stiffness, 3) Anti-CCP or RF positive (n=160/379; 42.2%); and non-active RA (<3 SJC and <2 TJC: n = 93/379; 24.5%). The primary exclusionary factor was baseline DMARD(s) use other than methotrexate (n = 243/379; 64.1%).
Mean age, disease duration and gender were comparable (p>0.05) across eligibility status. Significantly greater baseline disease activity was observed in Eligible vs. Non-Eligible patients for mean [SD] DAS28-ESR (5.7 [1.2] vs. 5.1 [1.4]) and DAS28-CRP (5.4 [0.9] vs. 4.8 [1.3]); TJC (11.8 [6.7] vs. 9.4 [6.9]) and SDAI (37.0 [13.7] vs. 30.9 [15.3]) were higher for Eligible patients, and approached significance (p<0.065). Median [SE] treatment retention, although longer in Eligible patients, was not significantly different (Eligible vs. Non-Eligible: 4.0 [1.2] vs. 2.7 [0.2]) years; p=0.243). ≥1 AE was reported for 67.7% (n= 21/31) of Eligible and 69.1% (n=262/379) of Non-Eligible patients with lower incidence of serious infections in the latter.
Conclusions: The vast majority of RA patients treated with golimumab in Canadian routine care would not have been eligible for GO-FORWARD. Non-eligibility was driven primarily by deviations in baseline methotrexate use and/or dose. Requirements concerning laboratory parameters and minimum joint involvement resulted in an Eligible population with higher baseline disease activity. No differences were observed between patient subgroups in terms of real-word treatment retention or safety.
MAPPING REAL-WORLD ANKYLOSING SPONDYLITIS PATIENTS TO CLINICAL TRIAL ELIGIBILITY CRITERIA
Dalton Sholter1, Robert Inman2, Ariel Masetto3, Proton Rahman4, Emmanouil Rampakakis5, Odalis Asin-Milan6, Meagan Rachich6, Francois Nantel6, and Allen J. Lehman6. 1University of Alberta, Edmonton, Canada, 2University Health Network, Toronto, Canada, 3Université de Sherbrooke, Sherbrooke, Canada, 4Memorial University of Newfoundland, St. John’s, Canada, 5JJS Medical Research, Montreal, Canada, 6Janssen Inc., Toronto, Canada.
Objectives: Results of real-world studies may be extrapolated to overall patient populations, whereas clinical trials outcomes can be limited in generalizability due to stringent eligibility criteria. This analysis sought to assess the proportion of ankylosis spondylitis (AS) patients treated with golimumab in Canadian routine care qualifying for the pivotal randomized controlled trial (RCT), and to explore potential differences in outcomes.
Methods: This is a post-hoc analysis of data from the BioTRAC registry. Patients with AS who initiated treatment subcutaneous golimumab were categorized as “Eligible” or “Non-eligible” based on the inclusion/exclusion criteria of the GO-RAISE RCT. Reasons for non-eligibility, as well as between-group differences in baseline characteristics, were assessed with univariate statistics. Impact of eligibility on achievement of the following clinical outcomes at 6/12 months was assessed using logistic regression adjusting for respective baseline clinical activity. Treatment retention was compared using the log rank test. Safety was evaluated through incidence of adverse events (AEs).
Results: 357 patients were included: 184 (51.5%) were considered Eligible and 173 (48.5%) were considered Non-Eligible for GO-RAISE. Primary exclusionary reasons were baseline BASDAI and spinal pain scores <4 (n= 59/173 [34.1%] and 42/173 [24.3%], respectively), no prior DMARD/NSAID use (55/173; 31.8%), and previous biologic use (n=62/173; 35.8%).
Significantly greater (p<0.05) baseline functional impairment and disease activity was observed in Eligible vs. Non-Eligible patients for mean [SD] HAQ-DI (1.2 [0.6] vs. 0.9 [0.6]), BASFI (6.8 [1.5] vs. 5.3 [2.4]), BASDAI (5.8 [2.2] vs. 4.8 [2.7]), and ASDAS (3.6 [0.8] vs. 3.2 [1.1]). No impact of eligibility on outcomes was observed, except Month 12 achievement of HAQ <0.5 which was 55% less likely in Non-eligible patients (OR [95%CI]: 0.45 [0.23-0.93]; p=0.03). Treatment retention, although lower for Eligible vs. Non-Eligible patients (Median [SE]: 1.6 [0.3] vs. 2.3 [0.3] years), was statistically comparable (p=0.167). ≥1 AE was reported by 74.5% (n=137/184) of Eligible and 71.1% (n=123/173) of Non-Eligible patients.
Conclusions: Almost half of AS patients treated with golimumab in routine care would not have been eligible for GO-RAISE. Non-eligibility was driven primarily by deviations in prior medication use and disease activity thresholds. Real-world effectiveness, retention and safety were comparable. BASDAI >4 may be too restrictive since this study indicates comparable response rates and retention even with baseline BASDAI <4. Real world patients reflect a broader spectrum of AS than that seen in RCTs (shorter disease duration, lower BASDAI and BASFI) yet show comparable response rates.
APPLICATION OF TREAT TO TARGET AND IMPACT OF SUSTAINED LOW DISEASE ACTIVITY OR REMISSION ON FUNCTION IN RHEUMATOID ARTHRITIS PATIENTS
Louis Bessette1, Edward Keystone2, Proton Rahman3, Keltie Anderson4, Emmanouil Rampakakis5, Allen J. Lehman6, Meagan Rachich6, Francois Nantel6, Odalis Asin-Milan6. 1Université Laval, Quebec, Canada, 2University of Toronto, Toronto, Canada, 3Memorial University of Newfoundland, St. John’s, Canada, 4University of Saskatchewan, Saskatoon, Canada, 5JJS Medical Research, Montreal, Canada, 6Janssen Inc., Toronto, Canada.
Objectives: The aim of this analysis was to compare between enrolment periods rheumatoid arthritis (RA) treatment outcomes and frequency of treating to target, and to assess the impact of target type on long-term function.
Methods: This is a post-hoc analysis of data from the BioTRAC registry. Patients with RA who initiated treatment with infliximab or subcutaneous golimumab were included. Patients were grouped into enrolment periods: 2002-2004, 2005-2008, 2009-2012, 2013-2015, 2016-2017. Achievement of LDA (CDAI LDA or SDAI LDA or SJC≤1), remission (CDAI remission or SDAI remission or SJC=0), and sustained LDA or remission (at 6 and 12 months) were compared between enrolment periods with the Chi-square test and multivariate logistic regression. The impact of achieving LDA or remission at 6 months, 12 months, or both (sustained) on HAQ-DI at 18 months was assessed with one-way ANOVA and generalized linear models.
Results: 1420 patients treated with anti-TNFs (IFX: n=890; GLM: n=530) were included. Over calendar time, a significant decrease in baseline disease duration and disease activity scores (CDAI, SDAI, SJC28, TJC28, HAQ) was observed (p<0.001).
Across enrolment periods, significant differences were observed in target achievement with higher rates observed in more recent years. Upon adjusting for baseline CDAI and prior biologic exposure, no differences between enrolment periods were observed in achieving LDA, remission or sustained LDA/remission at 6 months; however, significantly (p=0.030) higher odds of achieving remission at 12 months were observed in more recent years.
Among patients not achieving LDA at 6 and 12 months, an intervention was applied in approximately 40% of patients, without significant differences between enrolment periods. Between 6 and 12 months, the most common intervention was anti-TNF discontinuation (64.9% of non-LDA achievers), followed by DMARD addition (9.8%), NSAID addition (8.8%), or steroid addition (7.2%). Similar results were obtained post 12 months.
Patients achieving sustained LDA, followed by those achieving LDA either at 6 or 12 months had significantly lower HAQ-DI at 18 months compared to patients not achieving LDA at either timepoint (0.8 vs. 1.1 vs. 1.4; p<0.001). Similar results were observed when evaluating achievement of disease remission albeit with greater impact on HAQ-DI at 18 months (0.7 vs. 1.1 vs. 1.2; p<0.001). Adjustment for baseline HAQ-DI did not impact the results.
Conclusions: Target achievement has increased over time although emphasis in treating to target may be placed in the first 6 months of treatment. Achieving stricter targets was associated with better long-term patient function.
CLINICAL CHARACTERISTICS AND BIOLOGICAL TREATMENT IN 66 PATIENTS WITH RHEUMATOID ARTHRITIS: AN OBSERVATIONAL STUDY IN THE SOUTHERNMOST PART OF CHILE
Zosimo Maravi Torrealva1, Bellanides Mansilla Aravena1, Paula Burgos Cañete2, Mariana Palacios Bautista1, Natalia Montaña Alvarado3, Andrea Montiel Varas3, Fernanda Neira Castillo3, and Camila Ojeda Galindo3. 1Unidad de Reumatología Hospital Clínico Magallanes, Punta Arenas, Chile, 2Unidad de Inmunología Clínica y Reumatología, Pontificia Universidad Católica de Chile, Santiago, Chile, 3Facultad de Medicina Universidad de Magallanes, Punta Arenas, Chile.
Introduction: Rheumatoid arthritis (RA) is the most frequent inflammatory arthritis; in Chile it has a prevalence of 0.6%. Since 2015, the Chilean health system gives universal access to biologic disease-modifying antirheumatic drugs (bDMARD). The Clinical Hospital of Magallanes (CHM) is the regional center of reference for treatment and follow up of these patients.
Objectives: To describe the most relevant clinical manifestations and treatments received by patients with RA diagnosis.
Patients and Methods: This is a observational and descriptive study based on the record of patients with RA diagnosed by a rheumatologist. The following variables were collected: age, sex, clinic manifestations, lab tests, imaging studies and treatment received. For data analysis the SPSS program version 25 was used and the association between nominal variables was established through a test bases in Chi square distribution, considering p < 0.05 as the value for statistical significance.
Results: From a total of 637 patients with RA, 66 patients (10.36%) who received a therapy with bDMARD were included. From this group, 92.4% were women with an average age of 52.9 years and with an average of 12 years of disease duration. Most of them (93.9%) were seropositive, 50% were erosive, 40.9% with sequela and 33.3% presented with extra-articular manifestations. 68.2% had at least one comorbidity, being the most frequent: obesity (31.8%), arterial hypertension (31.8%) and diabetes (15.2%). Most of them (78.8%) continued using concomitant methotrexate. 59.1% continued using prednisone with an average dose of 3.3 mg/day and 60.6% used NSAID over the last 3 months. The most used bDMARD was an anti-TNF (71.2%). A third of the patients had to change to a second bDMARD, being the lack of efficacy the most frequent reason for it (68.1%). In this subgroup the average persistence of bDMARD used as a first line was 16.27 months and 18.14, 12.57 and 11.66 months for adalimumab, etanercept and abatacept, respectively. There was an association between the presence of erosions and sequela (p < 0.001), between extra-articular manifestations and sequela (p < 0.002), and between the use of NSAIDs and the lack of efficacy of the first bDMARD (p 0.03).
Conclusions: CHM RA patients present frequent comorbidities; persistence of the first bDMARDb used differs from what has been described in other Latin-American populations.
TREATMENT OF NON-DIGITAL LOWER EXTREMITY ULCERS IN PATIENTS WITH SYSTEMIC SCLEROSIS
Patricia Kachur1. 1Ochsner Medical Center, New Orleans, United States.
Systemic Sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and fibrosis. Non-digital lower extremity ulcers are complication of SSc that are often difficult to treat. Their etiology is unknown, but may reflect chronic vasculopathy, as it is often associated with delayed wound healing (like other chronic leg ulcers). Some had postulated a role for larger vessel venous and arterial disease. Many ulcers remain refractory even after restoration of good blood flow and venous drainage. Our case is about a novel approach to treatment of non-digital ulcers from SSc.
A 51 year-old woman with a history of pancreatic neuroendocrine tumor (with complete resection in 2016), primary biliary cirrhosis, and DMII presented with chronic lower extremity wound/ulcers of 8 months that had progressively worsen. Symptoms began as mild trauma to the area with no healing and were associated with Raynaud’s, sclerodactyly, telangiectasia, and occasional esophageal dysmotility. Patient had failed multiple debridements, antibiotics, and steroids without response. Diagnostic biopsies showed dermal fibrosis with mixed inflammation and reactive changes. Laboratory findings +ANA (1:2560 centromere pattern). +SSA, + mitochondrial antibody. Negative Scl70 and RNA-polymerase III Ab, antiphospholipid antibodies, normal complement levels. Vascular studies were all normal. Given data, treatment for SSc was started with pentoxifylline 400mg TID with wound healing in 2 weeks follow up.
The prevalence of non-digital lower extremities ulcers in SSc patients is ~4%. No standard treatment has been established for this syndrome. Thus far, there is only one case published case report of using pentoxifylline resulting in resolution of wound ulcer. This is the second such case.
EFFECTIVENESS AND SAFETY OF TOCILIZUMAB BASED ON CLINICAL AND ANALYTICAL DATA IN PATIENTS WITH RHEUMATOID ARTHRITIS FROM QUITO-ECUADOR
Fernando Naranjo-Saltos1, Alexander Cedeño1, Karen Pozo Medina1, Heidi Angela Fernandez1, and Andrea Lucía Cevallos1. 1Servicio de Medicina Interna. Hospital de Especialidades Eugenio Espejo, Quito, Ecuador.
Background: The use of biological therapy in Ecuador has achieved clinical and analytical goals in disease activity control. Tocilizumab, is an approved therapeutic option in this country.
Objectives: To describe the baseline clinical and laboratory data of 48 patients with rheumatoid arthritis (RA) treated with intravenous tocilizumab and analyze results from follow-up visits in a real-life scenario.
Methods: This is a descriptive study that analyzes the clinical and laboratory data of 48 patients with RA treated with intravenous Tocilizumab from November 2012 to December 2019 in the Autoimmune Disease Unit of a tertiary hospital in Quito-Ecuador.
Results: Data were collected from 45 (93.6%) women and 3 (6.4%) men with a diagnosis of RA. The average age was 41.7 years with a standard deviation (SD) of 13.2 years. The average time from diagnosis to treatment with tocilizumab was 10.9 years with a SD of 5.6 years. At the onset of treatment, the mean value of anti-CCP antibodies was 657.09 U/ml and rheumatoid factor was 403.49 IU/ml. Initial CRP levels averaged 23.04 mg/L with a SD of 33.05 while the erythrocyte sedimentation rate (ESR) was 28.11 mm/h with a SD of 16.17. The initial mean DAS28 score was 6.13. The average years of treatment with the IL-6 inhibitor was 4.1 years.
Data cut off was set at 48 months after initial treatment with tocilizumab; 2 therapeutic failures, 1 death due to intestinal perforation and 3 patients with recurrent infections were reported. The average CRP was 2.6 mg/L with a SD of 5.09 and an average ESR of 11.65 mm/h with a SD of 11.64. The mean DAS28 score was 2.17.
Conclusion: In a real-life scenario the intravenous IL-6 inhibitor tocilizumab, can be considered an effective and safe therapeutic option, with few events relating to infections. It may therefore be maintained on a long-term basis.
TYPIFICATION OF HUMAN LEUKOCYTE ANTIGEN SEROTYPES IN PATIENTS WITH SPONDYLOARTHROPATHIES IN A RHEUMATOLOGY CENTER OF GUATEMALA
Marlon Arita Alvarado1, Licda Ella Rosales1, Valeria Rodríguez1, Gilbert Martínez1, Nilmo Chávez1, Silvia Rivera1, and Estuardo Anzueto1. 1Instituto Guatemalteco De Seguridad Social, Guatemala, Guatemala.
Objective: To typify the different serotypes of human leukocyte antigen (HLA) in spondyloarthropathies in a rheumatology center in Guatemala.
Methods: Different serotypes of HLA were analyzed by microlymphocytotoxicity antigen detection method in 23 patients who met the ASAS and CASPAR criteria for ankylosing spondylitis (SpA) and psoriatic arthritis (PsA) respectively. Frequencies and percentages were used to describe results and demographic data.
Results: The mean age of the patients was 40.6 years, 56.5% were female and 56.5% had a diagnosis of SpA. 56.5% were positive for HLA-B27. 60% of patients with PsA were positive for HLA-B27 and 54% for SpA. 95% were treated with biological disease modifying antirheumatic drugs (bDMARD) and the positivity for different HLA serotypes in PsA was 70 % for HLA-B35, 60% for HLA-B57 and 60% for HLA-B27, in the SpA group 61.5% for HLA-B38 and 53.8% for HLA-B27.
Conclusions: The positivity for HLA-B27 in PsA group was 60% and in SpA group was 53.8%. The prevalent serotypes in PsA were HLA-B35 (70%), HLA-B57 (60%), HLA-B27 (60%) and in the SpA group were HLA-B27 (53.8%) and HLA-B38 (61.54%).
IS STRESS A TRIGGER FOR THE DEVELOPMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS?
Yessika J. Soria Curi1, Ana Lucía Barbaglia1, Luciana Gonzalez Lucero1, María Constanza Bertolaccini1, Héctor Raúl Sueldo1, Susana Mazza1, María Lilia Leguizamón1, Vanesa Espasa1, Mariana Pera1, and Verónica Inés Bellomio1. 1Hospital Ángel C. Padilla, San Miguel de Tucumán, Argentina.
Introduction: Systemic Lupus Erythematosus (SLE) is usually associated with multifactorial psychological stress. Although stress has been considered a “trigger” for the occurrence flares in the connective tissue diseases, there is controversial evidence of the association between stress and the diagnosis of SLE.
Objectives: To assess the frequency of stressors and vital events in patients with SLE and their relationship with SLE diagnosis.
Materials and methods: A descriptive cross-sectional study was conducted. Patients older than 18 years of age with SLE diagnosis (ACR/SLICC criteria), being cared for at the Rheumatology Unit between May and August 2019 were included; 101 patients without any autoimmune disease were also included. Demographic and disease-related variables were studied. The Holmes and Rahe Vital Events scale (43 questions) was used to evaluate vital events and to measure the magnitude of stress that a person has experienced for a given time period and to predict the onset of SLE. The sum of the scores indicates the magnitude of vital stress experienced by a person and the predisposition to acquire a disease. It is classified as: <150: small risk of illness due to stress; 150-299: moderate risk; and ≥ 300: high risk.
Results: 94 patients with SLE were included, of which 94% were women. The mean age was 36.3 ± 10.3 years. 41.9% of the cases had a family history of rheumatic disease and 31.2% of them were unemployed. During the year before the diagnosis of SLE, 48.4% of the patients suffered a stressful situation, the most frequent cause was the death of a close family member (44.1%). Patients with SLE presented significantly higher stress scores than the healthy group (140 ± 27 vs. 45.1 ± 43, p=0.0001); 54.8% of patients with SLE had a score <150; 23.65% between 150-299; and 10.75% ≥ 300. The number of patients with SLE was higher in the moderate and high-risk categories (>150) than the healthy group (34% vs. 2%, p=0.0001). When studying the Holmes and Rahe scale factors individually, patients with SLE had a higher frequency of situations related to: death of the couple’s partner (p=0.029), death of a close relative (p=0.0001), injury or personal illness (p=0.006), change in living conditions (p=0.0001) and poor couple relationship (p=0.017).
Conclusion: Patients with SLE presented high frequency of stressful situations before diagnosis (48.4%), and higher scores compared to the healthy group. The death of a close family member was the most frequent stressful event.
PERSISTENT HYPOCOMPLEMENTEMIA IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
María Lilia Leguizamón1, Yessika J. Soria Curi1, Susana Mazza1, Gabriela Vanesa Espasa1, Francisco Javier Huttmann1, Héctor Raúl Sueldo1, Ana Lucía Barbaglia1, Luciana Gonzalez Lucero1, María Constanza Bertolaccini1, Mirta Santana1, Liliana Galindo1, and Verónica Inés Bellomio1. 1Hospital Ángel C. Padilla, San Miguel de Tucumán, Argentina.
Introduction: Systemic lupus erythematosus (SLE) is a systemic, chronic, autoimmune disease of unknown cause characterized by a wide variety of clinical manifestations and autoantibody production. Complement is useful in the initial diagnosis, as an activity marker and for the follow-up of patients with SLE. Individual components may fluctuate only slightly with disease activity and C4 may even remain low during remission. Hypocomplementemia is associated with renal involvement, cutaneous vasculitis, diffuse alveolar hemorrhage, however, patients with persistent hypocomplementemia are not characterized yet.
Objectives: 1) Determine the prevalence of persistent hypocomplementemia in patients with SLE.
2) Identify clinical characteristics, disease activity and accumulated damage in these patients.
Materials and Methods: A longitudinal study was conducted with a review of the medical records of patients diagnosed with SLE (ACR criteria 82/97) who attended the Rheumatology Service between January 2000 and December 2015. Patients with a minimum follow up time of 6 months from the diagnosis of SLE with quarterly controls and monitoring for 2 years. Persistent Hypocomplementemia (PHC) was defined at C3 and / or C4 values below the normal range of the reference laboratory in a sustained form for at least 24 months. Demographic variables, clinical manifestations, disease activity by SLEDAI 2k, flare by SELENA SLEDAI and accumulated damage by SLICC / SDI were analyzed.
Results: The clinical records of 254 patients with SLE were reviewed and 144 were included; 96% were women, with a mean age at diagnosis of SLE of 30.5 ± 11.2 years and a time of evolution of the disease at the last control 11.85 ± 7.8 years. Forty-one patients had PHC (28.5%; 95% CI 21.1, 35.8). The median disease duration at at the time of PHC was 1 year (0-24) and the mean time of persistence of hypocomplementemia was 56 ± 46 months. In the univariate analysis, PHC was associated with hematological involvement during the course of the disease (p=0.01). Patients with PHC had a higher frequency of severe flares during follow-up (p=0.02). PHC was not associated with the age of onset of SLE, disease activity (maximum SLEDAI reached), accumulated damage or death. Applying Logistic Regression Model with dependent variables with a level of significance <0.25, PHC was associated independently with hematological compromise (OR 3.2).
Conclusion: In this cohort of patients, the prevalence of PHC was 28.5%. PHC was associated with severe flares and hematological involvement.
THE EOSINOPHILIA SPECTRUM IN A REAL WORLD SETTING: ARE WE MISSING EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS DIAGNOSES?
Nicolas Marin Zucaro1, Marina Scolnik1, Valeria Scaglioni1, Nicolas Alvarado1, Gelsomina Alle1, and Enrique R. Soriano1. 1Hospital Italiano De Buenos Aires, Ciudad Autónoma Buenos Aires, Argentina.
Background: Eosinophilic granulomatosis with polyangiitis (EGPA) belongs to a group of diseases characterized by eosinophilia with overlapping manifestations. Classification and study of patients with eosinophilia is challenging and many of them remain without a definite diagnosis. Moreover, EGPA patients may have different phenotypes, with and without vasculitic manifestations. Our objective was to examine patients seen at our hospital with confirmed eosinophilia.
Methods: Patients from a university tertiary hospital with an eosinophilic absolute count greater than 1500/mm3 in the laboratory database, and a second confirmatory count one month apart, between 2002-2018, were included. Electronic medical records were manually reviewed and clinical features (asthma, allergy, non-vasculitic manifestations, vasculitis features and surrogates), diagnostic tests and treatments received were recorded. After reviewing electronic medical records, patients were classified in 6 groups: Primary Hypereosinophilic syndrome (with confirmed mutation in FIP1L1/PDGFRA), eosinophilia without systemic manifestations, eosinophilia with systemic non-vasculitic manifestations, eosinophilia with vasculitic manifestations, secondary causes (parasites or other infections, drug reactions, other neoplastic or hematological disorders, allergic disorders, etc), or insufficiently studied (lack of specific studies that allow classification into secondary causes or systemic manifestations). Fulfillment of different EGPA criteria (1990 ACR, Lanham modified and provisional DCVAS new criteria) was examined.
Results: A total of 459 patients were included (22 with eosinophilia without systemic manifestations, 33 with systemic non-vasculitic manifestations, 4 with vasculitis, 180 with secondary causes and 218 insufficiently studied). No patient was found with a confirmed FIP1L1/PDGFRA mutation. Characteristics of each group of patients are shown in table 1. 133 patients (28.9%) received corticosteroids. None of the patients received omalizumab or mepolizumab. Secondary causes of eosinophilia were: infections (n=45), drug reactions (n=21), hematological disorders (n=59), immune diseases (n=8), allergic conditions (n=41) and others (n=6). All 4 patients with vasculitic manifestations fulfilled Lanham and provisional new DCVAS criteria and were diagnosed as EGPA by the treating physician. Of the 33 patients with eosinophilia with systemic non-vasculitic features, 7 (21.2 %, 95% CI 10.3 -38.6) fulfilled any of the Churg Strauss criteria, and only 3 (9.1%) were diagnosed as EGPA.
Conclusions: the majority of patients with eosinophilia seen at our hospital were insufficiently studied. Patients with vasculitis manifestations are clearly diagnosed as EGPA by the treating physician while in those with systemic non-vasculitic features only 9.1% were classified as EGPA.
INTERSTITIAL LUNG DISEASE ASSOCIATED WITH ANCA-VASCULITIS, CLINICAL SERIES ON 13 CHILEAN PATIENTS
Juan Hormazabal1,2, Monica Gutierrez-Claveria1, Sebatian Ahumada1, Elena Jarpa1, Claudia Valenzuela1, Mauricio Leissner1, Carlos Niklander1, Mario Santamarina1, Helmuth Goecke1,2, Miguel Gutierrez-Torrez1,2. 1Hospital Naval Almirante Nef, Viña del Mar, Chile, 2Universidad de Valparaíso, Viña del Mar, Chile.
Background: In recent years an association between interstitial lung disease (ILD) and ANCA-associated vasculitis (AAV) has been documented, especially in those positive for ANCA specific for myeloperoxidase (MPO).
Objective: To describe clinical, laboratory, imaging and lung function features, and treatment on patients with ILD associated with AAV.
Methods: We examined the clinical records of 13 patients with ILD associated with AAV from our hospital.
Results: Seven patients were female (62%). The mean age at diagnosis was 70 (52-82) years. ILD was diagnosed earlier than AAV in 7 cases (54%); simultaneously in 3 cases (23%); and during AAV follow up in 3 cases (23%). In ten patients (77%) the clinical phenotype was microscopic polyangiitis (MPA) and in 3 patients (23%) was granulomatosis with polyangiitis (GPA). The most common clinical manifestations were pulmonary symptoms (100%), followed by renal involvement (69%), peripheral neuropathy (31%), ear nose and throat symptoms (15 %), skin manifestations (1 patient) and prolonged fever (1 patient). ANCA specificity was MPO in 10 cases (77%) and PR3 in 1 case; one patient had atypical ANCA and 1 patient was ANCA negative (localized GPA).
The tomographic pattern was nonspecific interstitial pneumonia (NSIP) in 7 cases (54%) and usual interstitial pneumonia (UIP) in 6 cases (46%). The initial FVC was normal in 7 patients (54%), mildly restricted in 3 patients (23%) and moderately restricted in 3 patients (23%). The initial DLCO was moderately reduced in 6 patients (46%), mildly reduced in 5 patients (38%) and normal in 1 patient.
The induction treatment consisted of iv methylprednisolone (7 patients), rituximab (5 patients), cyclophosphamide (4 patients), mycophenolate mofetil (1 patient), azathioprine (1 patient) and methotrexate (1 patient). All patients received prednisone. The maintenance therapy included azathioprine (38%), mycophenolate (15%) and methotrexate (15%); four patients received only prednisone.
The mean follow-up time was 73 (2–144) months. Two patients died, 2 months and 3 years after the diagnosis, respectively, both due to respiratory failure. Nine patients remained inactive at the end of the follow-up. Two patients were lost follow-up. Six patients had improvement or stability in lung function at follow up whereas in 3 patients their lung function got worse.
Conclusion: In our series, the ILD associated with AAV was more common in ANCA-MPO vasculitis. In addition to lung disease, renal involvement was the most frequent. The imaging pattern was equally distributed between UIP and NSIP. In the majority of patients ILD occurred concurrently or predated the diagnosis of AAV
FACTORS ASSOCIATED WITH CARDIAC INVOLVEMENT IN SYSTEMIC SCLEROSIS. EVALUATION IN A COHORT OF 139 PATIENTS
Alan Raschia1, Pierina Sansinanea1, Mercedes Argentina Garcia1, Adriana Testi1, Maria Victoria Martire1, and Lucila Garcia1. 1Higa San Martín De La Plata, La Plata, Argentina.
Objective: To determine the frequency of cardiac involvement in patients with Systemic Sclerosis and evaluate the factors associated with its presence.
Material and Method: Patients with systemic sclerosis (SS) were included according to ACR 1980 and / or ACR / EULAR 2013 classification criteria being cared for at a third level hospital, from 1983 to July 2019. Demographic, clinical variables, laboratory data and causes of death were examined. The cardiac manifestations that were evaluated were diastolic dysfunction, systolic dysfunction, pericardial effusion, arrhythmias, dilated right cavities and ischemic heart disease. Descriptive statistics were performed, quantitative variables were expressed as mean, Standard Deviation (SD) or median and interquartile range (IQR), qualitative variables as%. The characteristics of the patients with and without cardiac compromise were compared by Students’tTest or Mann Whitney and Chi Square or Fisher's Exact Tests. Binary logistic regression was performed using the presence of cardiac involvement as a dependent variable.
Results: 139 patients were included, of which 121 (87%) were women, with a mean age at diagnosis of 47.5 years (SD 15). The disease duration was 4 (IQR) years. Of the total patients, 48.2% had some type of cardiac compromise, being 66.7% male, with an average age of 50.46 (± SD 14.23). Regarding cardiac manifestations, 26 patients (18.7%) had diastolic dysfunction, 16 (11.5%) ischemic heart disease, 10 (7.2%) dilated right cavities, 9 (6.5%) pericardial effusion, 7 (5%) systolic dysfunction and 6 (4.3%) arrhythmias. Table 1 shows the bivariate analysis. Older age, pulmonary involvement, the presence of pulmonary arterial hypertension (PAH) and diffuse subtype were significantly associated with the development of heart disease. In the multivariate analysis, PAH was the only variable independently associated with cardiac involvement [OR 6.44 (95% CI 2.04-20.35); p 0.001].
Conclusions: Cardiac involvement was detected frequently, predominantly in the form of diastolic dysfunction. Pulmonary arterial hypertension was associated independently with the development of cardiac involvement. Therefore, we consider searching for diastolic dysfuntion, even in asymptomatic cases.
MUSCLE MASS IS OVERESTIMATED WHEN USING PREDICTION EQUATION FOR MUSCLE MASS IN RHEUMATOID ARTHRITIS
Rafaela Espírito Santo1,2, Leonado Santos1,2, Lidiane Filippin3, Priscila Lora4, and Ricardo Xavier1,2. 1Universidade Federal do Rio Grande Do Sul, Porto Alegre, Brazil, 2Serviço de Reumatologia do Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 3Universidade La Salle, Canoas, Brazil, 4Universidade do Vale do Rio dos Sinos, São Leopoldo, Brazil.
Objective: To compare the anthropometric equation that estimates total-body skeletal muscle mass (SMM) with body composition measurements derived from DXA in RA patients.
Method: Ninety patients diagnosed with RA according to ACR/EULAR criteria were recruited. Body composition was assessed by total body dual-energy x-ray absorptiometry (DXA) for measurement of appendicular lean mass index (ALMI, kg/m2). The prediction equation for muscle mass proposed by Lee et al (variables included: body weight, height, age, sex and race) was used to generate estimates of SMM, stratified by BMI. Frequency analysis, independent Student's t test and intraclass correlation coefficients (ICC) were performed. Statistical significance was considered as p<0.05.
Results: Of the 90 patients included, 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. The mean BMI was 27.39±5.14. Thirty (33.3%) RA patients had normal weight, forty patients (44.4%) were overweight and twenty patients (22.2%) were obese. In normal weight patients, just like overweight and obese patients, the estimates of SMM obtained by Lee equation were higher than those obtained by DXA measurements (Obese: Lee 10.66±1.19 vs DXA 7.10±0.73; Overweight: Lee 8.63±0.99 vs DXA 6.57±0.82; Normal weight: Lee 7.14±0.85vs DXA 6.03±0.71; p<0.05). The Lee prediction equation estimates showed ICC of 0.78 (0.66 - 0.85) with DXA measurements. When stratified by BMI, the Lee equation showed ICC of 0.87 (0.72 - 0.94) for normal weight, 0.83 (0.68 - 0.91) for overweight and 0.77 (0.42 - 0.90) for obese with DXA.
Conclusion: The muscle mass index by Lee prediction equation overestimates the muscle mass in overweight or obese RA patients compared to DXA. Thus, sarcopenic RA patients may be wrongly classified as normal by this equation. This is probably related to the obese cachexia that these patients often present. More studies are necessary to examine better prediction equations for muscle mass in RA patients.
FREQUENCY AND PATIENTS BELIEFS ON VACCINATION IN RHEUMATIC DISEASES
Malena Viola1, Gonzalo Rodriguez1, Alejandro Benitez1, Cecilia Garbarino1, Federico Benavidez1, Claudia Peón1, Gimena Gómez1, Eliana Blanco1, Hernan Molina1, Griselda Redondo1, María Celina de la Vega1, Darío Mata1, Martín Riopedre1, and Osvaldo Messina1. 1Hospital Argerich, Vicente López, Argentina.
Objective: Infectious diseases are increased in patients with rheumatic disorders; vaccination improves morbidity and mortality. The aim of this study was to describe the frequency of vaccination in patients with rheumatic disorders and to compare the results with those obtained in 2009 and 2013 in a similar population. We also identified factors leading to lack of vaccination and patients’ beliefs on vaccines.
Methods: Multicentric cross sectional study in patients with autoinmune diseases from ambulatory rheumatology offices. Evaluation of vaccination status and patients´ knowledge about vaccines were studied. A comparative analysis was carried out with the series registered in 2009 and 2013 in a similar population.
Results: 179 patients (158 female, 88.3% and 21 male, 11.7%) were evaluated. Median age was 52 years. Main pathologies were: Rheumatoid Arthritis 65.9% (n:118), Systemic Lupus Erythematosus 11.7% (n:21), Systemic Sclerosis 3.9% (7), Sjogren Syndrome n = 3.4% (n:6), other diseases 15% (n: 27). Median disease duration: 8.87 years. Ninety three percent of patients (n:167) were taking immunomodulators and 36.8% (n: 66) were using oral corticosteroids (20mg/day or less); 26,8% patients (n: 48) were receiving biological therapies. Vaccination frequency in the population was: Influenza 82% (147); 13-valent conjugate pneumococcal 69.3% (124), 23-valent pneumococcal 64.2% (115) and hepatitis B 62% (111). In comparison with the 2009 and 2013 series there was an increase in the rate of vaccinated patients: influenza (82% vs. 39,1% and 74,2% respectively), antipneumococcic (64% vs. 17% and 29%) and hepatitis B (62% vs. 6,7% and 26,7%).
Reasons for non-vaccination were absence of medical indication (41% of patients for hepatitis B; 32% for 23-valent pneumococcal; 38% for 13-valent pneumococcal and 34% for influenza).
139 patients (77, 7%) knew the benefits of vaccines, 164 (91, 6%) thought vaccines are useful; 134 (74,9%) reported that vaccines may decrease dying probability, 155 (86,5%) thought that vaccines are effective to prevent diseases and 149 patients (83,2%) believed that they prevent serious infections. 71 patients (39%) believed that vaccines can lead to serious consequences and 99 (55,3%) that they are more likely to acquire infections than the rest of the population.
Conclusion: The frequency of vaccination has increased since 2009; however, there is still misinformation regarding vaccines risks and benefits. Promotion and information are essential to improve adherence.
PREVALENCE OF HLA-B27 IN A GROUP OF DONORS AND TRANSPLANTED PATIENTS IN A UNIVERSITY HOSPITAL IN COLOMBIA
Daniel G. Fernández-Ávila1, Catalina Villota-Eraso2, Orlando Roa3, and Juan M. Gutiérrez1. 1Pontificia Universidad Javeriana - Hospital Universitario San Ignacio, Bogotá, Colombia, 2Universidad de La Sabana, Bogotá, Colombia, 3Sánitas EPS, Bogotá, Colombia.
Objective: The human leukocyte antigen HLA-B27 is a class I antigen of the major histocompatibility complex that is strongly associated with ankylosing spondylitis and spondylarthritis. The prevalence of HLA-B27 in the general population varies by geographic area; it is around 2% in African and to 10% in Caucasian populations. The objective of this study was to determine the prevalence of HLA-B27 in a transplant and donor population in a Hospital in Colombia.
Methods: Descriptive cross-sectional study included 465 patients from a cohort of patients and donors of heart, kidney and bone marrow transplants. The clinical record of patients who tested positive for HLA-B27 were reviewed and telephone contact was established to ask about personal history of rheumatic disease and inquire about possible articular symptoms.
Results: Four hundred and five subjects between 10 to 80 years of age with an average of 44.9 years (SD ±14.04) were tested for HLA-B27. 21 were positive for HLA-B27, which indicates a prevalence of 4.5% for this population. A higher percentage of cases was found among men (6.5%) compared to women (2%). None of them had a history of rheumatic disease in their clinical history, 4 patients (19%) reported any positive articular symptoms during the telephone contact; these individuals were therefore evaluated by a rheumatologist, ruling out the presence of spondylarthritis or other rheumatic disease.
Conclusions: The prevalence of HLA-B27 in the population evaluated was 4.5%, consistent with the world prevalence documented in the literature. A higher proportion was found in males compared to females. No cases of spondylarthritis or other rheumatic disease were detected in patients positive for HLA-B27.
DERMATOMYOSITIS: A CHARACTERIZATION OF PATIENTS AT SAN IGNACIO UNIVERSITY HOSPITAL (HUSI) 2004-2019
Laura Charry-Anzola1, Adriana Alejo-Villamil1, Melissa Cantillo-Avilez1, Daniel G. Fernández-Ávila1. 1Pontificia Universidad Javeriana - Hospital Universitario San Ignacio, Bogotá, Colombia.
Introduction: Dermatomyositis is an idiopathic inflammatory myopathy characterized by skin lesions; it is the only myopathy with cutaneous manifestations and since these may constitute the first findings of the disease, they must be clearly and timely recognized. Additionally, this entity is considered a heterogeneous disease, due to its clinical presentation, course and prognosis. It can involve different organs and systems (muscle, skin, heart, gastrointestinal tract, lungs). In Colombia, there are few records describing the clinical characteristics of these patients, which is why this study was performed.
Material and methods: Cross sectional descriptive study. Clinical records of patients who consulted at a University hospital in Colombia between January 2004 and December 2019 were reviewed. The records were acquired using databases of the dermatology, rheumatology and dermatopathology units, also patients admitted to the hospital as an emergency or outpatient with CIE10 diagnostic codes associated with dermatomyositis.
Results: 70 patients with a diagnosis of dermatomyositis were identified; they all met the Bohan and Peter classification criteria, with an average age of 43 years (± 15.3). 48 were women (68.5%). Of the total number of patients, 64 had dermatomyositis and 6 amyopathic dermatomyositis (8.57%). 25 patients (35.7%) underwent a muscle biopsy, of which 18 were positive and 2 nonspecific. 32 patients (45.7%) underwent a skin biopsy, 29 were positive. 35 patients (50%) had electromyography, 25 were positive. CK elevation was evidenced in 47 (67.14%) patients and increased transaminase levels in 38 (54.2%).
The most frequent systemic manifestations were: 15 (21.4%) patients with dysphagia, 8 (11.4%) with interstitial lung disease and 6 (8.5%) with pulmonary hypertension. An association with other connective tissue disorders was documented, 6 (8.5%) patients presented scleroderma, 5 (7.1%) lupus, 1 (1.4%) Sjögren and 1 (1.4%) rheumatoid arthritis. 59 (84.2%) patients required at least one hospitalization, an average 1.9 hospitalizations (± 2.4), with a hospital stay of 8.6 days (± 10.15). 6 (8.5%) patients were diagnosed with cancer, 3 with breast, 2 with lung and 1 with colorectal. The most commonly used medications were prednisolone in 64 patients (91.4%), methylprednisolone pulses in 31 (52.5%), azathioprine in 36 (51.4%) and methotrexate in 29 patients (41.4%). 5 patients (7.14%) died, 4 due to respiratory failure, 1 due to neurological causes.
Conclusion: Clinical information of patients with dermatomyositis is presented at a reference hospital in Colombia. The data obtained are consistent with the information from other case series studied worldwide.
SOCIAL NETWORKS AS INFORMATION SOURCES FOR SPANISH-SPEAKING PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Diana Romero-Alvernia1, Julián Barahona-Correa1, Óscar Muñoz1, Ángel García1, Daniel G. Fernández-Ávila1. 1Pontificia Universidad Javeriana - Hospital Universitario San Ignacio, Bogotá, Colombia.
Objective: To establish quantitative and qualitative data on information on systemic lupus erythematosus (SLE) published in social networks for Spanish-speaking patients.
Materials and methods: A YouTube account was created. A convenience sampling was performed based on most viewed videos. Data were obtained during January 2020 using the term “lupus”, only videos in Spanish were included. Videos were assessed by two independent reviewers; κ-coefficient and correlation were calculated. Quality was assessed using the global quality score (GQS) and a popularity index (PI: # views/Time on internet) was calculated. Videos were classified as useful, misleading or patients’ view. The reliability (DISCERN) and comprehensiveness (content score) of useful videos were assessed.
Results: 50 videos were selected, 60% were useful. The most viewed video was “El té de Dios cura el cansancio crónico, la tiroides, artritis, lupus, y vértigo” (2.329.756 views). No correlation between TI and # views was observed. Most useful videos were generated by government/news agencies or university channels/professional organizations, whereas misleading videos were produced by independent users. Differences in “likes” and GQS were observed. PI was higher for useful videos. A moderate correlation was detected for comprehensiveness and GQS. κ-coefficient was not calculable due to the number of null values.
Conclusions: Social networks are an increasing source of health information for patients. Useful information on SLE is common and appears to be more popular. Regulatory policies should be considered.
SOCIAL NETWORKS AS INFORMATION SOURCES FOR SPANISH-SPEAKING PATIENTS WITH RHEUMATOID ARTHRITIS
Julián E. Barahona-Correa1, Diana M. Romero-Alvernia1, Óscar Muñoz1, Ángel García1, Daniel G. Fernández-Ávila1. 1 Department of Internal Medicine, San Ignacio University Hospital – Pontificia Universidad Javeriana. Bogotá, Colombia. 2 Department of Internal Medicine, San Ignacio University Hospital – Pontificia Universidad Javeriana. Bogotá, Colombia. 3 Department of Internal Medicine – Cardiology Division, San Ignacio University Hospital – Pontificia Universidad Javeriana. Bogotá, Colombia. 4 Department of Internal Medicine – Rheumatology Division, San Ignacio University Hospital – Pontificia Universidad Javeriana. Bogotá, Colombia.
Objective: To establish quantitative and qualitative data on information on RA published in social networks for Spanish-speaking patients.
Materials and methods: A YouTube account was created. A convenience sampling was performed based on most viewed videos. Data were obtained during January 2020 using the terms “rheumatoid arthritis”, only videos in Spanish were included. Videos were assessed by two independent reviewers and the κ-coefficient was calculated. Quality was assessed using the global quality score (GQS) and a popularity index (PI: # views/TI) was calculated. Videos were classified as useful, misleading or patients’ view. The reliability (DISCERN) and comprehensiveness (content score) of useful videos were assessed.
Results: 50 videos were selected, only 24% were useful. The most viewed video was “PON ESTO EN TUS ZAPATOS Y DILE ADIOS A LA ARTRITIS” (3.679.397views). No correlation between TI and # views was observed. Most useful videos were generated by government/news agencies or health websites, whereas misleading videos were produced by independent users or for-profit companies. Differences on TI, “likes”, and GQS were observed. PI was higher for misleading videos. A low agreement between reviewers was observed, although moderate correlation was detected for comprehensiveness and GQS.
Conclusions: False information on RA is common and appears to be quite popular. Regulatory policies should be considered and novel reliability assessment tools should be developed.
¿WHAT IS THE CLINICAL VALUE OF THE PRESENCE OF ANTIBODIES TO EXTRACTABLE NUCLEAR ANTIGEN IN PATIENTS WITH LUPUS?
Diana Carolina Fernández Ávila1, Marina Scolnik1, Martin Brom1, Valeria Scaglioni1, and Enrique Soriano Guppy1. 1Hospital Italiano De Buenos Aires, Buenos Aires, Argentina.
Introduction: the presence of extractable nuclear antigen antibodies (antiENA) (Ro, La, Sm, RNP) in patients with systemic lupus erythematosus (SLE) is related to various specific clinical manifestations but the overall clinical value in the course of the disease is not well established.
Objective: to compare the clinical manifestations, treatments received and outcome measures among patients with SLE with positive and negative anti-ENAs.
Material and method: Patients with SLE treated at a University Hospital since 2000, who met SLICC 2012 criteria were included. Two groups were established: those with positive anti-ENA (some positive anti-ENA some time during the follow-up) and those with negative anti-ENAs (all negative anti-ENA during follow-up). Electronic medical records were reviewed and demographic, laboratory, clinical, treatment and outcome data (death and the SLICC Damage Index (SDI) at the end of follow-up) were collected; these data were compared between both groups. A sub-analysis was carried out that compared the group with negative anti-ENAs and anti-dsDNA vs the group with positive antibodies.
Results: Two hundred and thirty six patients with SLE were included [89.4% female sex, mean age at diagnosis 32.3 years (SD 14.8)], 98 of them (41.5%) with negative anti-ENA and 138 (58.4%) with positive anti-ENA (anti-Ro 40.3%, anti-La 17.4%, anti-Sm 30.1% and anti-RNP 16.9%), followed on average 9.4 years (SD 5.1). One hundred percent of the patients presented a positive ANA. Anti-dsDNA antibodies were positive in 60.1% (95% CI 57.4-68.0) of patients with positive anti-ENA and in 36.7% with negative anti-ENA (95% CI 27.7-46.8) (p <0.001). When comparing the groups, no statistically significant differences were observed regarding clinical manifestations (except normal C3 and anti-dsDNA), mortality (4.1% vs. 3.6% respectively, p = 0.86) or in the SDI at the end of follow-up [median 1, IQR 0-2, versus 1, IQR 0-2, respectively, p = 0.88]. Regarding treatment, only patients who received belimumab had a statistically significant difference [1 (1.0%, 0.1-7.0) versus 9 (6.5%, 3.4-12.1) (p=0.04)].
In the subanalysis comparing patients with negative anti-ENA/antids-DNA antibodies and those with positive antibodies [50 (21.2%, 16-26) vs 186 (78.8%, 73-83)], no statistically significant differences were found.
Conclusions: in this cohort of patients, the groups with negative anti-ENA and anti-dsDNA antibodies had overall clinical behavior, mortality and damage at the end of the follow-up similar to the group with positive anti-ENA antibodies.
PERUVIAN CONTRIBUTION TO THE RHEUMATOLOGY SCIENTIFIC OUTPUT: HOW ARE WE DOING?
Paul Jesus Tejada-Llacsa1, Julio Alejandro Cerna-Lopez1, Fiorella Valle-Farfan1, Manuel Ugarte-GIl1,2, and Graciela S. Alarcón3,4. 1Hospital Nacional Guillermo Almenara Irigoyen, Lima, Perú, 2Facultad de Medicina Universidad Científica del Sur, Lima, Perú, 3 School of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 4Universidad Peruana Cayetano Heredia, Lima, Perú.
Objective: To conduct a PubMed-base review and critical examination of Peruvian contributions to the worldwide rheumatology scientific output between the years 2010 and 2019.
Methods: PubMed was searched for all manuscripts with at least one Peruvian-affiliated author for the 2010 to 2019 years. Duplicate manuscripts were excluded as were those in which the subject was outside the area of rheumatology. Each manuscript was evaluated by two independent assessors (PT, JC); discrepancies were resolved by consensus. The year of publication, manuscript type, institutional and country affiliation, study design, journal quartile (according to SCImago), area of investigation and number of citations were extracted. We used median (p25, p75) and percentages for descriptive analysis. In order to explore the association with manuscripts published in Q1 category Journals, we estimated crude and adjusted prevalence ratios (PR) with 95% CI from Generalized Linear Models (GLM) with Poisson family, log link and robust variance.
Results: Our search lead to a total of 1923 manuscripts; 1688 were excluded because they did not have a Peruvian affiliation. 97 duplicated manuscripts as well as 50 outside the field of rheumatology were also excluded; thus, the data set for these analyses consists of 94 manuscripts. Of them, 51 (52.3%) were published over the last 3 years, 56 (59.3%) of the total were original manuscripts. Universities and Social Security System Hospitals were the institutions with the highest participation in the total number of manuscripts [72 (76.6%) and 58 (61.7%) respectively]. In 48 (51.1%) manuscripts there was a Peruvian-affiliated first author. Seventy-four (78.7%) had at least one non-Peruvian affiliated author; 23 (24.5%) were multicentric studies and 49 (52.1%) were published in Q1 Journals; systemic lupus erythematous was the area most frequently studied [38 (40.3%) manuscripts]. The median (p25, p75) number of citations for all manuscripts was 1 (0, 3). In regression analysis we found that multicenter studies and the inclusion of at least one non-Peruvian-affiliated author were associated with the publication in a Q1 Journal (PRa =2.57, 95% CI:1.04-6.30, p=0.039 and PRa=1.70, 95 % CI: 1.20- 2.41, p=0.002, respectively).
Conclusion: Peruvian scientific production has increased over the last 3 years; the multicenter studies and the inclusion a non-Peruvian author were associated with a higher probability of publication in a Q1 Journal. These data suggest that the Peruvian scientific output to the worldwide scientific rheumatology literature is limited but is increasing and represents a call to action to the Peruvian rheumatology research community.
CYTOMEGALOVIRUS AND HISTOPLASMA INFECTION IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A CASE REPORT AND IMAGES
Diana Katherine Guavita1, Jairo Hernan Cajamarca1, Alejandro Escobar1, Ana Maria Arredondo1, and Hector Hernan Cubides1. 1Fundación Universitaria Ciencias de la Salud, Bogotá DC, Colombia.
Background: Despite the involvement of the immune system in patients with systemic lupus erythematosus (SLE), viral infections are uncommon, with Cytomegalovirus (1) being the main pathogen, followed by fungal infections, with Cryptococcus and Candida (2). So far there are no reports of cytomegalovirus and Histoplasma coinfection in patients with SLE. The objective of this study is to describe the first case in a patient with SLE.
Methods: The medical records of SLE patients with co-infection with cytomegalovirus and histoplasma were reviewed.
Results: A 58-year-old female patient with SLE for 2 years being treated with hydroxychloroquine and azathioprine was admitted to the hospital with a 3-month history of fever, nocturnal diaphoresis and lower respiratory tract symptoms. On physical examination, febrile patient, with cervical lymphadenopathy and hepato-splenomegaly. Laboratory studies showed lymphopenia, anemia and thrombocytopenia, complement consumption, elevation of C-reactive protein, transaminases and bilirubins at the expense of the indirect. She was felt to have active disease, so she was started on methylprednisolone pulses; however, there was no response, so studies were extended to rule out associated infectious processes, bone marrow biopsy was taken, the first one (Figure 1) with atypical lymphoid aggregates CD20 +, without being conclusive. The patient continued to clinically deteriorated, so a second bone marrow biopsy was obtained. It showed reactive lymphoid aggregates. Studies for infections only showed positive viral load for Cytomegalovirus (6830 copies), and treatment with vancyclovir was considered. Despite that, clinical deterioration persisted. Therefore, previous biopsies were reviewed, and the results of the last bone marrow biopsy indicated the presence of mycotic structures compatible with Histoplasma (Figure 2) (had negative antigenuria). Antifungal treatment was started but the patient clinically deteriorated and died. It should be noted that last contralateral biopsy further documents infiltration by mature B cell neoplasia in a diffuse pattern with areas of necrosis (Figure 3).
Conclusion: In patients with autoimmune pathologies, in addition to the suspicion of disease activity, it is important to consider bacterial, viral and mycotic infectious processes in the differential diagnosis, highlighting that there is not enough evidence of adequate diagnostic performance of microbiological tests in patients with autoimmunity to rule out infectious processes, as happens with antigenuria in histoplasma infection (4).
PULMONARY ARTERIAL HYPERTENSION AND RHEUMATIC DISEASES: A POOR PROGNOSTIC COMBINATION
Ignacio Gandino1, Ayelen Rodriguez1, Sophia Lutgen1, Jorge Zambrano1, Litewka Diego1, and Andres Atamañuk1. 1Hospital Fernandez, Ciudad Autónoma de Buenos Aires, Argentina.
Introduction: Pulmonary hypertension (PH) can lead to transplantation and death. Boucly et al developed a simplified risk assessment tool that quantifies the number of low-risk criteria present; it accurately predicted transplant-free survival in PH and may obviate the need for routine invasive hemodynamic follow-up assessment in selected patients. This tool has only been tested in idiopathic, heritable and drug-induced PH.
Objective: To compare the Boucly criteria in patients with idiopathic PH and PH related to connective tissue diseases.
Methods: We reviewed the medical records of all patients with idiopathic PH and PH related to rheumatic diseases who were seen at our Hospital from years 2015 to 2019. Patients were divided in two groups: those with idiopathic PH and those with PH related to rheumatic diseases. Boucly variables were compared between groups. Boucly variables are WHO/NYHA functional class I or II, NT-proBNP < 300 ng/L and 6-min walking distance > 440m.
Results: We included 50 patients with HP, 41 (82%) were female with a mean age at diagnosis of 45.3 years (SD 18.4). Table 1 shows Boucly variables and clinical features. The main autoimmune conditions were lupus and scleroderma. The 6-min walking distance > 440m, basal oxygen saturation, and 6 min walking oxygen saturation resulted in worse results for the group with rheumatic diseases (p=0.02; p=0.03; p=0.03, respectively). Patients with idiopathic disease had a better Boucly prognostic criteria than patients with PH related to rheumatic diseases (OR 5; 95%CI 1.16-24.9; p 0.01).
Conclusion: While other study designs are necessary to assess this tool in this population, this study suggests that the use of these parameters in patients who present PH associated with rheumatic disease could be a good prognostic approach.
NONINFECTIOUS ANTERIOR UVEITIS: ¿WHEN TO SUSPECT SPONDYLARTHRITIS?
Ignacio Gandino1, Sophia Lutgen1, Veronica Casali1, Victor Morales Roldan1, Marcela Bellon1, and Emilio Dodds1. 1Hospital Fernandez, Ciudad Autónoma de Buenos Aires, Argentina.
Introduction: Acute anterior uveitis is the most common form of uveitis, and the majority of these cases are autoimmune. Following idiopathic uveitis, spondyloarthritis (SpA) is the most prevalent cause of uveitis. Many times, rheumatologists and ophthalmologists must work together, to attain a diagnosis of these diseases, to avoid irreversible ocular damage.
Objective: To estimate the variables associated with SpA in patients with non-infectious anterior uveitis.
Methods: We reviewed the medical records of all patients with non-infectious anterior uveitis who were seen at our hospital from years 2004 to 2019. Patients were divided in two groups: those with anterior uveitis with SpA and those with idiopathic and other autoimmune conditions. Clinical features were compared between groups. A multivariable analysis model was used to estimate the association between clinical variables and patients with anterior uveitis related to SpA.
Results: We included 128 patients, 80 (62.5%) females with a mean age at diagnosis of 36.2 years (SD 19.24). The causes of uveitis were: 88 (68.7%) Idiopathic, 22 (17.2%) SpA, 7 (5.5%) sarcoidosis, 5 (3.9%) juvenile idiopathic arthritis, 2 (1.56%) rheumatoid arthritis, 2 (1.56%) ANCA vasculitis, 1 (0.8%) systemic lupus erythematosus, and 1 (0.8%) Vogt-Koyanagi-Harada. Table 1 shows a multivariable analysis between clinical variables and patients with anterior uveitis being SpA the the dependent variable. Non ocular involvement at diagnosis (OR 104.3; IC95% 16.5-657.5; p <0.001) and positive HLA-B27 (OR 15.2; IC95% 2.6-90.3; p 0.003) were associated with anterior uveitis related to SpA.
Conclusion: Non ocular involvement at diagnosis and/or positive HLA B27 have a strong relationship with spondylarthritis. The investigation of both variables in patients with anterior uveitis provides an opportunity to identify patients with SpA. To our knowledge, there is no information of this in our region, and knowing the regional differences and the associated variables is the key to arrive at a final diagnosis. As in other series this study strongly supports the argument for collaboration between rheumatologists and ophthalmologists.
DECREASE IN RF AND ACPA ANTIBODIES IN A LONGITUDINAL COHORT OF RHEUMATOID ARTHRITIS PATIENTS (ONE-YEAR FOLLOW-UP) LOOKING FOR IMMUNOLOGIC REMISSION
Sebastian Magri1, Jessica Torres Chichande1, Einer Sanchez Prado1, Alvaro Ruta1, Dario Aguerre1, Santiago Ruta1, Salvatori Facundo, Dr. and Rodrigo Garcia Salinas1. 1Hospital Italiano De La Plata, La Plata, Argentina.
Objective: To estimate the incidence of decrease in RF and / or ACPA titers after one year of treatment and its association with clinical response. To explore what baseline variables are related to this decrease.
Materials and methods: Patients older than 18 years who entered the Reumacheck program were included. At the first visit the following data were obtained: laboratory studies (RF/ACPA), x-ray films, ultrasound; an interview was conducted (age, sex, schooling, occupation, habits); clinical data; joint counts and HAQ were performed. Each evaluator was blinded to the data of the other tests and evaluations. ACPA levels were measured in titers (IU) and quartiles (1: 0-5, 2: 5-50, 3: 50-200, 4:> 200). At one year the same tests (RF/ACPA) were performed and clinical and treatment data were collected. Statistical analysis: descriptive statistics, Chi square and Fisher exact tests were performed. Student's t test and Mann Whitney. Multiple logistic regression.
Results: 184 patients with RA were included between 2017 and 2019, 83 of them had a second visit a year later; 80% were women, median age 57 years. Decreases in ACPA, RF and both was 50%, 49% and 36%, respectively. The median decreases in titers were: ACPA: 38.7 (2-215) RF: 9.6 (4-85). Baseline variables that predicted decrease of ACPA, RF and both were disease duration of less than 6 months [p= 0.03 RR: 3.2], ACPA quartile 1 p=0.005 RR 0.2, ACPA quartile 3 p=0.016 RR 4, gray-scale synovitis (p=0.003 RR, 4) and power doppler (p=0.001 RR 7) in ultrasonography. Three logistic regression models were peformed, which included the predictive variables, sex, age and treatment; decreases in ACPA, RF and both were associated with disease duration of less than 6 months p=0.007 expB: 9.
The decrease in antibodies was associated with improvement in the CDAI and SDAI (table 1).
Conclusions: The decrease in antibodies occurred in 50% of patients after 1 year of follow-up. This was associated with a shorter time of symptoms duration, high baseline ACPA titers and presence of US activity. In the adjusted analyses, only a shorter disease duration was independently associated. The decrease was also significantly related to positive response of clinical parameters.
HIGH LEVELS OF ACPA AND LOW LEVELS CHOLESTEROL ARE PREDICTORS OF GOOD CLINICAL RESPONSE. PROGNOSTIC FACTORS IN A LONGITUDINAL COHORT OF RHEUMATOID ARTHRITIS (RA) PATIENTS
Sebastian Magri1, Alvaro Ruta1, Santiago Ruta1, Einer Sanchez Prado1, Jessca Torres Chichande1, Salvatori Facundo1, and Rodrigo Garcia Salinas1. 1Hospital Italiano De La Plata, La Plata, Argentina.
Objective: To estimate the proportion of patients who achieve CDAI and SDAI remission and low disease activity and to evaluate the role of baseline ACPA titers and total cholesterol levels in the clinical response.
Materials and methods: Patients older than 18 years who entered the Reumacheck program were included. At the first visit the following variables were obtained: laboratory studies (ACPA-cholesterol), x-ray films, ultrasound, and interview sociodemographic, clinical data (disease duration and comorbidities were collected) ); joint counts and HAQ performed. Each evaluator was blinded to the data from the other studies. ACPA levels were measured in titers and quartiles (1: 0-5, 2: 5-50, 3: 50-200, 4:> 200). A new study visit was carried out every year at which time the same data were collected; In addition, CDAI and SDAI remission and low activity (LDA) were calculated. Statistical analysis: descriptive statistics, Chi square and Fisher exact tests were performed. Student's t test and Mann Whitney. Logistic regression. ROC curve analysis to estimate cut-off values for cholesterol.
Results: 183 patients with RA were evaluated between 2017 and 2019; 83 of them had a new annual visit, 80% were women, average age 56 years. CDAI remission/LDA occurred in22/57% and SDAI remission/LDA in 23/56%
CDAI and SDAI LDA were associated with baseline ACPA (+) 64.4% p=0.05 RR 2.5, ACPA quartile 3-4 76.5% p=0.016 RR 3.3, ACPA titer 79.5 vs 3.95 p=0.04, onset of anti TNF 66% p=0.04 RR 2.6, Cholesterol levels 185 vs 207 p=0.04, HAQ 0.5 vs 0.8 p=0.047. CDAI and SDAI remission (≤ 2.8) were associated only with lower baseline cholesterol levels 170 (38) vs 202 (47) p=0.025.
Two logistic regression models were made, which included the predictive variables, sex, age, dyslipidemia, statin use and treatment: both CDAI and SDAI LDA were independently associated with ACPA quartile 3-4 p= 0.02 expB3 and high cholesterol p= 0.016 expB 0.21. In the ROC curve analysis, the best cut-off value for the baseline cholesterol level predicted by CDAI LDA: AUC 0.67 (0.54-0.8): value 180 (S: 70% E: 50%).
Conclusions: Patients with RA at one year of follow-up reached CDAI - SDAI remission, CDAI-SDAI LDA (%): 21, 22.4, 55.3, 55, respectively. High ACPA titers and low cholesterol levels were associated with the achievement of remission and LDA.
THE CURRENT ROLE OF HLA-B27 IN AXIAL SPONDYLARTHRITIS. PREVALENCE AND PERFORMANCE AS A MARKER IN AN ARGENTINIAN COHORT
Rodrigo Garcia Salinas1, Alvaro Ruta1, Santiago Ruta1, Jessica Torres Chichande1, Einer Sanchez Prado1, Dario Aguerre1, Facundo Salvatori1, and Sebastian Magri1. 1Hospital Italiano De La Plata, La Plata, Argentina.
Objectives: The prevalence of HLA-B27 in Latin America is variable. We aimed at estimating its prevalence in an Argentinian cohort of axial spondylarthritis (axSpA) patients and to evaluate the differences between those positive and negative for HLA-B27 To examine its performance as a diagnostic biomarker.
Materials and methods: Patients with axSpA diagnosis done in a fast-track evaluation program (Reuma-check SpA) between 2017-19 were included. All patients underwent: blood tests, HLA B27, sacroiliac x-ray films, MRI, and ultrasound. Sociodemographic data and symptoms were collected (low back pain: LBP). The clinical assessor was blinded to the complementary studies. For the biomarker analysis, a control group of patients with chronic LBP who were seenat the same place and at the same time were recruited, paired 1:1 (gender and age). Descriptive statistics, Chi square or Fisher's exact tand Students’t or Mann Whitney tests were performed. Logistic regression, and sensitivity, specificity, PPV, NPV and LR were calculated.
Results: 136 patients were included, 68 with axSpA; their characteristics are shown in Table 1. The prevalence of HLA B27 in axSpA patients was 43% (95%CI:30-53). The differences between HLA-B27 positive and negative individuals are shown in Table 2. In the logistic regression: BASFI values and the SpA features showed some differences. When the prevalence of HLA-B27 was compared with that of the control group, the difference was 43% vs 9% OR:7.7 (95%CI: 2.8-24), HLA B27 had a sensitivity: 43%, specificity: 91 %, PPV: 85%, NPV: 58% and LR: 4.9 (95%CI: 3-8).
Conclusions: The prevalence of HLA B27 in axSpA was 43%, positive patients had an earlier age of disease onset, lower BASFI and less SpA features. For the diagnosis of SpA, HLA B27 had a good specificity but low sensitivity.
RHEUMACHECK – SPONDYLARTHRITIS: COMPREHENSIVE FAST-TRACK DIAGNOSTIC PROGRAM: WHAT BENEFITS DOES IT OFFER IN LATIN-AMERICA?
Rodrigo Garcia Salinas1, Einer Sanchez Prado1, Jessica Torres Chichande1, Alvaro Ruta1, Santiago Ruta1, Aguerre Dario1, Salvatori Facundo1, and Sebastian Magri1. 1Hospital Italiano De La Plata, La Plata, Argentina.
Objective: In Latin-America the lack of knowledge, timely referral and access to tests and images are the main causes in the diagnostic delay of the spondylarthritis (axSpA). To evaluate the delay between the onset of symptoms, referral and access to the fast-track diagnosis program and to compare the differential characteristics.
Methods: Patients entering the fast-track diagnostic program were included according to the following criteria: peripheral arthritis plus at least one SpA feature or chronic low back pain (LBP) that began before age 45. Patients underwent on the same day: blood test, HLA-B27, sacroiliac X-ray films, MRI and ultrasonography. Sociodemographic data, characteristics LBP, laboratory features were also recorded. The clinical evaluator was blinded to the complementary studies. Previously, a plan of awareness was made to the local community, physicians and health care personnel involved (media campaigns and referral talks). Descriptive statistics were carried out and, Chi square and Fisher’s exact tests and Student’s t or Mann Whitney tests were applied.
Results: 199 patients were included in program, 137 with axial (table1) and 62 with peripheral symptoms (100% met criteria for PsA). SpA feature: 77% psoriasis, 10% uveitis, 3% IBD, family history: 70% psoriasis, 15% SpA, 10% IBD. The patients with axial symptoms 50% met ASAS criteria. 25% of patients with a diagnosis were referred after the awareness campaign and 55% attended because of social media awareness.
Conclusion: The delay from the onset of symptoms and access to the program was 3 years, the delay of referral was less than one month, 70% came into the program after the awareness campaign. Patients with axSpA diagnoses had distinctive clinical, laboratory and imaging features.
MONOCLONAL GAMMOPATHY IN PSORIATIC ARTHRITIS
Vanessa Ocampo1, and Dafna Gladman1. 1University Of Toronto, Toronto, Canada.
Background: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant clonal plasma disorder, defined by the presence of a serum monoclonal protein (M-protein) at a concentration <30 g/L, a bone marrow (BM) plasma cell percentage <10%, and absence signs and symptoms related to multiple myeloma (MM). The prevalence of MGUS in psoriatic arthritis (PsA) has been reported to be higher than the general population. However, no follow-up is available to determine whether these patients progress to MM.
Purpose: To determine the current prevalence of MGUS in the PsA cohort, evaluate the outcome of patients PsA – MGUS and determine any association of MGUS development and TNF inhibitors.
Materials and Methods: Included were patients followed at the PsA Clinic between January 2008 to January 2018. All patients fulfilled the CLASsification for Psoriatic Arthritis (CASPAR). MGUS was defined as the presence of a discrete band in the gamma- globulin region on at least 2 separate serum protein electrophoresis tests, performed 6 months apart. MM was the outcome of interest. Data extracted from our database included demographic variables, ESR level, use of conventional disease modifying antirheumatic drugs (cDMARD) and Biologic DMARDs (bDMARDs).
Analyses included descriptive statistics [mean (SD) for continuous variables and frequency (percent) for categorical values]. Patients with MGUS were compared to those without using t -test, Wilcoxon test and Fisher test.
Results: Of the 883 patients assessed, 46 (5.3%) had evidence of MGUS on at least 2 separate blood tests. At the time of diagnosis 55.5% of patients were already on bDMARDs. Patients with MGUS had mean PsA duration of 14 years, were less likely to use DMARDs (30%), had more damage joints (24%), higher ESR levels (p=0.0001), but equal number of actively inflamed joints compared to the control group. 1 patient evolved to MM. Both groups were similar in gender, race (Caucasian) and ages of PsA and PsO diagnosis.
Conclusion: The prevalence of MGUS among our cohort of patients with PsA was 5.2%, higher than the prevalence in whites (1.5% – 3%), but lower than the 9.7% reported by Eder et al. only 1 patient progressed and died of MM, less than that expected in the general population. The presence MGUS was associated with measures of disease activity/severity (higher ESR levels and more damaged joints). There was no relationship to bDMARDs.
HIGH RESOLUTION ESOPHAGEAL MANOMETRY AND ESOPHAGEAL MOTOR DISORDERS IN PATIENTS DIAGNOSED WITH SYSTEMIC SCLEROSIS
Ana Beron1, Zully Marengo1, Diego Marino1, Maria Jose Lopez Meiller1, Maria Marta Piskorz1, Jorge Olmos1, Diana Dubinsky1, Natalia Perrota1, and Maria Milena Pertuz1. 1Hospital De Clínicas José De San Martín, Buenos Aires, Argentina.
Abstract: In systemic sclerosis more than 90% of patients experience some gastrointestinal (GI) symptom and it is considered the third clinical manifestation after Raynaud's phenomenon (FR) and cutaneous involvement.
High-resolution esophageal manometry (HRM) is a diagnostic tool that characterizes the functional alterations of the esophagus: absence or decrease of lower esophageal sphincter pressure (LES), failure to coordinate esophageal peristalsis and LES relaxation and contractions of low amplitude or aperistalsis of the lower esophageal third.
Objective: To determine the patterns of esophagus motor involvement by HRM in the different types of scleroderma, and correlate HRM finding with symptoms.
Methods: The study included patients older than 18 years, with a diagnosis of scleroderma (criteria ACR /EULAR 2013), evaluated in Rheumatology and Gastroenterology to whom a HRM was performed, from 2008 to 2016.
The clinical subtype of scleroderma, presence of autoantibodies, demographic characteristics, GI manifestations (heartburn and/or regurgitation, dysphagia, early satiety, nausea /vomiting and postprandial distention) were characterized.
HRM according to usual standards. Esophageal motor disorders were evaluated by the Chicago Classification v3.0, and were defined: Normal peristalsis, hypotony of the lower esophageal sphincter, Absence of esophageal contractility.
Results: Thirty-three patients were enrolled; the median age was 63 years, 94% were female, with female: male ratio of 15:1. 69% had Limited cutaneous systemic sclerosis (lcSSc), 24% Diffuse cutaneous systemic sclerosis (dcSSc) and 6% systemic sclerosis sine scleroderma (ssSSc).
HRM: 7/33 (21%) normal, 23/33 (67%) hypotony of the LES, 14/33 (42%) absence of esophageal contractility.
In the pattern hypotony of the LES, 65% had lcSSc, 30,4% dcSSc and 4,3% ssSSc; with absence of esophageal contractility, 71,5% had lcSSc and 28,5% dcSSc.
GI manifestations: 21 (63%) patients with dysphagia, 26 (78%) heartburn, 24 (72%) regurgitation, 16 (48%) early satiety, 5 (15%) nausea/vomiting and 15 (45%) postprandial distention.
The most frequent GI symptoms in the group of lcSSc were heartburn 19/23 (82.6%), regurgitation 17/23 (74%) and dysphagia 14/23 (61%). In dcSSc dysphagia 7/8 (87.5%), regurgitation 6/8 (75%) and heartburn 5/8 (62.5%). Heartburn and regurgitation were most observed in pathological HRM.
Conclusions: Motor disorders of the esophagus are a frequent manifestation in scleroderma, with the main findings being hypotensive LES and absent peristalsis.
In this study it was observed that the patients with lcSSc had more esophageal involvement determined by HRM compared than the other subtypes of scleroderma.
EARLY RECOGNITION OF PSORIATIC ARTHRITIS. EXPERIENCE OF COMBINED RHEUMATOLOGY AND DERMATOLOGY CLINICS
Veronica Savio1, Carla Alonso1, María Quaglia1, Yohana Tissera1, Susana Pereyra2, Veronica Gallerano2, Alejandra Ruiz Diaz3, Marcela Demarchi1, Agustina Racca1, Carla Gobbi1, Juan Albiero1, Carla Maldini1, Marcelo Yorio1, and Paula Alba1. 1Unidad De Reumatología, Cátedra De Semiología, Hospital Córdoba, FCM, UNC., Córdoba, Argentina, 2Unidad De Dermatología. Hospital Córdoba, Córdoba, Argentina, 3Servicio De Dermatología. Hospital Pediátrico, Córdoba, Argentina.
Background/Purpose: Psoriatic arthritis (PSA) is a chronic inflammatory articular disease and it can develop in 6-39% of Psoriasis (PS) patients. Combined dermatology-rheumatology (D-R) clinics have emerged to optimize integrated care for patients with PS and PSA. Objective: To describe clinical and demographic characteristics of early diagnosis of PSA in a combined D-R Clinics.
Methods: We studied all the patients with PS who consecutively attended to D-R Clinics at Cordoba Hospital from January 2018 to December 2018. All patients who had positive PASE (Psoriatic Arthritis Screening and Evaluation) were evaluated by Rheumatologists. PSA was diagnosed according to the CASPAR criteria. All clinical data were analysed.
Results: Questionnaires were applied to 96 patients. 55,2% were female (mean age 51 years). 52 patients were PASE positive, but 30 patients were evaluated and 26 patients of them fulfilled criteria of PSA.
Conclusion: Combined D-R Clinics facilitate multidisciplinary care of patients with PS and PSA and have been found to improve outcomes, patient and physician satisfaction and efficiency. However, the delay in early diagnosis is still prolonged.
METABOLIC SYNDROME AND PSORIATIC ARTHRITIS. FREQUENCY AND ASSOCIATION WITH DISEASE ACTIVITY
Veronica Savio1, Carla Alonso1, María Quaglia1, Yohana Tissera1, Juan Albiero1, Carla Maldini1, Marcelo Yorio1, Marcela Demarchi1, Viviana Neme1, Carla Gobbi1, and Paula Alba1. 1Unidad De Reumatología, Cátedra De Semiología, Hospital Córdoba, FCM, UNC., Córdoba, Argentina.
Background/Purpose: Psoriasis (PS) is a chronic inflammatory disease and 6-39% of patient with PS develop Psoriatic arthritis (PSA). There is strong evidence linking PSA to increased risk of developing cardiovascular disease. Objective: To study the frequency of metabolic syndrome (MetS) in patients with PSA and its association with disease activity.
Methods: We studied patients with diagnosis of PSA who were cared for at the Rheumatology Unit at Cordoba Hospital from January 2018 to July 2019. PSA was diagnosed according to the CASPAR criteria. Control group was matched by age and gender. Clinical, and laboratory data were collected. The activity of the disease was evaluated by PASI, BSA, DAS 28, DAPSA. The presence of MetS was evaluated according World Health Organization-1998-1999 (WHO), Adult Treatment Panel III-2004 (ATPIII) and International Diabetes Federation-2005 (IDF). PSA cases were analysed in to two groups according to MetS or not diagnosis. p < 0.05 was considered statistically significant.
Results: 23 PSA and 23 controls were included. Data are shown in Table 1, 2 and 3.
Conclusion: MetS seems to be more frequent in PSA and its presence is not associated with disease activity in this group of patients. MetS is a known risk factor for cardiovascular disease, morbidity and mortality in systemic autoimmune diseases. A tight control of this condition in the disease should be recommended.
VALIDATION OF ClinESSDAI FOR ARGENTINA
Maria Florencia Rodriguez1, Anastasia Secco1, Silvia Papasidero2, Lucia Alascio2, Julia Demarchi3, and Sinda Zalles3. 1Hospital Rivadavia, Buenos Aires, Argentina, 2Hospital Tornú, Buenos Aires, Argentina, 3Hospital Británico, Buenos Aires, Argentina.
Introduction: Recently, a new index has been developed to evaluate disease activity in patients with pSS: ClinESSDAI, a tool that has the same domains as the EULAR Sjögren Syndrome disease activity index (ESSDAI) except the biological domain.
Objectives: Validate clinESSDAI in patients with pSS who are cared for at different Rheumatology centers in Argentina.
Design, Materials and Methods: Observational, analytical, cross-sectional study. Translation of the ESSDAI used in its cross-cultural adaptation and validation in Argentina was used.
The purpose of the patients’ first visit to assess the validity of the convergent construct of the instrument. For this and in the absence of a Gold Standard, a VAS on a scale of 0-10 and performed by an expert physician was taken as a reference, to evaluate disease activity by domains of clinESSDAI and global activity of the disease, while another expert physician applied the ESSDAI and ClinESSDAI. The validity of the clinESSDAI was also analyzed by comparing it with the ESSDAI. Ten days later a subgroup of patients, in whom there were no changes in the clinical picture or in the treatment, was seen again; a similar, evaluation was conducted to assesss reproducibility. All physicians were blinded to the evaluation of the other.
Spearman's correlation coefficient was used to assess the correlation between the VAS and the ESSDAI domains, as well as with the total ESSDAI. To demonstrate "equivalence" with the ESSDAI, the clinESSDAI was compared with the ESSDAI using the intraclass correlation coefficient (ICC). The latter was also used to evaluate reproducibility.
Results: The degree of agreement (kappa) was 0.80 among clinESSDAI evaluators and 0.7 among the experts who performed the VAS. We evaluate 47 patients, of which 46 were women (98%). The mean age was 57 years (SD ± 14,13).
The Spearman correlation coefficient (Rho) between the VAS and the domains evaluated of the ClinESSDAI are expressed in Table 1. No patient presented involvement of the muscular domain or the central nervous system. The ICC between the ESSDAI and the clinESSDAI was 0.98 (95% CI: 0.96-1).
CONCLUSIONS: The clinESSDAI proved to be a valid and reproducible tool in our population, and comparable to the ESSDAI.
VALIDATION OF ACR/EULAR PROVISIONAL CLASSIFICATION CRITERIA FOR ANCA-ASSOCIATED VASCULITIS IN A LATIN-AMERICAN TERCIARY CENTER
Victor R. Pimentel-Quiroz1,2, Alfredo Sánchez-Torres1, Cristina Reátegui-Sokolova1,3, Rocío V. Gamboa-Cárdenas1, César Sánchez-Schwartz1, Mariela Medina-Chinchón1, Francisco Zevallos-Miranda1, Erika Noriega-Zapata1, José Alfaro-Lozano1, Jorge M. Cucho-Venegas1, Zoila Rodríguez-Bellido1,4, César A. Pastor-Asurza1,4, Eduardo Acevedo-Vásquez1,4, Risto Perich-Campos1,4, Graciela S. Alarcón5,6, and Manuel Ugarte-Gil1,2. 1Department of Rheumatology. Hospital Nacional Guillermo Almenara Irigoyen. Essalud, Lima, Perú, 2Universidad Científica del Sur, Lima, Perú, 3Universidad San Ignacio de Loyola, Lima, Perú, 4Universidad Nacional Mayor de San Marcos, Lima, Perú, 5Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham, Birmingham, USA, 6Department of Medicine, School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Perú.
Aim: To validate the new classification criteria for ANCA-associated vasculitis (AAV) in a real-life cohort of patients with ANCA associated vasculitis.
Methods: We performed a review of medical records from January 1990 to December 2019 at Hospital Nacional Guillermo Almenara Irigoyen from Peru. AAV was diagnosed by experienced rheumatologists based on the ACR 1990 criteria, Chapel Hill 2012 consensus, EMEA criteria and their experience and clinical acumen. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were diagnosed. Renal limited vasculitis was considered as MPA. To evaluate the performance of new criteria, we classified all patients using the “former criteria set”: the 1990 ACR criteria for GPA and EGPA, and the 1994 Chapel Hill Consensus Conference for MPA. At the same time, we classified all patients using the ACR/EULAR Provisional criteria (new criteria set). The values for sensitivity, specificity and level of agreement (using Cohen’s kappa) of both sets of criteria were calculated, using the clinical diagnosis as gold standard.
Results: Two hundred twelve patients were identified; 12 of them were excluded (eight did not have ANCA and four had incomplete data). Female/male ratio was 1.9:1 [130 (65%)/70 (35%)] and their mean (SD) age at diagnosis was 59.3 (12.6) years. One hundred fifty-four (77%) had MPA, 41 (20.5%) GPA and 5 (2.5%) EGPA. One hundred ninety-six patients had ANCA-IIF results [p-ANCA: 131 (66.8%), c-ANCA: 43 (21.9%), negative-ANCA: 22 (11.3%)] and 190 patients had ANCA-ELISA results [MPO: 129 (67.9%), PR3: 37 (19.5%), negative-ANCA: 24 (12.6%)]. Type of diagnosis according to criteria set used is depicted in Table 1. The new criteria set had better agreement (kappa: 0.653) than the former criteria set (kappa: 0.305). Performance of the criteria sets is depicted in Table 2.
Conclusions: ACR/EULAR Provisional Criteria had better agreement with the clinical diagnosis in Latin-American AAV patients from a real-life cohort.
BIOMARKERS, BIOSIMILARS AND TREATMENT RESPONSE IN RHEUMATOID ARTHRTIS. RESULTS ON A GROUP OF PATIENTS FROM ROMANIA
Bogdan Ion Gavrila1, Claudia Ciofu1, Ioan Ancuta1, Mihai Bojinca1, and Victor Stoica1. 1University Of Medicine and Pharmcy, Carol Davila”, Bucharest, Romania, Bucharest, Romania.
Objectives: The development of bsDMARD therapies emerged from the need to reduce the high cost of treatment with the original molecules in RA patients.
We proposed to test the possible predictive role of RF type IgM and IgA, anti-CCP, anti-mutated citrullinated vimentin (anti-MCV), 14-3-3 eta protein and COMP for treatment response to Infliximab’s biosimilars. We have also assessed the status pretreatment of these biomarkers and the response to treatment as we followed these patients disease course under bsDMARD therapy.
Material and methods: Longitudinal and observational study which include 17 patients followed for 12 months with active RA, uncontrolled by csDMARDS and tus required biologic therapy as per EULAR recommendations.
Clinical assessment was performed at 0, 6 and 12 months according to ACR criteria approved by OMERACT and evaluation of treatment response according to EULAR criteria (good/moderate/nonresponder).
Results: Mean age was 56.59 ± 13.59, all patients being female. After 6 months of treatment, 8 patients achieved a good response and 9 a moderate response.
Following baseline immunological parameters titers and the response at 6 months, general tests have identified significant differences between groups. Tests for identifying differences between the groups showed that lower titers for 14-3-3 eta protein and COMP had predictive value on achieving a good EULAR response at 6 months.
After 12 months of treatment, 1 patient was declared a nonresponder, 3 achieved a moderate response and 12 good response. 1 patient was excluded from the study because of the development of side effects. At this assessment, we did not identify significant differences between the EULAR / 2 categories response after 1 year of treatment and the baseline titers of the biomarkers tested.
We did not identify significant differences between the baseline biomarker status and response to therapy. Values close to the significance were obtained for RF type IgA and response at 12 months, most of the patients with good response being tested negative (good responders 5/12, moderate 3 / 3 and nonresponder 1/1, p = 0.059)
Regarding the serum levels values over time, we noticed a statistically significant reduction of anti-CCP and COMP regarding baseline values.
Conclusion: 14-3-3 eta and COMP could be 2 promising biomarkers for identifying responders and nonresponders to bsDMARD therapies in RA.
RELEVANCE OF THE ABSENCE OF POLYMORPHISMS OF THE GSTM1 AND GSTT1 GENES IN PATIENTS WITH LUPUS NEPHRITIS.
Jairo Alberto Rojano Rada1, Jorge Garrido Bazán2, and Mercedes Fernández Mestre3. 1Centro Biomédico De Investigación En Medicina Interna Hospital Miguel Perez Carreño Caracas, Caracas, Venezuela, 2Postgrado de Medicina Interna, Caracas, Venezuela, 3Instituto Venezolano de Investigaciones Científicas - IVIC, Caracas, Venezuela.
SUMMARY: Objective: To identify whether the absence of the GSTM1 and / or GSTT1 genes is correlated with the response to cyclophosphamide and with the presence of anti-DNA antibodies in patients with lupus nephritis.
Methodology: Correlational cross-sectional study, which included 46 patients diagnosed with systemic lupus erythematosus (SLE), who were cared for at the rheumatology office of the Venezuelan Institute of Social Security - General Hospital “Dr. Miguel Pérez Carreño”, during the period June 2016 - June 2017. Patients with SLE were classified according to the presence or not of renal involvement (lupus nephritis). Five mL of peripheral blood were obtained from each patient for genomic DNA extraction. The presence or absence of the GSTM1 and GSTT1 genes was determined using the multiplex PCR (polymerase chain reaction) method with specific primers. Frequency calculations, descriptive analyses and correlations were carried out with the statistical package SPSS Statistics 17. The correlation result is indicated as a correlation coefficient (r) ranging from +1.0 to 1.0.
Results: In the 46 patients studied, 95.7% were female, with an average age of 31 years. Treatment for these patients included chloroquine in 78%, mycophenolate mofetil in 69.6% and corticosteroids in 38.7%. GST genes were present, GSTM1 + was positive in 100% of patients, with GSTT1 + in 93.5%, GSTT1- only 6.5%. When performing the analysis, positive correlations were found between the SLEDAI score and the presence of anti-DNA antibodies, cyclophosphamide cycles, as well as mycophenolate were correlated with lupus nephritis class (class 3 +4). Likewise, negative correlations were observed between the SLEDAI score and the presence of ANA antibodies, the presence of ANA antibodies with the presence of anti-DNA antibodies, with the class of nephritis and with cyclophosphamide cycles. Other negative correlations observed were the presence of ANCA antibodies with kidney disease and mycophenolate, and finally, the response to treatment with GSTT1.
Conclusion: There is no correlation between the presence of these polymorphisms and the response to treatment with Cyclophosphamide and the presence of anti-DNA antibodies; likewise the absence of these polymorphisms is not evident in the study population unlike in other populations.
Key words: SLE, clinical features, arthritis, erythema, lupus nephritis.
USEFULNESS OF THE 2019 SLE EULAR/ACR CLASSIFICATION CRITERIA IN PATIENTS WITH RHUPUS
Beatriz Frade-Sosa1, Javier Narváez2, Tarek Carlos Salman-Monte3, Vera Ortiz-Santamaria4, Vicenç Torrente-Segarra5, Ivan Castellvi6, Berta Magallares6, Raul Castellanos-Moreira1, Delia Reina7, Sonia Minguez8, Meritxell Sallés9, María Garcia-Manrique de Lara9, Elena Riera11, Sergio Ordonez10, Jose Alfredo Gómez-Puerta1. 1Hospital Clinic, Barcelona, Spain, 2 Hospital de Bellvitge, L'Hospitalet de Llobregat, Spain, 3Hospital del Mar, Barcelona, Spain, 4Hospital General de Granollers, Granollers, Spain, 5Hospital Comarcal de l'Alt Penedès, Vilafranca del Penedès, Spain, 6Hospital Santa Creu i Sant Pau, Barcelona, Spain, 7Hospital Sant Joan de Despi Moises Brogi, Sant Joan Despi, Spain, 8ALTHAIA, Xarxa Assistencial Universitària de Manresa, Manresa, Spain, 9Hospital Parc Tauli, Sabadell, Spain, 10Hospital Arnau de Vilanova, Arnau de Vilanova, Spain, 11Hospital Mutua de Terrasa, Terrasa, Spain.
Background: The concomitant presence of systemic lupus erythematous (SLE) and rheumatoid arthritis (RA) in the same patient is known as Rhupus. Polyautoimmunity is not an uncommon phenomenon, but only a small series of patients with Rhupus has been described. This study aimed at exploring the usefulness of the 2019 EULAR/ACR criteria in patients with Rhupus.
Methods: Cross-sectional study conducted in 11 Catalonian Rheumatology Departments (Spain). We included prevalent cases classified as Rhupus (RA ACR/EULAR 2010 and SLE-ACR 1997). Data of patients with SLE were selected as controls in a ratio 2:1, matched by sex.
Results: 120 patients were included, 40 Rhupus and 80 SLE as controls. 95% were female, with a mean age of 51 years and mean disease duration of 13 years. The 2019 SLE EULAR/ACR criteria were met by 92,5% of the Rhupus and by the 96,3% of the SLE cohort (p>0,05). Excluding the articular domain, there were no differences between those who met the new criteria and the SLE patients (65% Rhupus vs. 77 % SLE (p>0.05)). Using different domains of the criteria among groups, only differences in proteinuria were found (Table).
Conclusion: More than 90% of patients classified as Rhupus criteria fulfilled the new SLE criteria. This study shows that the new 2019 SLE EULAR/ACR criteria are not useful to differentiate SLE and Rhupus patients. Further investigations are needed to measure their usefulness in clinical practice for detecting overlap presentations of RA and SLE.
MATHEMATICAL MODELING AND NUMERICAL SIMULATIONS TO PREDICT THE DEVELOPMENT AND ASSOCIATED COST OF RHEUMATOID ARTHRITIS IN COLOMBIA: A POPULATION-BASED APPROACH
Tommaso Benincasa1, Diego Fernando Aranda1, Consuelo Romero-Sanchez2,3, Lorena Chila-Moreno2,3, Wilson Bautista-Molano2,3. 1Universidad EL Bosque, Faculty of Sciences, Department of Mathematics, Bogotá, Colombia, 2Universidad El Bosque, School of Dentistry, Cellular and Immunology Group, Bogotá, Colombia, 3Universidad Militar Nueva Granada, School of Medicine, Hospital Militar Central/Clinical Immunology Group, Bogotá, Colombia.
Background: Rheumatoid arthritis (RA) is a major cause of progressive joint damage and disability that is associated with a decrease in the quality of life. This condition is also associated with an increasing amount of health care resources overtime. It is estimated that about 250,000 persons may have RA in Colombia. The objective of the study is to assess the development of RA in the Colombian population over the next five-years and to predict the number of new patients and their incidence in terms of direct-costs on the health-care system.
Methods: We use a population-based approach of epidemiological type to examine the development of disease over time. We designed a continuous mathematical model for the transmission and evolution of RA in a population. The description of a physical phenomenon (disease), by differential equations is called mathematical modeling and allows us to not only study and analyze the dynamics of the disease, but also to predict its future development. The system is formed by eight ordinary differential-equations, explaining the influence of the epidemiological parameters considered in the evolution of this condition. This mathematical modeling approach has been extensively used to study the dynamical behavior of diseases in populations from an epidemiological point of view. The parameters of the mathematical-model are estimated using real data from RA prevalence in Colombia. The total population was divided into eight groups named as follows: general population, prevalent (at risk), pre-clinical (asymptomatic), symptomatic (tender and swollen joints), diagnosed without treatment (fulfilling classification-criteria), starting early treatment (before two years of symptoms), starting late treatment (after two years of symptoms), and chronic RA patients (disease duration more than 2 years). Numerical simulations allow understanding and explaining the RA epidemiology and therefore predict the disease's over the next five years in Colombia.
Results: The model shows that over the next five years there will be 129,000 new RA-patients in Colombia, which will have an estimated cost to the healthcare system of about $4125 million (USD).
Conclusion: We investigated the development of RA disease in the Colombian population over the next five years and were able to predict the number of new patients and their incidence in terms of direct costs on the health-care system. The economic impact of RA is considerable not only for the individuals but also for society in general. Optimal strategies with the aim of reducing the economic impact of the disease on the health-care system should be proposed.
HLA-B27 ALLELIC, GENOTYPIC AND HAPLOTYPIC FREQUENCY IN A GROUP OF HEALTHY INDIVIDUALS IN COLOMBIA
Consuelo Romero-Sànchez1,2,3, Natalia Hernandez6, Lorena Chila-Moreno2,3, Juliette De Avila3, JM Bello-Gualtero1,2, Karen Jimenez5, Diana Padilla4, and Wilson Bautista-Molano2,3. 1Hospital Militar Central, Rheumatology and Immunology Department, Bogotá, Colombia, 2Universidad Militar Nueva Granada, School of Medicine, Clinical Immunology Group, Bogotá, Colombia, 3Universidad El Bosque, School of Dentistry, Cellular and Molecular Immunology Group (INMUBO), Bogotá, Colombia, 4Universidad de la Sabana, Rheumatology Program, Chia, Colombia, 5Universidad El Bosque, School of Medicine, Pediatric Rheumatology Program, Bogotá, Colombia, 6Universidad Colegio Mayor de Cundinamarca, Basic Science Faculty, Bacteriology Program, Bogotá, Colombia.
Introduction: Reports of allelic, genotypic, and haplotypic frequencies of the HLA-A,-B,-DRB system have been published in different populations around the world. The HLA-B27 allele mapping has shown that it has a high degree of genetic polymorphism and clinical importance. Only a few reports describe subtypes of HLA-B27 from peripheral blood in a healthy Colombian population.
Objective: To establish the allelic, genotypic, and haplotypic frequency of HLA-B27 in a group of healthy Colombians.
Methodology: Results of peripheral blood of healthy Colombian mestizo individuals in which joint symptoms were ruled out referred to the Immunology laboratory from 2015 to 2018 with request for typing HLA-A, B, DR. The HLA-PCR/SSO LifeCodes typing procedure was performed by multiplexing based on hybridization of probes of the single-stranded DNA obtained, recognizing the polymorphism of the second and third exons of the HLA class-I molecules, analyzed in a LUMINEX IS 100/200 system xMAP® technology. Confirmation of the positive samples of the HLA B 27 allele was performed with Sequencing Technology: Illumina/PacBio Sequencing in HistoGenetics, USA, analyzing the second and third exons. Frequencies (n (%)) were obtained for demographic, genetic variables. (Ethical/Code HMC2018-020).
Results: 255 healthy individuals with a distribution of female gender (49.4%), and male (50.6%) were included. Nine subjects were identified for the HLA-B27* allele for a genotypic frequency of 3.5% and an allelic frequency of 1.8%. Men in 55.6%; 55.6% between 19 and 45 years, followed by over 45 in 33.3%. Their birthplace was four individuals from the department of Cundinamarca, two from the department of Antioquia, two from the department of Boyacá, and one from Cesar department. No individuals were found with two alleles or homozygous for the B27* allele. Sequencing in 33.0% of healthy individuals with the expression of the B27* allele showed in all of them the subtype B*27:05:02g. The most frequent haplotypes associated with B27* were: A*0201-B*2705-DRB*0403; A*2301-B*2705-DRB*0401; A*2402-B*2705-DRB*0101;A*0201-B*2705-DRB*0402 and A*0201-B*2705-DRB*0801.
Conclusion: We report the subtypes of the HLA B27 allele with its allelic and genotypic frequency in addition to the haplotypes in a group of healthy Colombians. These results are consistent with published frequencies in different populations in Colombia, which confirms the existence of racial mix with a high degree of Caucasian influence, also observing the repopulation of the central region of the country explained by migratory phenomena. It is essential to highlight that this is one of the first reports by high-resolution technique of subtypes of HLA-B*27 alleles from peripheral blood in healthy Colombians.
EVALUATION OF THE FREQUENCY OF INTESTINAL PARASITES AND ITS ASSOCIATION WITH CLINICAL MANIFESTATIONS AND ACTIVITY INDICES IN PATIENTS WITH SPONDYLARTHRITIS.
Liliana Morales1, Adriana Beltran-Ostos7, Jacqueline Chaparro-Olaya1, Wilson Bautista-Molano2,4, Paula Hernandez1, Diego Alejandro Jaimes6, Moises León-Falla10, Juliette De Avila2, JM Bello-Gualtero3,4, Alejandro Ramos-Casallas2, Diana A. Acero-Molina4,10, Cesar Pacheco-Tena8, Philippe Chalem-Choueka9, Cristian Florez-Sarmiento2,5, Viviana Parra-izquierdo2,5, Magaly Chamorro-Melo3,4, Consuelo Romero-Sanchez2,3,4. 1Universidad El Bosque, Laboratorio de Parasitología Molecular, Bogotá, Colombia, 2Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia, 3Hospital Militar Central, Rheumatology and Immunology Department, Clinical Immunology Group, Bogotá, Colombia, 4Universidad Militar Nueva Granada, School of Medicine, Clinical Immunology Group, Bogotá, Colombia, 5Gastroadvanced, Bogotá, Colombia, 6Clínicos IPS., Bogotá, Colombia, 7Hospital Militar Central, Scientific Research Unit, Bogotá, Colombia, 8Biomedicina de Chihuahua, Chihuahua, México, 9Fundación Instituto de Reumatología Fernando Chalem, Universidad El Rosario, Bogotá, Colombia, 10Universidad El Bosque, Master in Basic Biomedical Science Program, Bogotá, Colombia.
Background and Objective: Recent studies have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases, as well as its impact on the efficacy of therapeutic agents. It has been postulated that the transition to modern lifestyle is not only associated with a dramatic decrease in the diversity and prevalence of intestinal helminths but also with the increasing prevalence of chronic autoimmune and inflammatory diseases. Therefore, it is necessary to determine if the microbiota associated with intestinal infection represents an important and significant factor concerning the treatment or disease activity in condition such as SpA.
Methods: Cross-sectional study. 62 patients with SpA according to ASAS classification criteria and 45 healthy subjects (HS) were included. Clinical evaluations were made by rheumatologists and gastroenterologists, magnification colonoscopy and histological analysis in patients with ≥2 gastrointestinal symptoms were performed.
Evaluation of most prevalent parasites in Colombia was made by direct light microscopy using three techniques: the direct wet smear, processing by the Kato-Katz kit and Mini Parasep SF fecal parasite concentrator. Lab tests included fecal calprotectin levels, C-reactive protein, sedimentation rate, and HLA-B27. The association between the presence of intestinal parasites with clinical variables, colonoscopy, and histological variables were evaluated using the Chi-square or Fisher's exact tests. (Ethical/Cod.2017-023).
Results: The HS had a mean age of 39.8±14.0, and 60.0% were male while 59.7% of SpA patients were male with a mean age of 45.1±11.3 years; 41.9% were positive for HLA-B27, and 77.4% showed axial involvement. 69.4% were receiving biological treatment, and 67.7% had ASDAS-CRP >2.1; however, 68.0% of patients were positive for >2 gastrointestinal symptoms with a predominance of abdominal pain (66.1%), abdominal inflammation (64.6%), and diarrhea(50.0%). Compared with controls, the parasites in SpA patients did not show a statistical significant difference except for Blastocystis spp and Endolimax nana where 100% of the patients with SpA had more than 10 cysts per field for each parasite (p=0.001 and p=0.005, respectively); 22.7% presented increased levels of fecal calprotectin (p=0.003). Interestingly, 100% of patients with Entamoeba coli infection were positive for HLA-B27(p=0.025). The presence of intestinal parasites in SpA patients was not associated with gastrointestinal symptoms, either disease-activity, treatment, colonic, or pathological changes by colonoscopy in the intestinal mucosa.
Conclusion: The intestinal parasitism in the tropic shows the same pattern in SpA patients as well as in HC. However, the prevalence of Blastocystis spp and Endolimax nana in these patients is striking. The presence of intestinal parasites in SpA does not seem to influence the course and activity of the disease or of its treatment.
CHROMOENDOSCOPY AND MAGNIFICATION COLONOSCOPY CHARACTERIZATION OF MINIMAL FINDINGS IN THE MUCOSA OF THE COLON AND ILEUM AND THEIR ASSOCIATION WITH CLINICAL MANIFESTATIONS IN PATIENTS WITH SPONDYLARTHRITIS AND GASTROINTESTINAL SYMPTOMS
Cristian Flórez-Sarmiento1,4, Viviana Parra-Izquierdo1,4, Wilson Bautista-Molano1,3, Magaly Chamorro-Melo2,3, Adriana Beltran-Ostos8, Diego Alejandro Jaimes5, Alejandro Ramos-Casallas1, Diana Acero-M3,9, JM Bello-Gualtero2,3, Jaiber Gutierrez2,3, Cesar Pacheco-Tena6, Philippe Chalem-Choueka7, and Consuelo Romero-Sanchez1,2,3. 1Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia, 2Hospital Militar Central, Rheumatology and Immunology Department, Clinical Immunology Group, Bogotá, Colombia, 3Universidad Militar Nueva Granada School of Medicine, Clinical Immunology Group, Bogotá, Bogotá, 4Grastroadvanced, Bogotá, Colombia, 5Clínicos IPS, Bogotá, Colombia, 6Biomedicina de Chihuahua, Chihuahua, México, 7Fundación Instituto de Reumatología Fernando Chalem, Universidad El Rosario, Bogotá, Colombia, 8Hospital Militar Central, Scientific Research Unit, Bogotá, Colombia, 9Universidad El Bosque, Master in Basic Biomedical Science Program, Bogotá, Colombia.
Introduction: Narrow Band Imaging is an endoscopic visualization tool also called Digital Chromoendoscopy which, together with the magnification endoscope, allows a detailed evaluation of the mucosal surface and its vascular network, which facilitates the diagnosis and monitoring of early lesions. This technique has demonstrated a better detection, which allows optical diagnosis during a colonoscopy examination. Patients with SpA with nonspecific gastrointestinal symptoms, subclinical intestinal inflammation are defined endoscopically and histologically.
Objective: To detect early structural inflammatory changes by chromoendoscopy and magnification colonoscopy in colonic/ileum digestive mucosa, and establish its association with clinical variables in SpA with gastrointestinal symptoms.
Methodology: Clinical evaluation by rheumatologist in SpA patients (ASAS/criteria), fecal calprotectin levels, and HLA-B*27 were performed. In patients with ≥2 gastrointestinal symptoms clinical evaluation by gastroenterologist, chromoendoscopy, magnification colonoscopy, and histological analysis were performed. The association between clinical and colonoscopy variables were evaluated using the Chi-square or Fisher's exact tests(Ethical/Code.MHC-2017-023).
Results: In total, 62 SpA patients with mean age of 45.1±11.3 years, axSpA (77.4%) pSpA (12,9%), biological treatment (69,4%), ASDAS-CRP>2,1(67.7%), HLA-B27(+) (41.9%) were included. Patients ≥2 gastrointestinal symptoms were found in 67,7%. The most important symptoms were: Abdominal pain (66,1%), abdominal distension (64,5%), food intolerance (59,7%). High level of calprotectin (22,6%). In patients with gastrointestinal symptoms chromoendoscopy and magnification colonoscopy was performed. The mean age of 45.4±10.5, male in 57.6%, BMI>25 in 69,7%, HLA-B*27(+) 39,4%, Former smoker 33,3%, axSpA 84,8% and ASDAS-CRP>21 78.8%. The colonoscopy and chromoendoscopy results are shown in Table 1. In total, 27.27% of the patients presented high levels of calprotectin, of which 66.0% had more than two gastrointestinal symptoms (p=0.015). 77.8% presented alterations in the ileal mucosa (p=0.060). The most frequent alteration was the loss of vascular pattern (p=0.002). By histological analysis, 5 patients had acute ileum inflammation, of them 4 had increased levels of fecal calprotectin (p=0.013). 30.8% of patients were positive for HLAB*27:05:02 and had ulcers in the ileum (p=0.017) and 61.5% had a chronic inflammatory pattern (p=0.020).
Conclusion: Chromoendoscopy provides an enhanced, detailed contrast of the gastrointestinal mucosa surface, mainly in the loss of vascular pattern in the ileum. The active search for symptoms, signs, and biomarkers of gastrointestinal involvement in addition to an objective endoscopic and histological evaluation may offer new perspectives in the evaluation of SpA patients and may provide guidance for specific clinical and therapeutic management.
FREQUENCY OF GASTROINTESTINAL SYMPTOMS AND CHANGES IN THE ILEUM AND COLON MUCOSA AND THEIR ASSOCIATION WITH CLINICAL MANIFESTATIONS AND LEVELS OF CALPROTECTIN: A CROSS-SECTIONAL STUDY IN PATIENTS WITH SPONDYLARTHRITIS.
Viviana Parra-Izquierdo1,4, Cristian Florez-Sarmiento1,4, Diego Alejandro Jaimes5, Magaly Chamorro-Melo2,3, Juliette De Avila1, JM Bello-Gualtero2,3, Alejandro Ramos-Casallas1, Diana Acero-M3,9, Jaiber Gutierrez2,3, Cesar Pacheco-Tena6, Philippe Chalem-Choueka7, Wilson Bautista-Molano1,3, Adriana Beltran-Ostos8, and Consuelo Romero-Sanchez1,2,3. 1Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia, 2Hospital Militar Central, Rheumatology and Immunology Department, Clinical Immunology Group, Bogotá, Colombia, 3Universidad Militar Nueva Granada, School of Medicine, Clinical Immunology Group, Bogotá, Colombia, 4Gastroadvanced, Bogotá, Colombia, 5Clínicos IPS, Bogotá, Colombia, 6Biomedicina de Chihuahua, Chihuahua, México, 7Fundaciön Instituto de Reumatología Fernando Chalem, Universidad El Rosario, Bogotá, Colombia, 8Hospital Militar Central, Scientific Research Unit, Bogotá, Colombia, 9Universidad El Bosque, Master in Basic Biomedical Science Program, Bogotá, Colombia.
Introduction: The Spondylarthritis(SpA) is a group of chronic inflammatory rheumatic diseases, in which 5-10% of extra-articular manifestations are gastrointestinal as in inflammatory bowel disease. Colonoscopic studies in SpA patients show silent ileitis or colitis in 30% to 40% and histologic examination reveals microscopic inflammation in up to 60%. In addition to abnormal levels of intestinal bacteria may stimulate pathological immune responses associated with the persistence of musculoskeletal and intestinal inflammation.
Objective: To detect early structural inflammatory changes in colonic and ileum mucosa in SpA patients with gastrointestinal symptoms.
Methods: A cross-sectional study included 50 patients with SpA, according to ASAS classification criteria. A specific questionnaire was applied, asking for gastrointestinal symptoms. Clinical evaluation by rheumatologist and in patients with ≥ 2 gastrointestinal symptoms clinical evaluation by gastroenterologist, performing digital chromoendoscopy, magnification colonoscopy, and histological analysis. Lab tests included fecal calprotectin, C-reactive protein, erythrocyte sedimentation rate, and HLA B27*. The association between clinical variables and colonoscopy and histological variables were evaluated using the Chi-square or Fisher's exact tests. (Ethical/Cod. 2017-023).
Results: The patients mean age was 44.3±11.6 years, 56.0% were male and 75.5% had high disease activity by ASDASCRP, 60.0% were receiving anti-TNF, 8.0% anti IL-17. In total, 28.2% had ≥2 gastrointestinal symptoms with predominance of abdominal pain and abdominal inflammation (72.0%), diarrhea (58.0%), mucoid evacuation (24.0 %) and 63.0% food intolerance. High levels of fecal calprotectin were found in 22.2%. Colonoscopy findings (Table 1)
In the ileum, 83.3% of patients with high levels of calprotectin had villi atrophy (p=0.003), 50.0% of these patients showed inflammatory infiltrates (p=0.006). All patients with ileum microscopic inflammation showed ASDAS-CRP≥2.1 (p=0.027).
Conclusions: Spa patients with high disease activity have a higher frequency of gastrointestinal symptoms, with relevant abnormalities in the colonic and ileum mucosa. Chromoendoscopy and magnification endoscopy allowed a higher probability of identifying early changes before the onset of severe symptoms and may guide clinical and therapeutic management.
EVALUATION OF THE INTESTINAL MICROBIOME FROM COLON AND ILEUM ASPIRATE OBTAINED FROM A DIGITAL CHROMOENDOSCOPY AND MAGNIFICATION COLONOSCOPY: A NEW ALTERNATIVE
Moisés León-Falla6, Cristian Florez-Sarmiento2,5, Carlos A. Nieto1, Zaida Corredor1, Viviana Parra-Izquierdo2,5, and Consuelo Romero-Sanchez2,3,4. 1Universidad El Bosque, Bacterial Molecular Genetics Laboratory, Bogotá, Colombia, 2Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia, 3Hospital Militar Central, Rheumatology and Immunology Department, Clinical Immunology Group, Bogotá, Colombia, 4Universidad Militar Nueva Granada, School of Medicine, Clinical Immunology Group, Bogotá, Colombia, 5Gastroadvanced, Bogotá, Colombia, 6Universidad El Bosque, Master in Basic Biomedical Science Program, Bogotá, Colombia.
Introduction: The quality and source of the intestinal aspirate directly influence the percentages and diversity of the bacterial population. The stool sample is the one used as the standard for the analysis of the intestinal microbiota. However, such samples do not allow us to differentiate bacterial biodiversity through the gastrointestinal tract.
Objective: To implement a new alternative intestinal aspirate obtained from the colon and ileum through colonoscopy for the evaluation of the intestinal microbiome.
Methods: 10 mL of the sigmoid colon and ileum aspirates were collected from samples derived from a magnification colonoscopy. After centrifugation at 4 degrees Celsius, the precipitate was subjected to enzymatic and mechanical lysis to obtain the total DNA. The extracted DNA was subjected to sequencing of a variable region of the 16S gene, using MiSeq-technology. The processing included a standard positive control, taken from the stoolsof a healthy individual. Data in relative abundances and frequencies were recorded.
Results: The sample was obtained from an 18-year-old female patient with a diagnosis of Crohn's disease. From the collected samples, about 180 thousand readings were obtained for each of the samples with a quality Q20% near 98 and Q30% of approximately 95, indicating a high-reliability value. Regarding the classification of the Operating Taxonomic Unit (OTU),82 and 74 were reported for ileum and colon, respectively. The data revealed a majority abundance for Proteobacteria and Firmicutes; however, percentages varied depending on the source of the sample. An abundance of 42.9% for Firmicutes, 56.4% for Proteobacteria, and 0.7% Actinobacteria was found for the ileum sample; for the colon samples, 61.2% Firmicutes, 36.5% Proteobacteria and 2.3% Actinobacteria. For phylum Bacteroidetes the real abundance was 0%. The results from the healthy control reported 34.0% for Firmicutes, 58.0% for Bacteroidetes, 3.0% Proteobacteria and 5.0% Actinobacteria. A significant decrease in both colon and ileum of the Firmicutes edge, Faecalibacteiurm prausnitzii, with a relative abundance of 0,0%. (Ethical Code-HMC-2017-023)
Conclusion: The colon and ileum aspirates allowed the differential evaluation of the intestinal microbiome versus that of the fecal sample. The percentages varied depending on the source of the sample, demonstrating the diversity of the bacterial population. A complete decrease in the Bacteroidetes phylum was observed, at both the colon and ileum level, and significant increases in the Firmicutes and Proteobacteria phylum compared to the stool sample. Faecalibacteiurm prausnitzii abundance was 0,0% from both samples. The presence of this microorganism has associated anti-inflammatory and protective effects at the intestinal barrier level. Additionally, changes in the bacterial population in ileum and colon are determinants in the sensitization of the immune system for inflammatory bowel involvement due to the influence they have on the production of short-chain fatty acids and the absorption of nutrients.
HLA B*27, ALLELE, GENOTYPIC, AND SUBTYPES FREQUENCIES OF SPONDYLARTHRITIS AND HEALTHY SUBJECTS TYPED BY HIGH RESOLUTION FROM A COLOMBIAN GROUP
Consuelo Romero-Sànchez1,2,3, Wilson Bautista-Molano1,3, Magaly Chamorro-Melo2,3, Adriana Beltran-Ostos6, Juliette De Avila1, JM Bello-Gualtero2,3, Alejandro Ramos-Casallas1, Cesar Pacheco-Tena7, Philippe Chalem-Choueka8, Cristian Fabian Florez-Sarmiento1,5, Viviana Parra-Izquierdo1,5, and Diego Alejandro Jaimes4. 1Universidad El Bosque, Cellular and Molecular Immunology Group/INMUBO, Bogotá, Colombia, 2Hospital Militar Central, Rheumatology and Immunology Department, Clinical Immunology Group, Bogotá, Colombia, 3Universidad Militar Nueva Granada, School of Medicine, Clinical Immunology Group, Bogotá, Bogotá, 4Clínicos IPS, Bogotá, Bogotá, 55.Gastroadvanced, Bogotá, Colombia, 6Hospital Militar Central, Scientific Research Unit, Bogotá, Colombia, 7Biomedicina de Chihuahua, Chihuahua, México, 8Fundación Instituto de Reumatología Fernando Chalem, Universidad El Rosario, Bogotá, Colombia.
Introduction: Spondylarthritis (SpA), are a group of chronic inflammatory joint rheumatic diseases that share clinical, radiographic, and immunogenetic characteristics. The HLA-B*27 plays a role in the etiopathogenesis. The heterogeneity in HLA-B*27 alleles are mentioned as subtypes and determined at a DNA sequence, where some subtypes are associated with the increased disease risk.
Objectives: The aim was to establish the allelic, genotypic, and subtypes frequencies of HLA-B*27 in a group of patients with SpA and a healthy population in Colombia.
Methodology: A descriptive study. Blood samples from Colombian Mestizo individuals diagnosed with SpA by ASAS criteria evaluated by Sequencing Technology: Illumina/PacBio Sequencing with analysis of the second and third exon. Results reported with six digits (including null alleles). The other group-excluded results correspond to healthy individuals with whom joint symptoms. In that group the HLA-PCR/SSO LIFECODES typing procedure performed by multiplexing based on the hybridization of probes of the single-stranded DNA and Sequencing Technology carried out confirmation of the positive samples of the B27 allele. Frequencies obtained by direct accounts for demographic, genetic variables. This study is approved by The Institutional Ethics Committee–HMC 2018-020/2017-023.
Results: 46 SpA patients, of which 60.9% were men, with a mean age of 45.1 ± 12.1 years, 87.0% presented axial commitment. Twenty-one subjects (76.2% male) were positive for the HLA-B*27 allele for a genotypic frequency of 45.7% and an allelic frequency of 22.9%. The 19.6% were subtype B*27:05:02g, and only 3.3% presented the B27:02:01g. In which the 90.5% were axSpA. On the other hand, 255 systemically healthy individuals evaluated, 50.6% corresponded to men. The age range was 19 to 45 years (57.1%), followed by those over 45 years (33.1%). Nine subjects (55.60%. male) were positive for the HLA-B*27 allele for a genotypic frequency of 3.5% and an allelic frequency of 1.8%. The analyzed individuals had not presented two alleles or homozygous for the B*27 allele. All of them resulted in high-resolution sequencing showed subtype B*27:05:02g.
Conclusion: Different subtypes of HLA-B*27 are distributed unevenly worldwide in various ancestries and with different potency of association with SpA disease. The results showed the prevalence of two subtypes common from Caucasians in SpA and only B*27:05:02g in the healthy population. Several genetic composition studies show that the Colombian population has a European, Native American, and African ancestry, which changes according to the geographic location. To our knowledge, this is the first report and analysis performed using a high-resolution level in SpA patients in Colombia.
ANTIPHOSPHOLIPID ANTIBODIES DO NOT IMPACT THE OVARIAN RESERVE IN PREMENOPAUSAL WOMEN
Savino Sciascia1, Massimo Radin1, Elisa Menegatti1, Alice Barinotti, Federica Sini, Irene Cecchi1, Elena Rubini1, Silvia Foddai1, and Dario Roccatello1. 1University Of Torino, Torino, Italy.
Objective: Antiphospholipid antibodies (aPL) have direct negative effects on placentation, where they bind to the trophoblast, reducing its capacity for invasion, and its proinflammatory effects, such as complement activation and neutrophil recruitment, contributing to placental insufficiency, restricted intrauterine growth, and fetal loss. However, whether aPL may be associated with primary infertility, decreasing ovarian reserve, is still on debate.
We aimed to investigate the possible differences in the levels of ovarian reserve between asymptomatic aPL carriers and antiphospholipid syndrome (APS) patients, by measuring the levels of anti-müllerian hormone (AMH).
Methods: We enrolled 69 premenopausal women divided in 3 groups: a) patients with APS, either primary (PAPS) or secondary (SAPS), according to the Sidney classification criteria; b) asymptomatic aPL carriers; c) aged-matched premenopausal healthy donors (HDs). Complete aPL testing was performed and AMH levels were measured using enzyme-linked immunosorbent assay.
Results: Among the 69 patients included in the study, 22 were diagnosed with PAPS, 13 SAPS patients, and 14 patients were asymptomatic aPL carriers. No differences in AMH levels were observed among the 3 groups [mean AMH: PAPS 3,09 ng/ml±1,9 (range 1,02-7,1); SAPS 3,1 ng/ml±2,2 (range 1,1-7,6); aPL carriers 2,2 ng/ml±5,4 (range 1-6,3)] and between patients/carriers and HDs [mean AMH 2,82 ng/ml±2,9 (range 1-6,9)]. No correlation between the global APS score (GAPSS) and AMH levels were found (rho=0,31; p=0,073).
Conclusion: Despite the limitations of a cross-sectional study, as observed in women with APS, we confirm that ovarian reserve, assessed with AMH levels, is not reduced in premenopausal women with isolated aPL positivity. Moreover, when parsing out the aPL profile in terms of risk assessment, using the GAPSS, no impact on fertility was observed.
SUDDEN HEARING LOSS AS INITIAL MANIFESTATION IN PATIENTS WITH RHEUMATIC DISEASES: CASE SERIES
Marcela Patiño Arboleda1, Jorge Manuel Rueda Gutierrez1,2, and and Alvaro Arbelaez Cortes1,2. 1Universidad Libre de Cali, Departamento de Medicina Interna, Cali, Colombia, 2Centro Medico Imbanaco, Clínica de artritis y Reumatologia, Cali, Colombia.
Background: Sudden hearing loss is defined as a sensorineural hearing loss of more than 30 dB in at least three or more consecutive frequencies in less than 72 hours. Rheumatic diseases represent less than 1% of all the causes of sudden hearing loss, and in some cases, it may be the first manifestation of an immune-mediated systemic disorder.
Objective: We present 3 cases of patients with sudden hearing loss as the first manifestation of rheumatic disease, their diagnosis, management, and post-treatment results.
Materials and methods: We reviewed the medical records of these patients and updated a search of the topic.
Results: Three female patients, aged 50, 63 and 69, had sudden hearing loss as the first manifestation of Sjögren's disease in 2 cases and ANCA positive vasculitis in 1 case. Initially, they were evaluated by otolaryngology due to a history of sudden hearing loss associated with tinnitus, ear plugging and vertigo. Audiometry was performed and other causes of sudden sensorineural hearing loss were ruled out. Subsequently, they were referred to a rheumatologist who diagnosed through rheumatology laboratory exams, ophthalmologic evaluation and salivary gland biopsy the presence of an immune disorder which was associated as a causative factor of the auditory symptoms. In all 3 cases, management with systemic steroids was initiated, associated with immunosuppression with cyclophosphamide in the ANCA positive vasculitis patient, showing an improvement in the auditory compromise in all situations.
Conclusion: Despite being associated with a low percentage of immune-mediated rheumatic diseases, sudden hearing loss is an entity that should be considered as an initial manifestation. A timely diagnosis through simple tests such as otoscopy and acumetry performed in the primary health and emergency care network, followed by audiometry and adequate approach according to the etiological cause found, will allow the establishment of treatment effectively, thus improving the prognosis and quality of life of these patients. To our knowledge, we present the first 3 cases of an auditory manifestation as the first symptom of rheumatic diseases in Colombia.
THE EFFECT OF MELANOCORTIN PEPTIDES ON HUMAN PRIMARY OSTEOCLASTS
Vedia Can1, Clara De Pascale1, Ian Locke1, Paolo Grieco2, and Stephen Getting1. 1University of Westminster, London, United Kingdom, 2University of Naples Federico II, Naples, Italy.
Objectives: Osteoarthritis (OA) is estimated to affect more than 15% of the worldwide population and at present this degenerative joint disease requires novel treatment options. A role for the melanocortin peptides exerting anti-inflammatory effects has been shown, although the receptor subtype involved is unclear. This study aims to assess the osteoclast-protective and anti-inflammatory effects of the selective human MC1 receptor agonist BMS-470539 dihydrochloride, selective human MC3 receptor agonist PG-992 and the human MC1/3 receptor agonist [DTrp8]-γ-MSH on IL-1β activated human osteoclasts.
Methodology: Human primary osteoclasts isolated from human peripheral blood mononuclear cells were treated with the melanocortin peptides BMS-470539 dihydrochloride (10.0 μg/ml), PG-992 (3.0 μg/ml) and [DTrp8]-γ-MSH (3.0 μg/ml) alone or in the presence of IL-1β (1000 pg/ml) for 6h. Gene expression for hMC1, hMC3, Calcitonin, TRAP, Cathepsin-K, Integrin-β3 determined by RT-PCR. Cell viability was determined by MTT, pro-inflammatory mediator release (IL-6 and IL-8) and tissue destructive matrix metalloproteinase (MMP-1 and MMP-13) determined by ELISA. Data are expressed as Mean ±SD of n=4 samples repeated in triplicate. #p≤0.05 vs control or *p≤0.05 vs stimulus.
Results: RT-PCR showed hMC1, hMC3, Calcitonin, TRAP, Cathepsin-K and Integrin-β3 gene expression. Cell viability analysis showed IL-1β stimulation caused a maximal cell death of 23% (#p≤0.05), BMS-470539 dihydrochloride, PG-992 and [DTrp8]-γ-MSH inhibited cell death by 123%, 146% and 136% respectively (*p≤0.05). IL-1β stimulation caused a significant increase in IL-6, IL-8, MMP-1 and MMP-13 release. BMS-470539 dihydrochloride inhibited IL-6, IL-8, MMP-1 and MMP-13 release by 3%, 14%, 19% and 4% respectively (*p≤0.05). PG-992 inhibited IL-6, IL-8, MMP-1 and MMP-13 release by 50%, 44%, 69% and 80% respectively (*p≤0.05). [DTrp8]-γ-MSH inhibited IL-6, IL-8, MMP-1 and MMP-13 release by 36%, 39%, 45% and 28% respectively (*p≤0.05).
Conclusion: The selective hMC3 receptor agonist PG-992 exhibits enhanced modulation of IL-6, IL-8, MMP-1 and MMP-13 following IL-1β activation compared to the selective hMC1 receptor agonist BMS-470539 dihydrochloride. This suggests that targeting the hMC3 receptor sub-type for the development of treatment options for OA could be a possible avenue to explore.
ORGAN DAMAGE ACCRUAL IN PRIMARY ANTIPHOSPHOLIPID SYNDROME (PAPS): CORRELATION WITH HEALTH-RELATED QUALITY OF LIFE.
Luis J. Jara Quezada1, Gabriela Medina García1, Erik Antonio Cimé Aké1, Olga Lidia Vera Lastra1, and Miguel Angel Saavedra Salinas1. 1Hospital de Especialidades "Dr. Antonio Fraga Mouret", Centro Médico La Raza.IMSS, México City, México.
Background: The antiphospholipid syndrome (APS) affects young patients and the consequences of organic damage impact their health-related quality of life (HRQoL).
Objective: To determine the correlation of organ damage accrual with HRQoL in PAPS patients.
Material and Methods: Medical records review study design. In patients with PAPS, the Damage Index for Thrombotic APS (DIAPS) at 1, 5, 10, 15 and 20 years of follow-up was determined. Accrual of damage and HRQoL (measured by the SF-36) were assessed. Descriptive statistics and Spearman correlation test were employed.
Results: Sixty-seven patients were included, mean age 48.8 (±12.1) years; female gender (77.6%), deep venous thrombosis (71.6%) and the presence of the Lupus Anticoagulant (73.1%) predominated. During follow-up, the DIAPS medians were increased from 1 in the first year, to 2 at 5-10 years and to 3 at 15-20 years. Organ damage was found in 98.5%, increasing by 83.6% since diagnosis, with severe organ damage in almost 60%, with greater involvement in the neuropsychiatric, peripheral vascular and pulmonary domains. Regarding HRQoL, deterioration was found in the domains of general health (52.0, IQR 37.0-82.0), vitality (58.9±26.5), physical component summary (37.68, IQR -35.68-64.99) and mental component summary (53.78±14.08). DIAPS accrual was inversely correlated with all domains of SF-36, especially with body pain (rho=-0.503) and the physical component summary (rho= -0.475), p <0.001. The skin damage impacted negatively on the physical role (average range 21.32 vs. 36.49, p=0.017) and the physical component summary (average range 22.27 vs. 36.30, p=0.0 29).
Conclusions: Current organ damage accrual in patients with PAPS impairs the physical component of HRQoL. Thrombotic secondary prevention and control of cardiovascular risk factors are important to avoid further deterioration of their HRQoL.
Key words: Antiphospholipid syndrome, DIAPS, SF-36, neuropsychiatric damage, physical component summary, mental component summary.
ASYMPTOMATIC SEROLOGICAL ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS AND PREGNANCY: RISK OF MATERNAL-FETAL COMPLICATIONS
Luis J. Jara Quezada1, Miguel Ángel Saavedra Salinas1, Dafne Miranda Hérnandez1, Antonio Sánchez Gonzalez1, Reyna Elizabeth Sánchez Briones1, and Gabriela Medina1. 1Hospital de Especialidades "Dr. Antonio Fraga Mouret", Centro Médico La Raza.IMSS, México City, México.
Background and aim: The activity of systemic lupus erythematosus (SLE) during pregnancy is associated with an adverse maternal-fetal outcome. However, the role of asymptomatic serological activity has been poorly studied. Aim: To compare maternal-fetal complications in patients with SLE with clinical activity, serological (asymptomatic) activity and remission during pregnancy.
Methods: Longitudinal cohort (2009-2019) of pregnant women with SLE. Maternal-fetal outcomes were compared in 3 groups of patients classified according to disease activity: remission (without clinical, biochemical and / or serological manifestations), with activity (clinical and / or biochemical) and with serological activity (high levels of anti-DNA and / or hypocomplementemia in the absence of clinical manifestations).
Results: 392 pregnancies were included, 49.7% of the patients were in remission, 37.5% had clinical activity and 12.8% had serological activity. Patients with clinical activity and serological activity had a higher frequency of lupus nephritis (p = 0.02) as well as the use of prednisone (p <0.001), azathioprine (p <0.001) and low doses of aspirin (p <0.001) during pregnancy in comparison with those in remission. Newborns of patients with clinical activity and serological activity had a higher rate of neonatal adverse events compared to those in remission (Table)including prematurity, low birth weight and oligohydramnios. Likewise, patients with clinical or serological activity developed HELLP syndrome more frequently (p = 0.04).
Conclusion: Our study suggests that asymptomatic serological activity is associated with neonatal complications, similar to those SLE patients having clinical activity. Timely therapeutic interventions in these patients could improve the maternal-fetal outcome.
Key Words: Lupus pregnancy, maternal-fetal complications, serological activity
1. Saavedra MA, at al. Primigravida is associated with flare in women with systemic lupus erythematosus. Lupus. 2015 Feb;24(2):180-5.
• Borella E, et al. Predictors of maternal and fetal complications in SLE patients: a prospective study. Frontiers In Autoimmunity. Immunol Res (2014) 60:170-176.
EVALUATION OF AUTONOMIC NERVOUS SYSTEM THROUGHT HEART RATE VARIABILITY IN PATIENTS WITH PRIMARY ANTIPHOSPHOLIPID SYNDROME
Luis J. Jara Quezada1, Gabriela Medina García1, Luis Olmos Domínguez2, Milton Guevara Valdivia1, María del Pilar Cruz Domínguez1, and Miguel Angel Saavedra Salinas1. 1Hospital de Especialidades "Dr. Antonio Fraga Mouret", Centro Médico La Raza.IMSS, Mexico City, México, 2Hospital de Cardiología, Centro Médico Nacional Siglo XXI. IMSS., Mexico City, México.
Background: Heart rate variability (HRV) abnormalities identify autonomic nervous system disorders even in pre-clinical stage in rheumatic diseases. A systematic study of HRV in Primary (PAPS) has not been performed.
Objective: To determine HRV/electrocardiographic characteristics in PAPS.
Methods: Cross-sectional/comparative study. Patients with PAPS diagnosis (Sidney criteria) ≥ 18 years of age and a healthy control group matched by age, sex and BMI were included. Patients with NYHA Class 3 or 4, definitive pacemakers, severe valvulopathy, pregnancy, and anti-arrhythmics were excluded. Electrocardiogram and HRV in 24 hours by Holter were performed. Statistical analysis: Descriptive statistics, Student’s t test or Mann Whitney U test.
Results: Thirty-nine PAPS patients and 39 controls were included, age 49.4±13 years, disease course 14.4± 7.4 years, 71% had deep venous thrombosis, pulmonary embolism 35.8%, stroke 32.8 % and myocardial infarction 5.7%; dyslipidemia in 51%, arterial hypertension and obesity in 28.6%. All patients were on oral anticoagulants. In the PAPS group P wave amplitude was greater (0.127 mV ± 0.032 vs 0.111 mV ± 0.021, p = 0.032) and the minimum heart rate was lower (48 bpm ± 7 vs 52 bpm ± 7, p = 0.030). Parameters of HRV were higher in PAPS patients without statistical significance. There was no evidence of atrial fibrillation or ventricular tachycardia.
Conclusions: Significant difference in HRV was found in PAPS patients which suggest an increase in vagal tone, that prevents the development of malignant arrhythmias. P wave amplitude could be monitored as an indirect sign of pulmonary arterial hypertension and a possible predictor of mortality of pulmonary etiology.
Keywords: Holter, heart rate variability, antiphospholipid syndrome.
HIDDEN AUTO-ANTIBODIES IN PATIENTS UNDERGOING IMMUNOTHERAPY FOR CANCER
Tomas Urrego-Callejas1,2,4, Juan Felipe Soto-Restrepo1, Simón Sandoval-Álvarez1, Mateo Chvatal-Medina1, Rodolfo Gomez3, Gloria Vásquez1,2. 1Grupo Inmunología Celular e Inmunogenética. Universidad De Antioquía, Medellín, Colombia, 2Grupo de Reumatología, Universidad de Antioquía, Medellín, Colombia, 3Instituto de Cancerología. Clínica Las Americas-Auna, Medellín, Colombia, 4Grupo de Estudio de las Vasculitis Sistémicas, Universidad de Antioquía, Medellín, Colombia.
Introduction: Therapy with monoclonal antibodies against molecules such as CTLA-4 and PD-L1 are approved for the treatment and prevention of recurrence in multiple tumors; they represent a powerful treatment strategy. This therapy can induce a broad spectrum of adverse events, denominated immune-related adverse events (irAEs).
The presence of autoantibodies, specific or not, is not frequently evaluated. The most frequent finding is the presence of symptoms of autoimmunity without correlation with autoantibodies.
This study evaluated a group of patients under these therapies and the presence of clinical or serological autoimmunity.
Patients and methods: Twenty-three patients with a diagnosis of cancer undergoing immunotherapy were evaluated by a rheumatologist to establish the presence of clinical autoimmunity according to the American Society of Clinical Oncology (ASCO) guidelines.
A serum sample was obtained, and the presence of different autoantibodies was established.
Statistical analyses were performed with SPSS 23.0 (IBM SPSS 23.0, Chicago, IL, USA).
Results: Regarding clinical autoimmunity, the skin was the main organ involved. Three patients had vitiligo, one patient psoriasis, and five patients rash. Three of these patients had hair repigmentation. We also observed one patient with hypophysitis, and one patient with a sarcoid-like illness.
From a serological standpoint, we found 4 patients with anti-TPO, 5 patients with anti-parietal cell antibodies, and 6 patients with anti-smooth muscle antibodies. ANAs were present in 17 (74%) patients, 82% patients had at least one autoantibody, and 60% had at least 2 positive autoantibodies. 3 patients had ANA with titers of at least 1/160 and positive anti-Ro. We only observed one patient with anti CCP, and no patients had positive anti DNA, anti Sm, anti RNP or RF.
Conclusions: The induction of autoimmunity by checkpoint inhibitors is an interesting phenomenon, and hidden positive autoantibodies seem to be present in many in patients treated with such therapies. Whether or not this is a long-lasting phenomenon, or has any clinical repercussion is yet unknown. These data suggest that patients using checkpoint inhibitors may benefit from autoantibody screening to perform a more directed clinical follow up, to detect earlier any autoimmunity manifestation.
SUBCLINICAL ATHEROSCLEROSIS AND ITS RELATIONSHIP WITH INFLAMMATION BIOMARKERS IN PARAGUAYAN PATIENTS WITH RHEUMATOID ARTHRITIS
Johana Elizabeth Coronel Grunce1, Lourdes Román1, Vannia Valinotti1, Astrid Paats1, Susan Riquelme1, Alexis Pineda1, Gabriela Ávila1, Isabel Acosta Colman1, Maria Teresa Martinez2, Osmar Centurión1, and Sonia Cabrera Villalba1. 1Hospital De Clínicas, San Lorenzo, Paraguay, 2Laboratorio Curie, Asunción, Paraguay.
Objective: To determine the presence of inflammation biomarkers and their relationship with subclinical atherosclerosis measured by carotid ultrasound, and with the clinical characteristics in patients with established Rheumatoid Arthritis (RA)
Materials and Methods: Descriptive, cross sectional study, in a Paraguayan cohort of patients with RA meeting ACR/EULAR2010 criteria. This study had two phases: the first one, included a standardized questionnaire according to the variables included in the Cardiovascular Risk project (PINV15-0346), from the National Sciences and Technology Council (CONACYT), and physical examination; the second one included laboratory sample collection performed by a specialized laboratory for serum biomarkers measurement for cardiovascular risk prediction (i.e endothelin, alpha-TNF, E-selectin, homocysteine, apolipoprotein, fibrinogen, and high sensitivity-CRP levels) and carotid ultrasound evaluation by a trained specialist, to evaluate subclinical atherosclerosis. Subclinical atherosclerosis was defined as carotid intima-media thickness (CIMT) >0,9mm and/or presence of carotid plaques. All patients signed an informed consent. SPSS 23rd version was used for data analysis. Quantitative variables were presented as means and qualitative as frequencies. Chi square test was performed for the comparison between dichotomous variables and Students’ t for continuous variables;a p ≤ 0.05 was set for statistical significance.
Results: 100 patients were included, 87% were women, mean disease duration 130.9±102.64 months, 77% were RF positive, and 84.4% were ACPA positive, 43.4% had bone erosions, mean ESR-DAS28 was 3,42±1,1; 30% met remission criteria. 39% had extra-articular manifestations.
Elevated serum biomarkers were found: fibrinogen >400 mg/dL 88.2%, high sensitivity-CRP (hs-CRP) >5mg/dL 42.9%, endothelin >2 ng/mL 20%, alpha-TNF >15,6 pg/mL 13.1%, E-selectin >79,2 ng/mL 6%. 25.3% had CIMT >0,9 mm and mean CIMT was 0.68±0.25mm. 27.14% had carotid plaques. Patients with CIMT>0.9 mm had higher frequency of family history of arterial hypertension (p=0.006), longer mean disease duration (p=0.0007), hip circumference (p=0.014), blood pressure (SBP p=0.038, DBP p=0.027), HAQ levels (p=0,019) and hs-CRP levels (p=0.013); they also had lower mean height (p=0,04); while carotid plaques were related to higher homocysteine (p=0.026) and hs-CRP levels (p=0.024).
Conclusion: A considerable percentage of these RA patients had subclinical atherosclerosis. Patients with CIMT>0,9mm had a longer disease duration, higher HAQ levels, hip circumference, as well as higher BP. High levels of hs-CRP were more frequently related to the presence of subclinical atherosclerosis
PRIMARY SJÖGREN’S SYNDROME WITH PERIPHERAL POLYNEUROPATHY, HYPOKALEMIC PARALYSIS AND MITOCHONDRIAL POLYMYOSITIS AS THE INITIAL MANIFESTATIONS: A CASE REPORT AND LITERATURE REVIEW
Carolina García-Alfonso1,2, Julián Rondón-Carvajal1,2, and Sonia Millán Pérez1,2. 1Pontificia Universidad Javeriana, Bogotá, Colombia, 2Hospital Universitario San Ignacio, Bogotá, Colombia.
Objective: to describe the case of a pregnant patient who presented with acute weakness and severe hypokalemia, and developed a demyelinating polyneuropathy, hypokalemic paralysis, myositis with mitochondrial pathology as causes of weakness, being diagnosed with Sjögren’s syndrome; and to highlight the importance of identifying the extraglandular manifestations of this syndrome. Neurological manifestations of this entity are briefly discussed, including those secondary to metabolic disorders precipitated by autoimmune compromise.
Sjögren’s syndrome is a multisystemic entity of autoimmune nature, classically considered an exocrinopathy, given the high frequency of dry symptoms, as a result of polyglandular infiltration by autoreactive lymphocytes. However, less than 10% of these patients can initially present with severe extraglandular manifestations, resulting in worse long-term outcomes. The case of a previously healthy pregnant woman is presented, whose disease started with acute proximal weakness and myalgias, with severe hypokalemia and metabolic acidosis due to distal renal tubular acidosis. She had an elevated CK, persistent metabolic acidosis and multisystem failure requiring mechanical ventilation and extracorporeal membrane oxygenation. Hypokalemic paralysis was suspected due to partial improvement with potassium replacement. Nerve conduction studies showed demyelinating polyneuropathy. Because of the elevated CK and myalgias, a muscle biopsy was performed and reported myopathic changes with mitochondrial abnormalities and lipid accumulation, presence of red ragged fibers and HLA-I expression in some muscle fibers. Lipid metabolism disorders were considered within the differential diagnosis, as well as myopathies associated with autoimmunity such as polymyositis with mitochondrial pathology and inclusion body myositis. Acylcarnitine profile and lactate pyruvate were assessed and were normal and her family history was negative. Antinuclear antibody (ANA) test was positive in 1/2560 speckled pattern, and extractable nuclear antigen (ENA) test were positive for anti-SSA in 127.9. A minor salivary gland biopsy was performed showing mild chronic sialadenitis, Mason Chisholm grade 2, and a Schirmer test positive for bilateral dry eye, meeting ACR-EULAR 2017 criteria for primary Sjögren’s syndrome, and azathioprine combined with prednisone was started without full recovery.
Conclusion: Extraglandular manifestations of primary Sjögren’s syndrome (pSS) are being reported more frequently, even in the absence of dry symptoms, so the importance of investigating them in the anamnesis is highlighted. Their absence does not rule out the possibility of an extraglandular pSS. From the neurological point of view, when it is not possible to topographically locate a single lesion in the nervous system, the etiological search should be continued, since different extraglandular manifestations can occur simultaneously (myopathy, channelopathy and neuropathy).
PREVALENCE OF SPONDYLARTHRITIS IN PATIENTS WITH CROHN DISEASE AND ULCERATIVE COLITIS
Luciana Casalla1, Lucía Zárate1, María Julieta Gamba1, Paula Alejandra González1, María Carolina Conlon1, Renata Alina Spiazzi1, María Claudia Milano1, and María Nieves Capozzi1. 1Hospital Nacional A. Posadas, El Palomar, Argentina.
Introduction: Inflammatory bowel disease (IBD) associated spondylarthritis (SpA) has a clinically heterogeneous presentation, with peripheral joint and/or axial involvement. The frequency ranges from 10 to 40% of IBD cases. We have preliminary described, in 56 IBD patients followed up in our Institution, a prevalence of 21% of SpA when applying ASAS Classification Criteria for Axial and Peripheral SpA and modified New York (mNY) criteria for ankylosing spondylitis. In this communication we present the final data of that study.
Purpose: To evaluate the prevalence of SpA in patients with Ulcerative Colitis (UC) and Crohn's Disease (CD) according to ASAS and mNY criteria, and to describe clinical and radiological characteristics of these patients.
Methods: We conducted a cross-sectional observational study that included consecutive patients with UC or CD followed up by the Gastroenterology Section, and who were subsequently referred to the Rheumatology Section. Demographic data and characteristics of bowel condition were recorded. Rheumatologic data: history of SpA features, as well as clinical, laboratory and radiological data were collected. If required, joint ultrasound (US) and/or magnetic resonance imaging (MRI) were performed. IBD-SpA was defined in those patients who fulfilled peripheral ASAS, axial ASAS and/or mNY criteria.
Results: 120 IBD patients (58.3% women) were included: mean age 45±15 years, median IBD duration 54 (IQR 12-108) months; 73.3% patients had UC (83% in remission), and 26.7% CD (73% in remission). History of: arthralgias 45%, low back pain 37.5% (of which 15% was inflammatory), sacroiliac pain 4.2%, enthesis pain 17.5%, dactylitis 2.5%, psoriasis 4.2%, uveitis 0.8%, infection during the previous month 1.6%. Six percent of the patients had positive rheumatoid factor, and HLA B27 was determined in 31 patients (positive in one). Of all patients with IBD, 24 (20%) met SpA classification criteria: 20 peripheral ASAS, 3 axial ASAS and NYm, and 1 peripheral and axial ASAS. Of the 21 patients with peripheral SpA, 12 presented enthesitis, 8 arthritis, 1 dactylitis, 2 psoriasis and 1 history of uveitis.
Conclusion: In this study, the prevalence of SpA in IBD patients was 20%, with enthesitis and peripheral arthritis being the most frequently found manifestations. Considering these results, we highlight the role of interdisciplinary management of these patients for an early diagnosis of joint involvement.
PREVALENCE OF VITAMIN D DEFICIENCY/INSUFFICIENCY IN PATIENTS WITH RHEUMATIC DISEASES
Marcos Vázquez1, Astrid Paats1, Rodrigo Acosta1, Sonia Cabrera-Villalba1, Gabriela Ávila1, María Eugenia Acosta2, Ivalena de Guillén2, María Teresa Martínez de Filártiga3, and Isabel Acosta-Colmán1. 1Departamento de Reumatología, Hospital De Clínicas, Asunción, Paraguay, 2Instituto de Investigación de Ciencias de la Salud, San Lorenzo, Paraguay, 3Laboratorios Curie, Asunción, Paraguay.
Introduction: There are reports of vitamin D (VD) deficiency/insufficiency in many autoimmune rheumatic diseases and this has been inversely correlated with disease activity.
Objectives: To calculate the prevalence of vitamin D deficiency and insufficiency in 4 different rheumatic diseases and to determine if vitamin D levels differ between each group of patients and between rheumatic patients and healthy volunteers.
Methods: A total of 339 patients and 75 controls were included. Among the patients, 143 had a diagnosis of systemic lupus erythematosus (SLE), 197 of rheumatoid arthritis (RA), 48 of systemic sclerosis (SSc) and 51 of psoriasis. The plasma levels of 25-OH-VD were quantified by the Architect assay. VD deficiency was defined as plasma levels of 25-OH-VD <20ng/mL and insufficiency as 20 to 30ng/mL. One-way ANOVA test was used to compare mean plasma VD between the groups.
Results: In patients with rheumatic diseases, 29.8% (101/339) had VD deficiency and 43% (146/339) had VD insufficiency. Altogether, patients with VD levels below 30ng/mL reached 72.8% (247/339). Among healthy controls, 38.7% (29/75) had VD deficiency and 44% (33/75) had VD insufficiency. Mean VD levels in patients with SLE were 25.54 ± 9.19 ng/mL, in systemic sclerosis 25.31 ± 9.18 ng/mL, in rheumatoid arthritis 26.13 ± 8.81 ng/mL and in psoriasis 22.92 ± 7.29 ng/mL. In controls, mean VD levels was 24.4 ± 12.9 ng/mL. When comparing mean vitamin D levels between the 4 diseased groups and the control group, we found no significant differences (p= 0.156).
Conclusion: The prevalence of vitamin D deficiency and insufficiency is similar in SLE, RA, SSc and psoriasis and, at the same time, similar between patients with rheumatic diseases and healthy volunteers.
CLINICAL CHARACTERISTICS OF UVEITIS PATIENTS FROM AN AUTOINMUNE OCULAR DISEASE UNIT
Astrid Paats1, Vannia Valinotti1, Johana Coronel1, Susan Riquelme-Granada1, and Nelly Colmán1. 1Departamento de Reumatología, Hospital De Clínicas, Asunción, Paraguay.
Objective: To describe the clinical characteristics of patients diagnosed with uveitis and its association with systemic disease.
Methods: Medical records review, descriptive study. We included patients diagnosed with uveitis attending the Autoimmune Eye Disease Unit from January 2019 to December 2019. Qualitative variables were expressed as frequencies and percentages and quantitative variables as means and standard deviation.
Results: A total of 40 patients were included, 72.5% were women (26/40). Mean age at disease onset was 38 ± 17.2 years and the average diagnostic delay was 19.4 ± 46.8 months. The most frequent chief complaint was decrease in visual acuity, cited in 43.8% of the consults (25/57). Involvement was bilateral in 55% of cases (22/40). In order of decreasing frequency, diagnosis found were: Anterior uveitis in 47.5% (19/40), panuveitis in 35% (14/40), posterior uveitis in 10% (4/40) and intermediate uveitis in 7.5% (3/40). There was a recurrence (2 or more episodes of uveitis) in 65.7% (25/38) of patients and 58.8% (20/34) of them presented some sequelae. Prior to their first episode of uveitis, 12.5% (5/40) of patients had already been diagnosed with an autoimmune disease, the most common of which was spondyloarthropathy (3/5). Meanwhile, 33.3% (13/39) were diagnosed with a systemic disease from their first episode of uveitis. Regarding laboratory tests, 46.4% (13/28) of patients presented acute phase reactants, 13% (3/23) had positive serum antibodies and 41.6% (5/12) were HLA-B27 positive. Concerning treatment, 76.3% of patients required systemic corticosteroids (29/38) and 75% received at least one immunosuppressive drug (30/40). Out of this group, 30% needed a second immunosuppressive drug. Response to treatment was good in 63.6% of patients (21/33), partial in 18.1% (6/33), poor despite treatment in 6% (2/33) and poor due to lack of adherence in 12.1% (4/33).
Conclusion: In our study, there was a predominance of female, middle-aged patients with bilateral involvement. Anterior uveitis was the most frequent diagnosis. In one-third of the patients, the first episode of uveitis led to the diagnosis of a systemic disease. Most of our patients presented some type of sequela or local complication and required systemic treatment with corticosteroids and immunosuppressants.
RHEUMATOID ARTHRITIS: CLINICAL-THERAPEUTIC CHARACTERISTICS OF AN ECUADORIAN COHORT
Leonela Bastidas Granizo2,3, Joselyn Castillo Rodriguez1,2,3, and Andrés Zúñiga Vera3. 1Ministerio De Salud Pública-Centro De Salud La Victoria, Guayaquil, Ecuador, 2Hospital Teodoro Maldonado Carbo, Guayaquil, Ecuador, 3Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador.
Introduction: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that mainly involves synovial joints. In our population, it is considered one of the most prevalent inflammatory rheumatic diseases, affecting mainly women between 50-75 years.
Objective: To determine the clinical-therapeutic characteristics of an Ecuadorian cohort of RA patients with a follow-up of 3 years and assess the response to disease-modifying anti-rheumatic drugs.
Materials and methods: An observational, longitudinal medical records review study was carried out. A sample of 70 patients was randomly selected from the registers of the rheumatology outpatient service of Teodoro Maldonado Carbo hospital of Guayaquil. From the population of patients diagnosed with RA in 2016, a sample of 35 patients was selected and followed up for 3 years. A control group, with 35 patients who already had a diagnosis of RA prior to the first consultation in 2016, was also followed up.
Results: 70 patients were included in our study; 68 were female (97.1%) and the average age was 56 years. 54,28% of the patients did not present extra articular manifestations. 95% used methotrexate and biologics were used in 37.14%, being rituximab the most common. The main reason for discontinuation of treatment was the presence of adverse effects for methotrexate, sulfasalazine and chloroquine; as for rituximab and etanercept, lavck of efficacy was described as the cause of discontinuation. Clinical response to methotrexate was evaluated by changes in CDAI every 4 months. The baseline CDAI was lower for the control group (10,48 vs 20,60), and at 12 months of follow up, the mean CDAI for both groups was close. The efficacy of methotrexate was determined by a decreased in the number of patients with high to moderate activity of the disease (33,3%) and an increased number of patients in low activity and remission (66,6%) at 36 months of follow up. The combined pharmacological survival of methotrexate and prednisone was 32 months as the Kaplan Meier curve shows.
Conclusions: The most prevalent gender in RA was female. Most patients did not present extra articular manifestations. The most commonly used drug was methotrexate. The presence of side effects and lack of efficacy were the main reasons for its discontinuation. Clinical response and methotrexate efficacy were adequate in both groups of patients.
STUDY OF THE NEUTROPHIL/LYMPHOCYTE RATIO IN CHILEAN PATIENTS WITH RHEUMATOID ARTHRITIS DURING BIOLOGIC DISEASE-MODIFYING ANTI RHEUMATIC DRUG
Irene Castro Esparza1,2, Camila Ramírez2, QF Belén Cáceres Guerrero3, BQ Alejandra Flores Flores3, Estefania Nova-Lamperti3, and Liliana Lamperti Fernández3,4. 1Departamento de Medicina Interna, Facultad de Medicina, Universidad de Concepción, Concepción, Chile, 2Hospital Guillermo Grant Benavente, Concepción, Chile, 3Laboratorio de Inmunología Molecular &Traslacional, Departamento de Bioquímica Clínica e Inmunología, Facultad de Farmacia, Universidad de Concepción, Concepción, Chile, 4Laboratorio Clínico PreveGen, Concepción, Chile.
Introduction: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the synovial membrane and joints. The diagnosis of this pathology is currently based on the clinic and immuno-hematological laboratory tests. In the clinic, the activity of the disease is determined with the DAS28 score, which is used to determine the efficacy of conventional and biologic disease-modifying antirheumatic drug (DMARD). In Chilean RA patients, DAS28-VHS is measured 3- and 6-months after therapy with biologic DMARDs, however this score does not include inflammatory parameters associated to the immune system. The neutrophil/lymphocyte ratio (NLR) has been described as a novel parameter of inflammation associated with an increase innate response, with a predominance of neutrophils, as well as a reduced presence of lymphocytes. The NLR in RA has been shown to be an early and cost-effective inflammatory parameter in Japan, South Korea, India and Australia; however it is unknown if Chilean patients exhibit similar associations with disease activity.
Aim: The aim of this research was to evaluate the NLR in Chilean RA patients treated with biologic DMARDs.
Methodology: NLR and clinical parameters were measured in 91 RA patients from the Rheumatology Clinic from Guillermo Grant Benavente´s Hospital, classified accordingly to the 2014 EULAR criteria, before and 3- and 6-months after biological therapy, including Abatacept (n=37), Adalimumab (n=32) and Etanercept (n=22).
Results: Our overall data showed that RA patients with effective treatment exhibited an NLR of 2.48 (p<0.05) before therapy, NLR of 1.77 3-months and NLR of 1.17 6-months post-therapy. Refractory RA patients showed no NLR reduction post-treatment. When the effective therapies were evaluated separately, we observed that only Adalimumab treated patients showed a significant reduction in the NLR at both time points, whereas Abatacept and Etanercept showed no significant difference. When all the data, including different time points, were analyzed accordingly to the DAS28-VSH score, the NLR was 2.82±2.95 in patients with high activity, 2.17±1.86in patients with moderate activity, 1.68±0.62in patients with low activity and 1.65±0.71 inpatient in remission, showing a positive correlation between NLR and DAS28 (r=0.3408, p<0.0001).
Conclusion: In summary, our data revealed that the NLR was higher in RA patients with high disease activity compared to moderate and low activity, and this parameter correlated positively with DAS28.
PREGNANCY OUTCOMES IN WOMEN WITH RHEUMATIC DISEASES IN A SINGLE CENTER FROM GUATEMALA
Valeria Rodríguez Cárcamo1, Nilmo Chávez1, Silvia Rivera1, Estuardo Anzueto1, Gilbert Martínez1, and Marlon Arita1. 1Instituto Guatemalteco De Seguridad Social, Guatemala, Guatemala.
Background and Objective: Rheumatic diseases occur more frequently in women in the reproductive stage, so pregnancy is potentially frequent. Pregnancy requires endocrine and immune interactions, which can affect the clinical course of autoimmune disease and in turn influence the maternal and fetal outcomes, so they are considered high-risk pregnancies. The objective of this study was to determine the epidemiological behavior of patients with rheumatic diseases in the gestational stage and outcome.
Methods: Observational study in 20 patients with rheumatic disease and pregnancy, seen in the Rheumatology unit of the Guatemalan Social Security Institute (IGSS), from June 2018 to December 2019. Demographic variables were recorded, disease duration, clinical and laboratory manifestations, pregnancy, abortions, caesarean sections, living children, fetal deaths and maternal complications, type of delivery, birth weight, immunosuppressive treatment, steroid dose at the time of conception. Relative frequencies and percentages were used for the statistical analysis.
Results: 20 patients were included; three of the pregnancies are still in progress; in the other 17 88.2% were born alive and healthy, 3 patients presented maternal complications (17.6%): preeclampsia (2) and gestational hypertension (1). Just a fetal loss with an abortion. Preterm deliveries occurred in 6 (37.5%) and low birth weight in 5 (31.2%). No maternal deaths were recorded.
Conclusion: More than 88% of women with rheumatic diseases completed their pregnancies and had healthy births. The predominant maternal-fetal complications were preterm births and low birth weight. The present study shows the percentage similar to other studies, however, it is necessary to implement preconception counseling measures in Rheumatology units, to ensure a good result and avoid preventable complications over time.
URIC ACID DOES NOT INDEPENDENTLY PREDICT MORALITY IN TAIWANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS
Chin-Hsiao Tseng1. 1National Taiwan University Hospital, Taipei, Taiwan.
Objectives: To investigate whether uric acid levels could be predictive for all-cause mortality, cancer mortality and non-cancer mortality in Taiwanese patients with type 2 diabetes mellitus.
Material and Methods: This is a longitudinal follow-up study that enrolled a cohort of 1395 Taiwanese patients with type 2 diabetes mellitus who lived in the northern region of Taiwan. Baseline uric acid level was measured and potential confounders included the following variables at baseline were obtained: age, sex, diabetes duration, body mass index, fasting glucose, hemoglobin A1c, albumin-to-creatinine ratio (natural log transformed), total cholesterol, triglyceride (natural log transformed), systolic blood pressure, diastolic blood pressure, smoking, insulin use, cardiovascular disease, hypertension and dyslipidemia. Mortality was verified by matching the national death registration database until the end of 2014. Cox regression was used to estimate the unadjusted and multivariate-adjusted hazard ratios.
Results: At the beginning of follow-up, there were 670 male and 725 female patients. The mean age was 63.1 (standard deviation: 11.3) years and the mean diabetes duration was 11.0 (standard deviation: 7.9) years. After a median follow-up of 13.9 years, 267 patients died; among them, 63 were ascribed to cancer deaths and in 204 were ascribed to non-cancer deaths. In the unadjusted models, uric acid was predictive of all-cause mortality (hazard ratio: 1.079, 95% confidence interval: 1.021-1.140) and non-cancer mortality (hazard ratio: 1.109, 95% confidence interval: 1.043-1.178) but not of cancer mortality. In the multivariate-adjusted model, uric acid had a neutral effect on all-cause mortality, cancer mortality or non-cancer mortality in either the unadjusted models or the multivariate-adjusted models.
Conclusions: Although uric acid is predictive of all-cause mortality and non-cancer mortality in the unadjusted models, it is not an independent predictor for either all-cause mortality, cancer mortality or non-cancer mortality after adjusting of potential confounders in Taiwanese patients with type 2 diabetes mellitus.
VENOUS THROMBOEMBOLIC DISEASE IN ANCA ASSOCIATED VASCULITIS PATIENTS
Lucila Garcia1, Claudia Pena1, Santiago Ruta1, Mariana Pera1, Alan Raschia1, Maximo Cosentino1, Fernando Arizpe1, Florencia Savy1, and Mercedes Garcia1. 1Hospital Interzonal General de Agudos San Martín, La Plata, Argentina.
Objective: To evaluate the frequency of venous thromboembolic disease (VTD) and associated factors in AVV patients.
Material and Methods: Medical records review, observational and analytical study. Patients with AVV (ACR 1990 Classification/ Chapel Hill Consensus Conference 2012) were included.
Patients with Deep Vein Thrombosis (DVT) and/or Pulmonary Thromboembolism (PTE) confirmed by imaging were included.
Demographic data, traditional cardiovascular risk factors and other prothrombotic factors were examined.
Patients with and without thrombotic events were compared with Student’s t Mann Whitney tests for continuous data and with Chi square or Exact Fisher tests for categoric variables. The bivariate analysis was performed to evaluate variables and their effect on patients with and without DVT/ PTE. For each parameter significantly associated in the bivariate analysis, the binary logistic regression model was applied.
Results: Eighty-seven patients with AVV were included. The frequency of thrombosis was 13.7% (CI 95%: 7-22). Table 1 shows patients characteristics.
In bivariate and multivariate analysis, previous immobilization was the unique factor associated with thrombotic events. Sixty-six percent of the patients with DVT/PTE were immobilized compared with 13% of the patients that had not thrombosis (p < 0.0001). In Logistic Regression analysis, OR immobilization for DVT/ PTE was 35.4 (CI 95% de 2.5-491).
Conclusions: The frequency of DVT/PTE in VAA patients was 13.7% and only previous immobilization was associated with thrombotic events.
COMPARISON OF EFFICACY BETWEEN THE ANAM INSTRUMENT AND THE WECHSLER INTELLIGENCE SCALES IN NEUROPSYCHIATRIC LUPUS
Jaqueline Amorim1, Simone Thiemi Kishimoto1, Cibele Elorza1, Paula Teixeira1, Lilian Costallat1, Simone Appenzeller1. 1Unicamp, Campinas, Brazil.
Objectives: Among the neuropsychiatric manifestations of Systemic Lupus Erythematosus, cognitive losses are frequent. The translation and validation of Ped-Anam (Automated Pediatric Neuropsychological Assessment) for Children or Anam (Automated Neuropsychological Measurement) for adults allows the screening of these functions. Therefore, the objective of this study was to compare the results of this automated battery with the Wechsler Intelligence Scales.
Methods: This is a cross-sectional quantitative study. PedAnam has been translated into Portuguese following the "Guidelines for the process of transcultural adaptation of self-report measures". The battery is constituted of 10 subtests that were related according to area, content and evaluation to the subtests of the Wechsler scales. Wechsler Intelligence Scale for Children (WISC) and Wechsler Adult Intelligence Scale (WAIS) were applied to children. After the application, the results were compared.
Results: 32 adults with a mean of 27 years of SD ± 11.3 and 12 children with an average of 12 years of SD ± 3.8 were included. 31 women and 13 men. The subjects responded to the two tests on different days due to the time of the applications. The results were analyzed using the Spearman test, considering the closer to 1 the greater the positive correlation and the closer to -1 the negative correlation. The Code Substitution-Learning sub-test is more similar when compared to the digit span (r = 0.958), both assess the speed of perceptual comparison. Next, Mathematical Processing with Arithmetic Subtest (r = 0.640), measurement of basic computational skills, concentration and mathematical aspects. Sub-tests related to memory can be observed moderate correlation (r = 0.413). While the Matching Grids and Simple Reaction Time subtests are moderately related Digit Symbol Coding. Finally, subtests related to executive functions Spatial Processing with Block Design (r = 0.286).
Conclusions: The Wechsler scales are longer when compared to computerized ANAM batteries. The computerized battery presented correspondence with the content and the result varied from reasonable to excellent. It is a good battery for tracking cognitive demands, exploring different areas of cognition. Further research is needed to confirm the excellent accuracy in identifying cognitive impairment as well as its usefulness in detecting clinically relevant changes in cognition over time.
EVALUATION OF AGREEMENT BETWEEN HISTOLOGICAL CLASS IN KIDNEY BIOPSY AND CLINICAL INFERENCE OF LUPUS NEPHRITIS BASED ON CLINICAL AND LABORATORY DATA
Antonio Silaide De Araujo Júnior1, Alexandre Wagner Silva De Souza1, Martin Fábio Jennings Simões1, Gianna Mastroianni Kirsztajn2, Ricardo De Castro Cintra Sesso2, Emília Inoue Sato1, and Edgard Torres Dos Reis Neto1. 1Rheumatology Division. Universidade Federal De São Paulo, São Paulo, Brazil, 2Nephrology Division. Universidade Federal De São Paulo, São Paulo, Brazil.
Institution:1Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo. 2Nephrology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo.
Introduction: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. Lupus nephritis (LN) is one of the main causes of morbidity and mortality in SLE patients. Kidney biopsy is considered the gold standard for its diagnosis and is useful for guiding therapy.
Objectives: To evaluate the correlation of histological class inference based only on clinical manifestations and laboratory tests between rheumatologists and nephrologists and the kidney biopsy in SLE patients with LN.
Methods: A medical records review study based on analysis of medical records of 80 SLE patients in whom a kidney biopsy was performed between 2010 and 2017. Two rheumatologists and two nephrologists (one of each recognized and experienced specialists in the treatment of SLE and the others with general practice in their respective specialty) received clinical and laboratory data in the form of case summaries, then answered questions about which histological class was expected in the kidney biopsy and which treatment they would indicate. Statistical analysis: To assess the agreement between appraisers and the kidney biopsy and treatment, kappa agreement coefficient was used. p<0.05 was considered significant.
Results: the mean age of patients was 33±10.3 years, the mean disease duration was 11.5±6.7 years and SLEDAI was 16,38±7,75. The mean serum creatinine and 24-hour proteinuria were, respectively, 1.85±1.88mg/dL and 4.4±3.69g. The proliferative histological classes (III or IV) (61.3%) and treatment with methylprednisolone and cyclophosphamide (62.5%) were the most observed in the medical records. The level of agreement between the evaluators and the kidney biopsy was considered weak (Kappa 0.364±0.029; p<0.001);the rheumatologist with experience in the treatment of SLE presented the best results (Kappa 0.383±0.067; p<0.001), although it was still weak. The best agreement occurred between the two nephrologists (Kappa 0.512±0.072; p<0.001). Regarding treatment, we also found a weak level of agreement (Kappa 0.265±0.037; p<0.001), with the best agreement found between cyclophosphamide and mycophenolate as induction therapy (Kappa 0.311±0.046; p<0.001), although it was still weak.
Conclusions: both rheumatologists and nephrologists with experience in the treatment of SLE, as well as those in general practice in their respective specialties, presented a weak correlation index between the inferred histological class and the kidney biopsy findings, as well, between the proposed treatment and the treatment that was indicated based on kidney biopsy at the rheumatology outpatient clinic. Thus, kidney biopsy is a procedure that adds highly relevant information to the diagnosis and treatment of patients with LN.
Keywords: Systemic lupus erythematosus, Lupus nephritis, Biopsy, Treatment
CLINICAL AND LABORATORY MANIFESTATIONS AS PREDICTORS OF KIDNEY BIOPSY FINDINGS IN PATIENTS WITH LUPUS NEPHRITIS
Antônio Silaide De Araújo Júnior1, Alexandre Wagner Silva De Souza1, Martin Fábio Jennings Simões1, Gianna Mastroianni Kirsztajn2, Ricardo De Castro Cintra Sesso2, Emília Inoue Sato1, and Edgard Torres dos Reis-Neto1. 1Rheumatology Division, Department of Medicine, Universidade Federal de São Paulo/Unifesp. 2Nephrology Division, Department of Medicine, Universidade Federal de São Paulo / Unifesp, Brazil.
Introduction: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease. Lupus nephritis (LN) is one of the main causes of morbidity and mortality in SLE patients. Kidney biopsy is the gold standard for its diagnosis. Clinical and laboratory manifestations may be related to some subtypes of histopathological classes and some patients may have a contraindication for a kidney biopsy.
Objectives: To evaluate the correlation between clinical and laboratory data and histological classes of LN and to develop an instrument that can assist in the identification of the histological class in LN.
Methodology: A medical records review study based on analysis of medical records of 80 SLE patients undergoing kidney biopsy between 2010 and 2017 was performed. Clinical and laboratory data (age, race, hypertension, edema, serum creatinine, urinary sediment, 24-hour proteinuria, anti-dsDNA antibody and serum complement) were obtained at the time of kidney biopsy and were correlated with LN histological class found on the biopsy. Statistical analysis: The means were compared by ANOVA. A decision tree was constructed via CHAID (Chi Square Interaction Detector) and univariate and multivariate logistic regression were performed. p<0.05 was considered significant.
Results: The average age was 33±10.3 years, the mean disease duration was 11.5±6.7 years and SLEDAI was 16,38±7,75. The mean serum creatinine and 24-hour proteinuria were, respectively, 1.85±1.88mg/dL and 4.4±3.69g. The proliferative histological classes (III or IV) were the most common on kidney biopsy (61.3%), followed by classes V (25%), I or II (7.5%) and VI (2.5%). Patients with class II presented less hypertension and those with class VI presented lower levels of proteinuria, higher creatinine, absence of anti-dsDNA antibodies and complement consumption. Patients with altered urinary sediment, hypertension and serum creatinine>0.84mg/dL presented 96.4% of chance to belonging to class III or IV. Analyzing the laboratory variables as predictors of proliferative histological class (III or IV), patients with abnormal urinary sediment had 13.96 times higher risk and those with positive anti-dsDNA antibodies presented 4.96 times higher risk of having class III or IV (p<0.001). Our instrument presents a sensitivity of 87.8% and an specificity of 80% (AUC 0,890; CI 95% 0.81-0.97; p<0.001) using abnormal urinary sediment, anti-dsDNA antibodies and serum creatinine as variables.
Conclusions: Patients with classes III or IV had more frequently hypertension, altered urinary sediment, higher creatinine levels, positive anti-dsDNA antibody, complement consumption and nephrotic pattern proteinuria. When the kidney biopsy is unavailable or contraindicated, analytical tools based on clinical and laboratory predictors may be helpful.
Keywords: Systemic lupus erythematosus, Lupus nephritis, Biopsy, Treatment.
IMMUNE CHECKPOINT INHIBITOR THERAPY AND AUTOIMMUNE MANIFESTATIONS. A SINGLE BRAZILIAN CENTER EXPERIENCE.
Rafael A. Schmerling, Antonio C. Buzaid, Carolina K. Haddad, Fabio A.B. Schutz, Fabio R. Kater, Juliana Pimenta, William N. William, Camila Lopes, Daphne Bromberg, Ana C. Oliveira, Ana C.S. Galdino, and Morton Scheinberg. Oncology and Autoimmune Disease Center Hospital Beneficiencia Portuguesa São Paulo, Brazil.
Objectives: To evaluate by review of medical records the prevalence and type of autoimmune events in patients receiving immune check point inhibitor(ICIs) in the Complex Beneficiencia Portuguesa, a tertiary hospital in the city of S. Paulo, Brazil.
Methods: A single center study in patients receiving ICIs on the period of 2012-2019 (July). Time of appearance, tumor response, preexisting autoimmune disease, treatment outcome of the autoimmune manifestations and clinical characteristics were assessed.
Results: Five hundred and fifty seven patients received ICIs distributed among Nivolumab (219), Pembrolizumab (123) Aterolizumab (54), Ipilumab (141), Durvalumab (5), Avelumab (2), and combination of ICIs (67). Autoimmune clinical presentations were detected in 22% of the patients in order of magnitude in the systems, endocrine, cutaneous, musculoskeletal, intestinal and neurological. Thirty-one had preexisting autoimmune disease and sixteen required treatment with steroids or hormone replacement. In eight patients the ICIs were discontinued due to the persistent presence of autoimmune manifestations in spite of treatment. The mean time of appearance was 5.5 months.
A correlation between tumor regression and the appearance of autoimmune signs and symptoms was observed. Malignant melanoma accounted for 25% of the patient population receiving ICIs during this period and autoimmunity was detected in 60% of them.
Conclusions: This is one of the largest single center experience in Latin America confirming the association of autoimmune diseases with ICIs therapy in cancer patients. Discontinuation of ICIs due to autoimmunity was a rare event.
VITAMIN D TREATMENT ATTENUATED MUSCLE ATROPHY IN PRISTANE-INDUCED LUPUS MODEL
Silvia Guaresi1,3, Manuela dos Santos1,2,3, Jordana Miranda de Souza Silva1,2,3, Eduarda Correa Freitas1,3, Amanda Busatto1,3, Rafaela Cavalheiro do Espirito Santo1,3, Odirlei Monticielo1,3, and Ricardo Machado Xavier1,3. 1Laboratório de Doenças Autoimunes, Divisão de Reumatologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 2Programa de Pós-Graduação em Medicina: Ciências Médicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil, 3Divisão de Reumatologia, Departamento de Medicina Interna, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brasil.
Objective: To evaluate variation in skeletal muscle after the use of vitamin D supplementation using the pristane-induced lupus model.
Methods: Twenty-eight female Balb/c mice, 8-12 weeks-old, were randomly divided into three groups: healthy control (CO), pristine-induced lupus (PIL), PIL treated with vitamin D every two days (VD). At days 0, 60, 120 and 180 physical function was evaluated by fatigue, muscle strength and mobility tests. Tibialis anterior and gastrocnemius muscles were collected for myofiber area evaluation and protein expression of muscle regeneration, synthesis (MyoD, myostatin) and degradation (LC3) markers by Western blot.
Results: A significant reduction in myofiber area was observed in the PIL group compared to the CO group (p < 0.05) and VD group (p < 0.05). LC3 expression was significantly higher in the PIL group than in the CO (p < 0.05) and VD (p < 0.05) groups. MyoD expression was higher in the PIL group than in the VD group (p < 0.05). In addition, VD group presented a higher myostatin expression compared to the PIL group (p < 0.05). During the physical performance, we found increase of muscle strength between days 60 and 120 on VD group.
Conclusion: Pristane-induced lupus model causes muscle atrophy and it may be due to increased autophagy, which is attenuated by vitamin D supplementation. This is the first study to evaluate the effect of vitamin D on muscle atrophy mechanisms.
SARC-F QUESTIONNAIRE AND ITS ASSOCIATION WITH COMORBIDITIES, PHYSICAL DISABILITY AND LOWER ALBUMIN LEVELS IN SYSTEMIC SCLEROSIS PATIENTS
Senhor Leonardo Peterson dos Santos1, Rafaela C. Espírito Santo1,2, Vanessa Hax2, Rafael Chakr1,2, and Ricardo M. Xavier1,2. 1Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brasil, 2Serviço de Reumatologia do Hospital de Clínicas de Porto Alegre, Porto Alegre, Brasil.
Objective: To assess the association between the SARC-F questionnaire with clinical features in patients with systemic sclerosis (SSc). SARC-F is a simple questionnaire validated to screen for the presence of sarcopenia.
Materials and methods: Ninety-four patients diagnosed with systemic sclerosis were recruited and evaluated. Sarcopenia was assessed by the SARC-F questionnaire. Clinical features as disease duration time, comorbidities, body mass index (BMI), functional capacity by the Health Assessment Questionnaire (HAQ), inflammatory markers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), creatine phosphokinase (CPK), hemoglobin, creatinine and albumin) were obtained from the medical records. Frequency analysis, descriptive analysis and Pearson’s correlations were performed. Statistical significance was considered as p<0,05.
Results: Of the 94 patients examined, most were women (87/94;92.6%) with mean age of 60.5±10.3 years, median disease duration time of 11.2 (7.5-18.9 years) and median number of comorbidities of 1.00 (1.00-2.00). The mean BMI was 25.9±4.7 Kg/m2. Twenty-one of the patients were classified as active or passive smokers, thirty-five said they were former smokers and thirty-eight never smoked. Sixty-nine (80, 2%) out of the ninety-four patients in the study had at least one type of comorbidity (mean 1, 44±1, 04). Eighty-three patients (88.3%) showed a SARC-F score without signs suggestive of sarcopenia (0-5) whereas in eleven patients (11.7%) changes suggestive to sarcopenia were found (6-10). In HAQ, fifty-seven (60.6%) patients had mild discapacity, thirty-five (37.2%) had moderate discapacity, and two patients (2.2%) had severe discapacity. Higher SARC-F scores were associated with greater number of comorbidities (r=0.2; p=0.027), higher physical disability by HAQ (r= 0.5; p=0.000) and lower albumin levels (r= -0.3; p= 0.048). On the other hand, SARC-F was not associated with time of diagnosis, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), creatine Phosphokinase (CPK), hemoglobin, hematocrit and creatinine.
Conclusion: SARC-F scores were associated with comorbidities, physical disability and lower albumin levels in systemic sclerosis patients. Considering that comorbidities, physical disability and the albumin deficit enhances the patient's muscle loss, SARC-F appears to be a good tool to screen for sarcopenia in systemic sclerosis patients. Longitudinal studies are necessary to validate the SARC-F questionnaire in this population.
MORTALITY IN HOSPITALIZED ADULT PATIENTS WITH PRIMARY SYSTEMIC VASCULITIS
Florencia Savy1, Claudia Pena1, Santiago Ruta1, Victoria Martire1, Lucila Garcia1, Sofia Velloso1, Fernando Arizpe1, Alan Raschia1, Cosentino Maximo1, Mercedes Garcia1, Adriana Testi1, and Carolina Costi1. 1Hospital Interzonal General de Agudos San Martín, La Plata, Argentina.
Objective: To estimate the frequency of mortality in patients diagnosed with primary vasculitis who have required a hospitalization.
To evaluate predictive factors associated with mortality
Materials and Methods: For this medical records review and observational study, we included patients aged ≥16 years with a primary vasculitis diagnosis (1990 ACR Criteria 1990 or 2012 Chapel Hill Consensus) that required a hospitalization between July 2000 and August 2019 in a tertiary care center.
Results: 132 hospitalizations were recorded for 82 patients. From those, 65.9% were women, with an average age of 48.6 years at the time of hospitalization (SD: 16.2) and an average of 17.3 days of hospitalization (SD: 16.3). Among the vasculitis that required hospitalization, we found Granulomatosis with Polyangiitis 40.9%, Microscopic Polyangiitis 25.0%, undifferentiated Vasculitis associated with ANCA 8.3%, Takayasu Arteritis 9.0%, IgA Vasculitis 3.7%, Behcet's Disease 3.0%, Polyarteritis Nodosa 2.2% and Cryoglobulinemic Vasculitis 0.7%.
Initial diagnosis of vasculitis was made during hospitalization in 31 patients (23.4%).
The most frequent cause of hospitalization was disease activity (80.3%), of which 25.7% was at the pulmonary level, 20.4 % at the renal level and 7.5% at the nervous system level. The activity score calculated by BVASv3 media was 11.06 (SD 6.89).
Infections represented the second cause of hospitalization (34.0%), including respiratory 22.7%, urinary tract 5.3% and gastrointestinal 3.0% infections
7.58% of the hospitalizations were admitted to the coronary unit and 15.9% to the intensive critical care.
A total of 14 deaths (10.6%) were recorded.
In the bivariate analysis, mortality during hospitalization was associated with age (58.1 years, SD: 15.3 in patients who died vs. 47.7 years, SD 16 in those who survived, p = 0.03), with male sex (64.2% of those who died were men vs. 35.7% of women, p = 0.017), days of hospitalization (average days of hospitalization in patients who died of 27.4, SD: 11.9 vs. 16.1, SD: 14.4 in patients who survived) and the presence of respiratory infections (57.1% in patients who died vs 18.6% in those who survived, p = 0.0012).
In the multivariate logistic regression analysis, the only variable that was associated with mortality during hospitalization was the presence of respiratory infections with an OR: 8.75 (95% CI: 1.9-39.9).
Conclusion: In our center, ANCA-associated vasculitis was the predominant type of primary vasculitis that required hospitalization. Mortality was associated with male sex and respiratory infections. We emphasize the importance of detection and opportune treatment of respiratory infections.
NEONATAL LUPUS: FREQUENCY AND LONG-TERM MONITORING OF CASES IN A 3RD LEVEL CENTER
Maria Sofia Velloso1. 1H.i.g.a. San Martín. La Plata, La Plata, Argentina.
Introduction: Neonatal Lupus (LN) is a rare syndrome that affects 2% of the product of pregnancy in women with autoantibodies against SSA / Ro and SSB / La (anti-SSA / SSB) antigens.
Objective: To describe the frequency of NL in an Argentinian population and to describe maternal, fetus or newborn clinical features and to evaluate the long-term outcome of detected cases.
Patients and Methods: Cross sectional, observational, medical records review study in a 3rd level referral center from 1990 to July 2019. We included female patients that had at least one pregnancy. Demographic data, clinical manifestations, immunological profile, pregnancy, fetal and treatment data were collected.
Results: 202 pregnancies were evaluated, 58 of them had positive SSA / Ro and/or SSB / La Antibodies. Neonatal Lupus occurred in 5.4% (11/202), 45.4% (5/11) presented a rheumatic disease and only 2 of the 11 patients still remain asymptomatic. Neonatal lupus diagnosis was performed in 45.5% (5/11) during pregnancy and in 54.5% (6/11) in the postnatal period. Cardiac involvement was the most frequent (63.3% (7/11)), two of them required pacemaker placement, following by nine cases of cytopenias and 2 cases of cutaneous manifestations. Mortality was present in 27.3% (3/11).
Conclusions: In our experience we found that cardiac involvement is the most frequent manifestation and has a high mortality. Clinical manifestations as cytopenias or cutaneous involvement seem to be mild and transient with complete resolution within the first year of life. We consider that the high prevalence of this syndrome in this cohort of patients, can be attributed to the characteristic of our center (high-risk pregnancy derivation center).
USEFULNESS OF ULTRASOUND-GUIDED INTRA-ARTICULAR CARPAL INJECTIONS IN RHEUMATOID ARTHRITIS PATIENTS.
Juan Arguello1, L Santiago, C Troitiño, H Najera, and M Mamani. 1Hospital Rivadavia, CABA, Argentina.
Abstract: Joint echography is a noninvasive, economical and accessible image method. It presents a higher sensitivity for synovitis detection than the physical exam. It has been widely used as a diagnostic method and to guide intra-articular injections in a variety of rheumatological pathologies. It has also been demonstrated to increase the procedure´s effectiveness in some anatomic areas of the knee.
Until now, there has not been any published studies that have evaluated the application of this guided procedure in the carpal joint; this is the reason that the present work was done.
OBJECTIVES: To determine the benefit of ultrasound-guided intra-carpal injection in Rheumatoid Arthritis (RA) patients.
DESIGN: Semi- experimental, analytical, longitudinal study.
METHODS: Patients with RA according to ACR EULAR 2010 or ACR 1987 criteria being followed at the Rheumatology Service of Rivadavia´s Hospital from 2/6/2018 to 31/12/2019 were included. Betamethasone dipropionate 4 mg and betamethasone disodium phosphate 4 mg was used for intra-articular injection. Gray Scale and Power Doppler techniques were used.
All patients that needed this treatment had a baseline physical examination and an echography. (1st evaluation). Only patients with echographycally-confirmed carpal synovitis (baseline echography performed by an experienced rheumatologist (1° echographist) were included
There were two groups of patients: group # 1 patients were injected without echography guidance, and group # 2 patients were injected under echography guidance by the advanced echography rheumatologist (2° echographist)
After the procedure was done, patients had their carpal joint rested for 24 hours. Corticosteroid and Disease-Modifying Drugs levels were unchanged during two weeks after the injection.
Two weeks after the injection, patients returned for a control echography with Gray Scale and Power Doppler; this was conducted by echographist # 1(2nd evaluation).
RESULTS: There were 25 patients, 88 % female with a mean age of 51.84 years (SD±13.9). From the previous group, only 19 patients received glucocorticoids with an average dose of 6.2 mg/day (SD±2,5); (chart 1). Concerning basal echography and Gray Scale, in the group of non-guided injection, all patients (100%) had positive results; in the guided group 91,67 % had positive results; there were no significant differences between the groups (p-value: 0.32).
In the blinded injection group, 38,46 % of the patients had a negative control echography Gray Scale result, whereas in the guided group, 50 % of patients had a negative Gray Scale resuts. In the blinded group, 61,54 % of the patients had a negative Power Doppler result, whereas in the guide group 75 % of patients had a negative result (p-value: 0,67); (chart 1).
CONCLUSION: In the present work, we have not found significant differences between performing a guided vs a blinded intra-articular carpal injections in patients with RA and carpal synovitis. Therefore, the usefulness of carpal- guided intraarticular injections should be considered in every case.
TREATMENT WITH RECOMBINANT CYSTATIN 3 FROM FASCIOLA HEPATICA IMPROVES COLLAGEN-INDUCED ARTHRITIS
Mirian Farinon1,2, Renata Ternus Pedó1,2, Thales Hein da Rosa1,2, Bárbara Jonson Bartikoski1,2, Thaís Evelyn Karnopp1,2, Martin Pablo Cancela Sehabiague3, Henrique Bunselmeyer Ferreira3, and Ricardo Machado Xavier1,2. 1Laboratório de Doenças Autoimunes, Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 2Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 3Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Objectives: To evaluate the therapeutic effect of recombinants cystatin 1 and cystatin 3 from Fasciola hepatica in a mice model of collagen-induced arthritis (CIA).
Materials and methods: Twenty-seven DBA/1J mice were induced with CIA by an injection of collagen type-II and Freund’s adjuvant at days 0 and 18. Animals were randomly divided into three groups: vehicle (n=9, treated with phosphate-buffered saline), cystatin 1 (n=9, treated with 100 μg/dose of recombinant cystatin 1) and cystatin 3 (n=9, treated with 100 μg/dose of recombinant cystatin 3). Treatment started after day 18 by intraperitoneal injection once a day until the end of the experiment, at day 45 after CIA induction. Clinical arthritis score, nociception, paw edema, body and spleen weight were evaluated. Lymphocytes were isolated from lymph nodes and CD4+CD25+Foxp3+ T regulatory subset was assessed by flow cytometry. Data are expressed as mean ± SEM and were evaluated by one-way or two-way ANOVA followed by Bonferroni post-test.
Results: Treatment with cystatin 1 did not alter any of the analyzed parameters. On the other hand, cystatin 3 was able to reduce clinical arthritis score from day 38 with 32% of reduction at day 45 (9.22±1.22) compared to vehicle (13.56±0.73) (p<0.05). In addition, treatment with cystatin 3 diminished nociception (cystatin 3: 4.0±0.36g, vehicle: 2.7±0.32g) (p<0.05) and paw edema (cystatin 3: 0.051±0,012ml, vehicle: 0.093±0.007ml) (p<0.05). Moreover, the treatment did not alter body weight (cystatin 3: 21.67±0.31g, vehicle: 21.05±0.38g) and spleen weight (cystatin 3: 7.04±0.31, vehicle: 7.16±0.38), as well as the T regulatory population (cystatin 3: 63.38±3.66%; vehicle: 58.31±6.77%).
Conclusion: Treatment with cystatin 3 improved collagen-induced arthritis by attenuating the disease score, nociception and paw edema. Moreover, the treatment did not induce body weight loss or spleen weight alterations. These results suggest that recombinant cystatin 3 from Fasciola hepatica has the potential as a treatment for inflammatory and autoimmune diseases such as RA.
THE ROLE OF GROW DIFFERENTIATION FACTORS (GDF) 8, 11, 15 ON MUSCLE WASTING IN COLLAGEN INDUCED ARTHRITIS MODEL
Bárbara Bartikoski1,2, Mirian Farinon1,2, Thales Hein da Rosa1,2, Renata Ternus Pedó1,2, Thais Karnopp1,2, Jordana Miranda de Souza1,2, and Ricardo Machado Xavier1,2. 1Laboratório de Doenças Autoimunes, Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre Ramiro Barcelos, Porto Alegre, Brazil, 2Faculdade de Medicina, Universidade Federal do Rio Grande do Sul Ramiro Barcelos, Porto Alegre, Brazil.
Objectives: To evaluate muscle expression of GDF-8, GDF-11 and GDF-15 throughout the development of experimental arthritis (CIA). Collagen-induced arthritis was induced in DBA1/J mice.
Materials and Methods: Male DBA/1J mice, between 8 and 12 weeks of age, were randomly divided into five experimental groups: healthy controls used as baseline gene expression standards (HC, n=6), control animals without intervention euthanized at 25 days of experimentation (CO, n=8), collagen-induced arthritis animals euthanized at 25 days of experimentation (CIA, n=8) to evaluate initial arthritis, control animals without intervention euthanized at 50 days of experimentation (CO, n=8) and collagen-induced arthritis animals euthanized at 50 days of experimentation (CIA, n=8) to evaluate established arthritis. During the experimental period, disease score, edema, and grip strength were evaluated. Mice were euthanized at day 0. 25 or 50 days after induction of arthritis. The tibio-tarsal joints were collected for confirmation of disease development. The tibialis anterior and gastrocnemius muscles were weighed and processed for the evaluation of myofiber cross-sectional area (CSA) and for the assessment of GDF-8, GDF-11 and GDF-15 gene expression by RT-qPCR.
Results and conclusions: The CIA group had significantly higher arthritis scores and larger hind paw edema volumes than CO at initial and established disease (25 and 50 days after disease induction). The CIA had decreased grip strength at both time points compared to CO. Sarcoplasmic ratios and muscle weight were also reduced in CIA at established disease. The tibialis anterior CSA was reduced in CIA at established disease compared with the CO (p=0.026). GDF-11 levels were increased in CIA at initial disease and tended to be higher at established disease (p=0.004, p=0.07, respectively). GDF-8 expression was decreased at established disease (p=0.004) and GDF-15 do not differ between groups. A negative correlation between muscle strength and GFD-11 was found at initial disease (r=-71 p=0.071). At initial arthritis, GDF-11 mRNA expression is increased and also associated with loss of grip strength, while GDF-8 gene expression is reduced at established disease, possibly as a compensatory mechanism. Thus, the GDFs may have a role in muscle atrophy and loss of strength in the CIA model, and it is worthwile to explore this in RA patients.
PRIMARY SJOGREN SYNDROME WITH A VERY UNCOMMON CASE OF MONOCHORIONIC DIAMNIOTIC TWINS EXPOSED TO MATERNAL ANTI-RO/SSA AUTOANTIBODIES WITH DISCORDANT DISEASE EXPRESSION – CASE REPORT
Priscila Dias Cardoso Ribeiro1, Germana Ribeiro Araujo Carneiro de Lucena1, Flavia Maria Melo Matos Campos Peixoto1, Edgard Torres dos Reis Neto1, and Emilia Inoue Sato1. 1Unifesp, São Paulo/ Sp, Brazil.
Introduction: Congenital complete heart block (CHB) in the absence of structural abnormalities is a rare condition and has been associated with high levels of maternal anti-Ro/SSA antibodies. Even when anti-Ro/SSA antibodies are present in sera of mothers with autoimmune rheumatic diseases, its incidence varies from 1-2% of live births. Prior studies have concluded that the transference of the antibody across the placenta is necessary but not sufficient for the expression of CHB on fetus. We present a very uncommon case of monochorionic diamniotic twins (male twin A and male twin B) exposed to maternal anti-Ro/SSA autoantibodies with discordant disease expression in a patient of primary Sjogren Syndrome.
Case report: M.O.G., 35 years-old, diagnosed with primary Sjogren’s Syndrome (xerophthalmia, xerostomia, rheumatoid factor 3590 IU, Anti-Ro/SSA and Anti-La/SSB positive, ANA 1/640 Speckled pattern and polyclonal hypergammaglobulinemia) was referred to a fertilization clinic because of the diagnosis of infertility due to uterine tubal dysfunction. Besides that, she presented anticardiolipin IgM 68 MPL and 74MPL (12 weeks apart) without previous thrombotic events. After the second procedure of in vitro fertilization, the patient started a monochorionic diamniotic twin pregnancy. As the patient presented anti-Ro/SSA and anti-La/SSB positive antibodies, she was submitted to weekly fetal echocardiogram between pregnancy weeks 16 and 24. By the 23rd week, one of the fetus presented CHB on the echocardiogram while the cardiac image and frequency of the other fetus was normal. Dexamethasone 4mg/day was immediately started without CHB reversal. The twins were born at the 33th gestational week, both with good Apgar scores and appropriate weights. Similar levels of Anti-Ro/SSA antibodies in the sera of both children were found (A 461; B 436). After 15 days, a pacemaker was implanted successfully in the fetus with CHB.
Conclusion: The association of fetal/neonatal CHB with maternal anti-Ro/La antibodies is well established. However, this case supports the hypothesis that besides the exposure to anti-Ro/SSA, other unclear causal factors are involved in the genesis of CHB, since the two monochorionic fetuses were exposed to the same maternal antibody, but only one developed the disease. Efforts should aim to identify better biomarkers and unraveling further the molecular mechanisms leading to this pathology in the hope of developing effective therapies to prevent or treat CHB.
CYTOMEGALOVIRUS DISEASE OF THE UPPER GASTROINTESTINAL TRACT IN A PATIENT WITH GRANULOMATOSIS POLYANGIITIS
Germana Ribeiro Araujo Carneiro de Lucena1, Priscila Dias Cardoso Ribeiro1, Daniel Viana da Silva1, Alexandre Wagner da Silva Souza1, and Emilia Inoue Sato1. 1Unifesp, São Paulo/ Sp, Brazil.
Introduction: The Cytomegalovirus (CMV) is an opportunistic infection reported in immunocompromised patients, such as those with rheumatic diseases, which might cause serious complications both by an acute disease or by a reactivation. Data related to CMV affecting the digestive tract are limited in patients with reumathologic diseases.
Case report: Man, 55 years old, Caucasian, natural from Suzano/SP. Diagnosed with granulomatosis with polyangiitis (GPA) in September 2017 due to multiple cranial nerve syndromes, affecting the 2nd, 7th and 8th pairs, visual acuity reduction on the left eye and amaurosis on the right one, facial paralysis, lymphocytic aseptic meningitis in 2016, pulmonary nodule in September 2017 and necrotizing renal vasculitis. In addition, he had a diagnose of primary immunoglobulin deficiency. Previously treated with cyclophosphamide, rituximab, prednisone and human immunoglobulin. In January 2019, he developed intense upper abdominal pain, associated with nausea, involuntary weight loss of 6 kg, night sweats and daily fever, along with severe daily headache and reduced visual acuity on the left side. In April 2019, he was admitted for clinical investigation, undergoing upper digestive endoscopy (EGD), which revealed an ulcerated and infiltrative lesion of the distal esophagus, cardia and upper portion of the stomach. He also did have an echoendoscopy that showed the presence of ulcerated lesions along the esophagogastric transition with fourth-layer invasion. Considering malignant neoplasia the most probable cause, he did have a chest and abdomen tomography; both were normal. By MRI of the head and a tomography of the paranasal sinus there were nosigns of disease activity or metastasis. The biopsy showed the presence of nuclear alterations, suggestive of viral infection, immunohistochemically there wasevidence of the presence of CMV. At the ophthalmologic examination, retinal detachment was evidenced, probably associated with the viral infection. Serology for CMV showed a positive IgG 30.09, non-reactive IgM, quantification of CMV DNA 112980 copies, strongly positive. Thus, he was diagnosed with CMV gastric ulcer and he underwent ganciclovir treatment for 21 days. After he completed this treatment, he did jave a new EGD that showed complete resolution of the ulcer. A new PCR-CMV showing < 500 copies.
Conclusion: Immunosuppressive therapy for rheumatic diseases is an important risk factor for the development of CMV, cyclophosphamide being the most commonly involved agent; in addition, hypogammaglobulinemia is also a risk factor for this infection. Giventhe seriousness of this condition, this diagnosis should always be considered in rheumatology patients using immunosuppressive therapy.
PYODERMA GANGRENOSUM-LIKE ULCERATIONS IN GRANULOMATOSIS WITH POLYANGIITIS: A CASE REPORT
Germana Ribeiro Araujo Carneiro de Lucena1, Priscila Dias Cardoso Ribeiro1, Edgard Torres dos Reis Neto1, and Emilia Inoue Sato1. 1Unifesp, São Paulo/ Sp, Brazil.
Introduction: Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis that affects small e medium vessels characterized by granulomatous inflammation involving the upper and lower respiratory tracts. It belongs to the group of vasculitis associated with ANCA, usually associated to the cytoplasmic pattern (c-ANCA), which is directed against proteinase 3 (PR3). Skin and mucosal involvement occurs in 15-50% of the cases, and in 13% of the cases might be the initial clinical manifestation. The cutaneous lesions might be of the polymorphic type, including palpable purpura, blisters, vesicles, papulo-nodular and livedo-reticularis. In addition, ulcerative lesions with elevated erythematous-violet borders mimicking pyoderma gangrenosum (PG) are reported as the rarest cutaneous presentation of GPA, representing approximately 1% of the cases, not only affecting lower limbs, but also affecting the face or other sites more rarely.
Case report: A male patient, 45 years old, born in and coming from São Paulo, Brazil. He had a history of repeated upper airway infections from childhood, which were treated with antibiotics, and pulmonary tuberculosis treated in 2007. By 2017, a painful erythematous nodular cutaneous lesion with purulent and ulcerative secretion with erythematous-violaceous border, affecting trunk and zygomatic bilaterally, characteristic of PG ensued. He also presented fever, night sweats and involuntary weight loss of 8 kg, as well as reduction of visual acuity. It evolved with paralysis of vocal cords and pulmonary nodules. A biopsy of a pulmonary lesion was performed and it revealed a chronic, circumscribed inflammatory process with a granulomatous pattern affecting small blood vessels, characterized by a plasmacytic infiltrate with giant cell reaction and areas of necrosis with exudate, adjacent parenchyma with extensive areas of alveolar hemorrhage, compatible with GPA. The ANCA, indirect immunofluorescence, was negative. The magnetic resonance imaging of the sinuses revealed bone erosions of the nasosinusal soft tissues. After GPA diagnosis, he underwent pulse therapy with corticosteroids and cyclophosphamide and progressed with clinical improvement and healing of cutaneous lesions.
Conclusion: We describe a case of GPA associated with cutaneous ulcerations with PG-like features. The skin lessions can be differentiated from the histology, which presents a neutrophilic inflammatory infiltrate mainly affecting lower limbs and rarely the face and trunk. GPA is suggested by the presence of positive c-ANCA and systemic involvement, especially with pulmonary involvement. Summarizing, the diagnosis of GPA is quite difficult, skin lesions might help in early diagnosis, implying an improvement in morbidity associated with pathology.
FASCIOLA HEPATICA EXTRACT AND ITS THERAPEUTIC EFFECT ON SYNOVIAL FIBROBLASTS FROM PATIENTS WITH RHEUMATOID ARTHRITIS.
Thales Hein1,2, Suelen Pizzolatto Dalmolin1,2, Renata Ternus Pedó1,2, Mirian Farinon1,2, Jordana Miranda de Souza Silva1,2, Vanessa Rax3, Eduardo Cremonese Filippi Chiela2,4, Martín Pablo Cancela Sehabiague2,5, Henrique Bunselmeyer Ferreira2,5, Rafaela Cavalheiro do Espírito Santo1,2, Fabiany da Costa Gonçalves da Costa Gonçalves6, and Ricardo Machado Xavier2,3. 1Laboratório de Doenças Autoimunes Hospital De Clínicas De Porto Alegre, Porto Alegre, Brazil, 2Universidade Federal Rio Grande do Sul, Porto Alegre, Brazil, 3Serviço de Reumatologia, Hospital de Clínicas de Porto Alegre, Porto Alegre, Porto Alegre, Brazil, 4Departamento de Ciências Morfológicas, ICBS, Serviço de Pesquisa Experimental- Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil, 5Departamento de Biologia Molecular e Biotecnologia, Porto Alegre, Porto Alegre, Brazil, 6Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
Objectives: To evaluate the therapeutic effect of a extract from Fasciola hepatica (F. hepatica) on synovial fibroblasts from rheumatoid arthritis (RA) patients.
Materials and methods: Fibroblast-like synoviocytes (FLS) were isolated from synovial fluid of RA patients. Cultures of FLS were exposed at different concentration of F. hepatica extract (60μg/mL, 80μg/mL and 100μg/mL) and analyzed after 24h, 48h and 72h by MTT cell viability assay. The effect of extract was also evaluated by cell adherence, wound healing and invasion, apoptosis assay, nuclear morphometric index (NMI), and TNF-α production. Statistical analysis were performed with ANOVA or Student’s tTest and p<0.05 was considered statistically significant.
Results:F. hepatica extract decreased the cell proliferation of FLS at concentration of 100 μg/mL after 48h (83.8 % ± 5.0 extract vs 100.0 % ± 0.0 control; p<0.05), and at concentrations of 80 μg/mL (88.4 % ± 3.0 extract vs 100.0 % ± 0.0 control; p<0.05) and 100 μg/mL (89.8 % extract ± 3.8 extract vs 100.0 % ± 0.0 control; p<0. 05) after 72h, when compared with control group. Based on these results, the dose of 100 μg/mL for 48h was chosen for the following tests. The treatment with F. hepatica extract showed a decreased of FLS adherence (92.0 cells ± 5.8 extract vs 116.3 cells ± 7.9 control; p<0.05), migratory potential (69.5 % ± 17.6 extract vs 100.0 % control; p<0.05) and cell invasion (80.3 % ± 3.9 extract vs 100.0 % control; p<0.05). Moreover, there was a trend of decreased TNF levels after extract treatment. However, the F. hepatica extract does not affect NMI parameters or induce cell death on FLS. Taken together, our results point out F. hepatica extract as a potential treatment for RA due to their ability to reduce the aggressive and invasive profile of FLS.
PRIMARY ANTIPHOSPHOLIPID SYNDROME (PAPS) SUCH AS CUTANEOUS THROMBOTIC MANIFESTATION AND DIFFUSE ALVEOLAR HEMORRHAGE, CASE REPORT.
Pamela Wurmann Kiblisky1, Pedro Zamorano Soto1, Claudia Hernandez Spiess1, Claudio Karsulovic Cvitanich1, and Maria Paz Poblete De La Fuente1. 1Hospital Clinico Universidad De Chile, Santiago, Chile.
65-year-old male. Since August 2018, cervical painful swelling and 3 repeated deep and superficial vein thrombosis episodes. PET CT was performed ruling-out hidden cancer, and Dabigatran permanent treatment was started. 2 months later patient referred a new large swelling episode in the suprapubic and scrotal area. An ecographic Doppler study showed testicular ischemia, for which he underwent symptomatic and anticoagulant treatment. Autoantibodies test were negative. During the ensuing months, 2 more episodes of swollen and painful areas in the periorbital region and the right lower limb occurred. A cutaneous biopsy of the periorbital regions showed medium vessel thrombotic vasculopathy and mild inflammatory infiltrate of a medium size vessel, rising polyarteritis nodosa as the main diagnostic possibility.
After several months of glucocorticoid treatment, and during tapering down period patient relapsed and a new skin biopsy were performed. The same medium vessel thrombotic vasculopathy was found. Azathioprine was initiated at 2 mg/kg/day, adding corticosteroids and cyclophosphamide due to lack of response. During the third cyclophosphamide cycle, the patient referred thoracic pain, cough and new laboratory test performed showed increase in systemic inflammation. An extensive lung study was performed: Thoracic CT Scan showed centrolobulillar ground glass infiltrates and bronchioalveolar lavage (BAL) ruled-out cancer and infectious disease. Echocardiogram rule out pulmonary hypertension. Rheumatologic studies showed: lupus anticoagulant (+), AntiB2GPI IgG (+) 59.9, anticardiolipin antibodies (-), Direct Coombs test (+), ANCA (-), ANA (-), normal range C3 y C4, anti-dsDNA(-).
Patient persisted with dyspnea, severe anemia ensued and a new BAL showed alveolar hemorrhage. 3 grs. Methilprednisolone were started and 60 mg prednisone during follow-up with slow progressing tapper down. After initial symptoms' remission, mycophenolate mofetil and hydroxychloroquine were added consolidating clinical and laboratory response.
This is a rare case describing primary APS featuring thrombotic vasculopathy and alveolar hemorrhage as main manifestations. Lung involvement in APS is unusual; when it occurs it is manifested by pulmonary hypertension secondary to pulmonary embolism. In our case, the diagnosis of PAPS was delayed because of atypical clinical and demographic presentation and repeated negative autoantibody tests. Anticoagulation treatment was insufficient and major immunosuppression was necessary to achieve remission. It is important to be aware of this atypical presentation of primary APS to establish early anticoagulation and immunosuppressive therapy.
BIOMARKER LEVELS FOLLOWING INTRAVENOUS BELIMUMAB IN CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS SUPPORT BENEFICIAL EFFECTS ON DISEASE ACTIVITY: RESULTS FROM THE PLUTO STUDY
Hermine I. Brunner1, Diego O. Viola2, Manuel A. Ferrándiz3, Carlos Abud-Mendoza4, Damon Bass5, Anne Hammer5, Mohamed Okily6, Gina Eriksson5, Nicolino Ruperto7, and for the Paediatric Rheumatology International Trials Organisation (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG). 1Cincinnati Children's Hospital Medical Center, Cincinnati, United States, 2Instituto CAICI, Reumatologia, Rosario, Argentina, 3Instituto Nacional de Salud del Niño, Reumatologia, Breña, Perú, 4Hospital Central “Dr Ignacio Morones Prieto”, Unidad Regional de Reumatologia y Osteoporosis, Hospital Central and Facultad de Medicina de la Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico, 5GlaxoSmithKline, Collegeville, United States, 6GlaxoSmithKline, Uxbridge, UK, 7IRCCS Istituto Giannina Gaslini, Clinica Pediatrica e Reumatologia, PRINTO, Genoa, Italy.
Objectives: PLUTO (GSK study BEL114055; NCT01649765), a randomized, placebo-controlled, double-blind study, evaluated efficacy and safety of intravenous (IV) belimumab in children with childhood-onset systemic lupus erythematosus (cSLE). Primary and secondary endpoints have been presented; briefly, SRI4 and PRINTO/ACR responses numerically favored belimumab over placebo.1 Here, we report changes in biomarker levels with belimumab treatment.
Methods: Eligible patients (5–17 years) received monthly belimumab 10 mg/kg IV or placebo, plus standard cSLE therapy. Biomarker level percentage changes from baseline at Week 52 was assessed for: serum immunoglobulin G (IgG), anti-dsDNA antibody and C-reactive protein (CRP; in patients positive [anti-dsDNA ≥30 IU/ml, CRP ≥4 mg/L] at baseline), complement C3, complement C4 (both in patients with low baseline levels: C3 <90 mg/dl, C4 <10 mg/dl), and B cells (CD19+, CD20+, memory [CD19+/20+/27+; also assessed at Week 4], naïve [CD19+/20+/27-]). Comparisons are descriptive.
Results: Ninety-three patients were randomized (placebo, N=40; belimumab, N=53). From baseline to Week 52, median percentage changes for belimumab patients decreased for total and naïve B cells, IgG, anti-dsDNA, and CRP; and increased for C3 and C4, versus placebo (Table). In belimumab patients, memory B cells approximately doubled by Week 4 (median percentage change 220.4% vs 16.7% with placebo) and decreased towards baseline values (11.7% vs 0% with placebo) by Week 52.
Conclusions: In children with cSLE, reductions in total and naïve B cells, IgG, and anti-dsDNA levels, increase in complement levels, and the rapid memory B-cell increase followed by a subsequent slow decline with IV belimumab were consistent with adult trials and support its beneficial effects in cSLE.
Study funding: GSK. Editorial support (GSK-funded): Fishawack Indicia Ltd, UK.
1Brunner HI, et al. Arthritis Rheumatol. 2018; 70(suppl 10): abstract 2867.
MEDICATION ADHERENCE AMONG PATIENTS WITH RHEUMATOID ARTHRITIS
Pedro Santos-Moreno1, Fernando Rodriguez-Florido1, Diana Carolina Buitrago-Garcia2, and Guillermo Sanchez-Vanegas2. 1Biomab, Bogotá, Colombia, 2Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
Objectives: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease, is associated with joint damage and disability, RA is considered to have a high burden for the patient, its family, the society and the health systems. The main therapeutic goal for patients with RA is to achieve low disease activity and to minimize disability. Patients may choose not to follow the treatment prescription due to beliefs or myths related to the RA drugs. A convenient method for measuring the level of adherence is the Morisky Medication Adherence Scale, which also provides insight into possible remedies for low adherence. The aim of this study is to investigate the adherence to pharmacological therapy in patients with RA and establish its correlation with disease activity.
Methods: A descriptive cohort study was conducted. Data were collected through a survey and review of medical records. The participants’ medication adherence level was assessed while using the Modified eight-point Morisky Scale (MMAS-8). MMAS-8 is a validated survey method with high reliability and validity used to evaluate the level of adherence to medication for chronic diseases. In this study, we classified patients as adherents with a score of 6 or more. Descriptive epidemiology was done, we calculated means, and standard deviations for continuous variables and categorical variables were presented as rates.
Results: We included 251 patients and all of them completed the survey, 93% were female, mean age was 59 years ±9.8. 38% of the patients had finished high school and 37% had higher education. According to employment, 53% were economically inactive participants, 28% were employed and 19% were pensioners. Most patients received conventional DMARDS 55%, mean DAS28 was 2.58 ±1.19. Regarding medication adherence 30% of patients were adherent to the therapy, 60% reported to forget sometimes their medication, but only 28% forgot to take them when they were traveling or not at home and, 42% of patients reported that sometimes they forget to take their medications. There was no statistical association between disease activity, age and adherence to therapy.
Conclusions: Medication non-adherence among patients with RA is high. Further investigations are needed to better understand the reasons for non-adherence and to establish interventions for improving patient outcomes.
THE EFFECTS OF AN EDUCATIONAL PROGRAM FOR PATIENTS WITH RHEUMATOID ARTHRITIS. CAN WE CHANGE MYTHS, BELIEFS AND BEHAVIORS? LESSONS FROM THE RHEUMATOID ARTHRITIS PATIENT’S UNIVERSITY PROJECT IN COLOMBIA
Fernando Rodriguez-Florido1, Pedro Santos-Moreno1, Diana Carolina Buitrago-Garcia2, Guillermo Sánchez-Vanegas2, Maria Mercedes Rueda-Gutierrez1, and Zohelia Castaño-Sierra1. 1Biomab, Bogotá, Colombia, 2Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
Objectives: Rheumatoid arthritis (RA) is a chronic condition that is considered as one of the most common causes of disability. RA affects from 0.5% to 1% of the worldwide population. It has been demonstrated that patient education plays a relevant role in the adherence to treatment and changes in lifestyle among patients. The aim of this study is to describe the perceptions of the team who started a structured educational project for patients with RA.
Methods: During 2019, we implemented an educational project called UNIVERSITAR: University for patients with rheumatoid arthritis. The program is planned to last two years and the main objective is to have patients with high expertise regarding all aspects related to RA. The first year the program included 307 patients with RA and the objective was to provide education for three levels. At the same time, we established an interdisciplinary team that provided educational workshops for the patients; a rheumatologist with experience in centers of excellence for RA leaded the team.
Results: During this first year, the project has been successful. Patients considered our educational program as a great opportunity to be involved with their disease process. We found that there are many myths and wrong beliefs related to RA and within each class, patients had the opportunity to clarify them. It is noteworthy that patients usually consult internet, social networks or newspapers when they have questions related to RA instead of asking the health care team. Additionally, the teachers in charge of the program understood that although we planned a high intensity program, we needed to be flexible in order to achieve patient’s compliance. Finally, we found that it’s important to incorporate a motivational component to the program in order to include this activity to the patient´s life goals.
Conclusions: This an innovative program that has demonstrated to be widely accepted by patients with RA. It integrates the patient as an active component into our RA educational program. The program has solved many questions related to all aspects related to the disease, giving as a result empowering patients that are committed to all aspects involved in their treatment.
QUALITY OF LIFE IN PATIENTS WITH RHEUMATOID ARTHRITIS WHO ENROLLED IN AN EDUCATIONAL PROGRAM IN A SPECIALIZED CENTER IN COLOMBIA
Fernando Rodriguez-Florido1, Pedro Santos-Moreno1, Diana Carolina Buitrago-Garcia2, and Guillermo Sanchez-Vanegas2. 1Biomab, Bogotá, Colombia, 2Fundación Universitaria de Ciencias de la Salud, Bogotá, Colombia.
Objectives: The measurement of Quality of life (QoL) approaches multidimensional characteristics taking into account the course of life, happiness, and the way human beings perceive their current situation, health and functioning. It has been demonstrated that Rheumatoid arthritis (RA) might decrease quality of life, due to its impact in physical pain and function (1). We aimed to describe the quality of life in patients with RA.
Methods: We performed a cross-sectional study. We included patients with confirmed RA diagnosis that were enrolled in an educational program in a specialized RA center. We collected sociodemographic data, and markers of disease activity as DAS28. We applied the Spanish version of the RA Quality of Life Questionnaire (RAQoL); the scale has a score from one to ten where a score of 10 is associated with better quality of life. We excluded patients with psychological or psychiatric disorders and illiterate participants. We performed a bivariate analysis in order to explore the relationship between disease activity and quality of life.
Results: We included 251 patients, 93% were female, mean age was 59 years ±9.8. Regarding occupation, 71% were retired and 29% were employed, additionally, 40% of participants finished high school, 23% elementary school, 21% had college education and 16% finished trade school. Regarding disease activity, mean DAS28 was 2.58 ± 1.19. Mean RAQoL score was 59 ± 11. The higher scores in the scale were the domains regarding family support and interaction. See table 1. We did not find statistical association between RAQoL score and DAS28.
Conclusion: In general, our patients reported a mean score of 60 points, thus we can assume that they have a moderate quality of life. As other studies have shown, the domain related to family and friends support had higher scores, and the lowest were pain and arthritis. Due to the above, it is relevant to create strategies such as educational programs in order to support the improvement of aspects with the lowest scores such as pain or nervous tension. Finally, in order to improve the quality of life of patients with RA, health professionals have to consider these results when prescribing a treatment for a patient with RA.
HEALTHCARE COSTS IN RHEUMATOID ARTHRITIS ACCORDING TO DISEASE ACTIVITY IN THE COLOMBIAN HEALTH SYSTEM
Julieth Carolina Castillo Cañon1, Ana Maria Valbuena Garcia, Paul Alejandro Mendez Patarroyo, Andres R. Fernandez A, and Lizbeth Acuña1. 1Cuenta de Alto Costo, Bogotá, Colombia.
Objective: To compare the healthcare costs in Rheumatoid Arthritis (RA) according to disease activity categories.
Methods: Cross-sectional study of secondary data from Colombian High Cost Diseases Fund. We included all RA patients with information about healthcare costs, who were cared for and reported by the Colombian health insurance from July 1, 2017 to June 30, 2018. Two groups of patients were compared according to the scope or not of the therapeutic goals of RA [DAS 28 <3.2 (remission and low activity) and DAS 28≥3.2 (moderate and high activity)]. The median and interquartile range (IQR) for Disease-modifying anti-rheumatic drugs (DMARD) costs, care, incapacity to work and total cost (the sum of all costs) were reported. The Mann-Whitney U test was used to analyze the costs difference between the groups.
Results: 7,004 RA patients were analyzed, 66.88% were in remission or low activity. The age median was 57 years (IQR 49-66) for group in remission or low activity and 56 years (IQR 46-65) for group in moderate or high activity. The median evolution time was 5,91 years (IQR 2,49-12,50) versus 5,49(IQR 2,14-12,50). The median DMARD costs was 28,25 United States dollar (USD) ($7,57-$180,44) for the first group while the second was 53,49 USD ($11,37-$810,40), the median cost of care in the first group was 217,21 USD ($56,95-$562,29) and in the second of 261,16 USD ($65,29-$1.100,36). The biggest difference between the groups is due to the costs related to work disabilities (1 USD [$1 - $58, 22] vs 51, 09 USD [$1 - $284, 04]). The median total cost was 242, 56 USD [$61,86 - $600,77] versus 282,61 USD [$69,90 – 1.222,62]. The differences between costs according to activity were significant in all cases.
Conclusions: RA in remission or low activity represents lower costs for the Colombian health system compared with patients with DAS28≥3.2, given mainly by costs of inability to work. Thus, the scope of therapeutic objectives in patients with RA has not only effects on patients, but also savings for the health system.
THE UNIVERSITY OF BARCELONA ULTRASOUND SCORE FOR SARCOPENIA: VALIDITY AND RELIABILITY.
Ingrid Moller1, Maribel Miguel-Pérez2, Juan Blasi-Cabus3, Lene Terslev4, Hilde Berner Hammer5, and Carlo Martinoli3. 1Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences (Bellvitge Campus), University of Barcelona, Spain. Instituto Poal de Reumatologia, Barcelona, Spain, 2Unit of Human Anatomy and Embryology, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences (Bellvitge Campus), University of Barcelona, Spain, Barcelona, Spain, 3Unit of Histology, Department of Pathology and Experimental Therapeutics, Faculty of Medicine and Health Sciences (Bellvitge Campus), University of Barcelona, Spain, Barcelona, Spain, 4Center for Rheumatology and spine diseases, Rigshospitalet, Denmark, Denmark, 5Hammer Dept of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway, Oslo, Norway, 6Cattedra di Radiologia "R"-DICMI, Universita di Genova, Genoa, Italy, Genova, Italy.
Objectives: Sarcopenia (Sp) is a multifaceted muscle disease and constitutes a challenging health problem. Sp constitutes an independent factor of morbidity and mortality and entails an increase in healthcare costs. Currently there is no ultrasound (US) scoring system for Sp nor is there a scoring system for gross anatomical changes in the Sp muscle or for the histological changes. Musculoskeletal ultrasound (MSUS) is increasingly used in clinical settings and musculoskeletal research.
Methods: In order to validate the US assessment of the muscle and their changes due to Sp the aims of the current study were: to asses the accuracy, feasibility and reproducibility of ultrasound for the measurement of the muscle thickness and the cross-sectional area of two muscles as compared to similar measurements in cadaver specimens and to develop a semiquantitative ultrasound scoring system for assessment of the Sp muscle by correlating the score of the ultrasound image with the corresponding score for gross anatomical specimen and the score of the histological images and test the reliability of the scoring system between the observers.
Results: The results show good interobserver reproducibility for both the ultrasound evaluation of the cross-sectional muscle area (intraclass correlation coefficient [ICC] 0.9660; p<0,0001) and muscle thickness (ICC 0.5, p<0,0001). In all cases this reliability has excellent p value so the intraobserver reliability has not been calculated; since there was excellent reliability between observers, we can rest assured that there is also a good intra-observer agreement. Interobserver reliability for the scoring system was excellent, with agreement in 9 out of 10 specimens between US and histology.
Conclusions: MSUS is an accurate and reliable tool for measurement the thickness and the cross-sectional area of the appendicular muscle. A novel semiquantitative ultrasound score system is introduced and found to be reproducible and adequately correlated with anatomical and histological findings. This score can be applicable for the longitudinal evaluation of sarcopenic patients.
A PROPOS OF A CASE OF SYSTEMIC SCLEROSIS SINE SCLERODERMA
Andrea Gabriela Cosios Sarmiento1, Martha Inga Jacome1, Leydi Villareal1, and Srta Leslye Daniela Garcia Cuenca1. 1Hospital Isidro Ayora, Loja, Ecuador.
Introduction: Systemic sclerosis (SS) is a generalized disease of the connective tissue, characterized clinically by thickening and fibrosis of the skin (scleroderma) and by affecting internal organs, predominantly heart, lungs, kidneys and gastrointestinal tract. Systemic sclerosis is divided into diffuse SS, limited SS and SS without scleroderma which is characterized by internal organ involvement, vascular alterations (Raynaud's phenomenon) and absence of skin fibrosis. While it is true that SS without scleroderma is a pathology of low prevalence and incidence, it is estimated that approximately 1 / 6,500 adults are affected. It predominantly affects women (the female: male ratio is approximately 4: 1). Its etiology and pathogenesis are unknown; it presents vascular, immunological and collagen abnormalities. Histologically, it is characterized by accumulation of an excess of collagen and other constituents of the extracellular matrix. The morbidity and mortality of SS is directly related to the extent and severity of the visceral condition.
Objective: To present a clinical case of a patient with SS without scleroderma with interstitial lung disease with fibrosis and pulmonary hypertension.
Case report: A 63-year-old woman with no personal or family pathological history was admitted to the hospital with functional class III – IV dyspnea plus perioral cyanosis, a grade II murmur in the tricuspid area and pulmonary level, disseminated cracking thighs, limbs, presence of peripheral venous networks, positive Raynaud's phenomenon, ecchymosis and hematomas of spontaneous onset; it was decided to complement with echocardiogram (severe pulmonary hypertension type III), chest CT scan (severe pulmonary hypertension type III, pulmonary interstitial abnormalities suggestive of a connective tissue disease); antinuclear antibodies were positive (6.8), cenp-B was positive, anti-intrusion was 205.4 and anti scl70 was 1 (negative).
Discussion: Systemic Sclerosis without Scleroderma is a rare variety of Systemic Sclerosis in which patients have visceral disease in the absence of characteristic skin changes. The first cases in the United States were published in 1954 by Abraham et al. In Latin America the first publication was made in Brazil in 2013; of the total number of patients with scleroderma, only 8.3% of them had this variant. The diagnosis in this subtype of SS is delayed by the absence of cutaneous involvement. In these patients, pulmonary involvement (fibrosis) and pulmonary hypertension are the main causes of morbidity and mortality.
DIFFUSE ALVEOLAR HEMORRHAGE IN SYSTEMIC LUPUS ERYTHEMATOSUS – CASE REPORT
Vitória Siqueira1, Natasha Santos1, Camila Bentes1, and Marcela Alves1. 1Santa Casa De Misericórdia Do Pará, Belém, Brazil.
The survival rate of diffuse alveolar hemorrhage (DAH) is extremely low leading to acute catastrophic hemoptysis with impaired oxygenation, ventilation or hemodynamic instability. DAH, to date, remains one of the most devastating complications in SLE patients because of its high mortality; it thus represent a diagnostic and therapeutic challenge for the rheumatologist.
Case Report: Male patient, 51 years old, farmer, with arthritis and polyarthralgias associated with recurrent low fever, myalgia, asthenia, headache, chest pain accompanied by cough and dyspnea, abdominal pain with episodes of diarrhea, weight loss of 10 kg and petechiae of the lower limbs. On admission, he had normochromic normocytic anemia, evidence of inflammatory activity, consumed complements, decreased total protein and albumin, and increased channel enzymes. Prednisone 60 mg/day was started, with improvement of the general picture, pending the results of autoantibodies, hydroxychloroquine therapy 400 mg/day was introduced, and cyclophosphamide pulse therapy was planned. Nevertheless, the patient progressed with worsening of his general condition, fever, asthenia, dyspnea requiring continuous use of oxygen, increased abdominal volume (ascites), decreased hemoglobin and leukocytosis with left deviation, and decreased renal function. Emergence of intense hemoptysis, respiratory discomfort with desaturation, and intubation with large volume of blood through the orotracheal tube. The patient developed cardiopulmonary arrest and resuscitation maneuvers were unsuccessfully initiated.
Comments: DAH is rare, but it is a potentially catastrophic manifestation with high mortality, known to complicate connective tissue disorders. Among the rheumatological autoimmune diseases, it occurs most frequently in patients with SLE and systemic vasculitis. It results from the accumulation of red blood cells in the alveolar space which originate from the alveolar capillaries. It is associated with high mortality ranging from 23% to 92%, usually with systemic infection as the terminal event. Active lupus nephritis with hypoalbuminemia is an important risk factor. DAH is typically defined by the presence of three major components: (1) signs (blood return on bronchoscopy) or symptoms (dyspnea, cough, hemoptysis) of pulmonary hemorrhage, (2) new fall in hemoglobin (usually 1.5 to 2 g). / dL) and (3) new diffuse infiltrates in the chest images. The gold standard diagnostic test for pulmonary hemorrhage is the bronchoalveolar lavage, which shows bleeding in the airways and / or macrophages soaked with hemosiderin. There are currently no therapeutic guidelines for this life-threatening manifestation of SLE due to the rarity of the condition.
PREVALENCE OF BURNOUT SYNDROME IN RHEUMATOLOGISTS IN URUGUAY
Natalia Cestau Flores1, Iliana Rosas Zuluaga1, and Andrea Vargas Peña1. 1Servicio de Reumatología Facultad de Medicina Universidad de la República, Montevideo, Uruguay.
Introduction: The Burnout syndrome is defined as a state of physical, mental and emotional exhaustion, caused by chronic working exposure to stressful emotional circumstances. There is a high personal demand at medical work which can cause occupational stress, leading to worsening quality of life.
Objective: To evaluate the prevalence of burnout syndrome and its demographic and occupational factors, in rheumatologists and rheumatologists in training.
Methods: This descriptive and observational study included all the rheumatologists in practice, who were associate with the Uruguayan Rheumatology Society by December of 2019 (N=104). Patients who did not complete the form or did not consent to participate in the study were excluded; thus, 89 individuals where included (85,58%). We used anonymous questionnaires, in paper and digitally, taken into account social, demographic, personal and occupational aspects. We apply the Maslach Burnout Inventory Human Services for Medical Personnel to evaluate the 3 subscales from Burnout syndrome, which are; emotional fatigue, depersonalization and personal fulfillment.
Microsoft Access Database Engine 2010 was used to build the database and JASP 0.11.1 for analysis. We calculated the mean, the median and the central tendency for the variables under study, and the Chi-square test was performed for qualitative variables with a p-value of 0.05.
Results: 73% were women, more than 30% of them were between the ages of 51 and 60. 56% were married. 33,7% have a weekly workload greater than 40 hours and 64% worked not only in public areas, but also in private ones. 61,8% consider suffering occupational stress and 74,1% felt professionally fulfilled. 41% did not feel respected by colleagues from other medical areas, and 79% considered that the time spent with the patients was not enough. Regarding the subscales, 28% have a high risk of emotional fatigue and 24,7% a moderate risk. 12, 4% have a higher risk of depersonalization and the 19,1% a moderate risk. 67,4% felt lack of personal fulfillment and 68,5% have two subscales in moderate or high risk.
Conclusions: 8,9% of the surveyed presented high risk of Burnout syndrome and 2,2% moderate risk. 100% of those who have a high and moderate risk of Burnout syndrome, considered suffering occupational stress. We did not find significant relation between burnout, emotional fatigue, depersonalization and lack of personal fulfillment with the social, demographic, personal and occupational variables studied.
USE OF RIVAROXABAN IN ANTIPHOSPHOLIPID SYNDROME: SERIES OF 22 CASES
Erick Daniel Quijivix Gonzalez1, Nilmo Noel Chavez Pérez1, Estuardo Anzueto1, Silvia Rivera1, Axel Estuardo Diaz Cancinos1, Valeria Rodriguez Carcamo1, Gilbert Genaro Martinez Gomez1, and Marlon Reynerio Arita Alvarado1. 1Instituto Guatemalteco De Seguridad Social, Guatemala, Guatemala.
Objective: Rivaroxaban has been used for anticoagulation in antiphospholipid syndrome (APS) when warfarin cannot be used for some reason. We describe our experience with rivaroxaban for secondary prophylaxis in patients with APS treated at the Guatemalan Social Security Institute.
Methods: Search and clinical review of patient data that met the 2006 Sydney classification criteria for APS, being monitored in the last 6 years and treated with rivaroxaban 20 mg/day and aspirin 100 mg/day.
Results: 22 patients were evaluated, 17 (77%) women, 12 (54%) with secondary APS associated all with SLE, mean age of 37 years and a mean of 12 years of disease duration; 45% had deep vein thrombosis in limbs, 27% pulmonary thromboembolism, 23% cerebrovascular event and 14% venous sinus thrombosis. 50% of the patients had IgG and 68% IgM aCL in high titers. After an average of 701 days after initiating rivaroxaban, new thrombotic events occurred in 9 (41%) of the patients, with recurrent venous thrombosis sites in upper limbs in 33%, in lower limbs in 22%, pulmonary thromboembolism in 33% and acute myocardial infarction in 12%. The 22 patients also used aspirin 100 mg/day. 2 (9%) patients had vaginal bleeding and 1 died secondary to acute myocardial infarction.
Conclusions: Of the 22 patients who used rivaroxaban at a dose of 20 mg/day associated with aspirin 100 mg/day, 41% presented a new thrombotic event, with an average of 701 days after starting treatment.
FACTORS ASSOCIATED WITH SEXUAL DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS
Sindy Melissa Sánchez Romo1, Griselda Serna Peña1, Miguel Ángel Villarreal Alarcón1, Octavio Ilizaliturri Guerra1, Ana Laura De León Ibarra1, Iván de Jesús Hernández Galarza1, and Dionicio Ángel Galarza Delgado1. 1Hospital Universitario “Dr. José Eleuterio González”, Monterrey, México.
Introduction: Rheumatic diseases of autoimmune origin affect all aspects of life including sexual function.
Objective: To determine the frequency of sexual dysfunction (SD) and its relationship with the level of disease activity, fatigue, psychological state and comorbidities in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
Methods: We included 80 patients of legal age with active sexual life who were cared for at our rheumatology clinic. We applied the following surveys: Arizona Sexual Experiences Scale (ASEX), Hospital Anxiety and Depression Scale (HADS) and Functional Assessment of Chronic Illness Therapy (FACIT). Their level of disease activity was evaluated by DAS-28 and SLEDAI.
Results: Of the total of 80 patients, 61 (76.3%) had RA and 19 (23.8%) SLE with an average age of 43.9 (+/- 12) years. Regarding the level of activity, 43.8% were in remission, 18.8% in low activity, 31.3% in moderate activity and 6.3% in high activity. Around 48.8% had sexual dysfunction. According to the HADS survey, 30% had symptoms of anxiety and 21% of depression; and according to the FACIT survey, 28.8% had severe fatigue. 65% of the patients had comorbidities; the most prevalent were osteoporosis (20%), fibromyalgia (18.8%) and arterial hypertension (11.3%).
Patients with SD showed a higher prevalence of anxiety symptoms (p = 0.010) and depression (p = 0.042), severe fatigue (p = 0.005), were older (p = 0.003) and had some comorbidities (p = 0.008). No statistically significant differences weres found between the disease activity level scores and sexual dysfunction (p = 0.273).
Conclusions: Sexual dysfunction was common in almost half of our patients. We found that regardless of the level of disease activity, the factors significantly associated with sexual dysfunction were symptoms of anxiety and depression, severe fatigue, older age and the presence of comorbidities.
RELATIONSHIP BETWEEN DISEASE ACTIVITY AND WORK PRODUCTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS
Sindy Sánchez Romo1, Griselda Serna Peña1, Miguel Ángel Villarreal Alarcón1, Iván de Jesús Hernández Galarza1, and Dionicio Ángel Galarza Delgado1. 1Hospital Universitario "Dr. José Eleuterio González", Monterrey, México.
Introduction: Rheumatic diseases are chronic inflammatory diseases that affect the patient's quality of life, including his/her working life.
Objective: To find the relationship that exists between the level of disease activity and work productivity assessing: the percentage of work time lost due to their health (absenteeism), the degree to which their disease affected labor productivity (presentism) and percentage of disability in their daily activities due to their illness (disability).
Methodology: Rheumatoid arthritis (RA) patients from the rheumatology clinic of the university hospital “Dr. José Eleuterio González”, to whom the Work Productivity and Activity Impairment (WPAI) survey was applied were included. The disease activity level was evaluated using the DAS-28-PCR calculator.
Results: 110 patients with RA were included. The mean age was 52.8 (+/- 13.14) years and the mean disease duration was 98.5 (+/- 118) months. Around 57.7% were either on remission or had low disease activity, and 41.4% were in a moderate and severe level of disease activity. Only 28 (25.45%) patients had an economically paid job; of them, 5 (17.85%) patients reported missing work (absenteeism) due to their health in the preceding week, which represents 27.38% of their work time. While they were at work (presenteeism), 33.93% of real hours were lost due to health problems; out of work (disability) occurred in36.43% of the patients.
Through a Spearman correlation analysis, a significant correlation was found between the level of disease activity and presentism (p = 0.029) and disability (p = 0.035).
Conclusions: Work productivity in patients with economically paid job is affected in patients with a moderate and severe level of the disease activity.
PREVALENCE OF INTERSTITIAL LUNG DISEASE IN LATIN-AMERICAN PATIENTS WITH RHEUMATIC DISEASES
Sindy Sánchez Romo1, Miguel Ángel Villarreal Alarcón1, and Dionicio Ángel Galarza Delgado1. 1Hospital Universitario "Dr. José Eleuterio González", Monterrey, México.
Introduction: Interstitial lung disease (ILD) is the most common manifestation of rheumatic lung disease. Respiratory manifestations cause significant morbidity and mortality in patients with rheumatic diseases. We need a consensus on the prevalence of this disease in our patients.
Objective: To find the prevalence of ILD in patients with rheumatic diseases.
Methodology: The medical records of patients who were cared for at the rheumatology clinic of hospital "Dr. José Eleuterio González” from January 2019 to December 2019 were evaluated Demographic and diagnostic data were obtained.
Results: We included1728 patients, of whom only 65 (3.8%) had a diagnosis of interstitial pneumopathy confirmed by high-resolution computed tomography. Of these 65 patients, 92.3% were women and had a mean age of 55.6 (+/- 14.26) years. The most frequent rheumatic diseases were rheumatoid arthritis (RA) with 19 patients (29.2%), systemic sclerosis (SSc) with 17 (26.2%), seven with myositis (10.8%) and seven with Antisynthetase syndrome (ASS) (10.8%).
Of the total patients (1728), around 100% of patients with ASS, 33.3% of patients with MCTD, 26.3% of patients with UCTD, 25% of patients with SSc, 7.5% of the patients with Sjogren's syndrome (SjS) and only 1.9% of the patients with RA had ILD.
Of the total number of patients (1728), 35 (2.0%) were found to have an abnormal chest x-ray film but did not have a confirmed diagnosis of ILD by HRCT. It was also found that 93 (5.4%) patients had concomitant symptoms of dyspnea and cough, but without diagnostic tests for ILD.
Conclusions: Early detection of ILD is a challenge for rheumatologists. Compared to the literature, we have a lower prevalence of ILD in patients with RA, SSc and SjS. Taking into account that there is a percentage of patients with abnormal radiographs and suggestive symptoms without diagnostic confirmation studies, we believe that there is a subdiagnosis of ILD in our population. A new algorithm for identifying risk factors and screening should be implemented to make an early diagnosis of ILD and improve survival.
AUTOIMMUNE LIVER DISEASE IN PATIENTS WITH PRIMARY SJÖGREN’S SYNDROME
Nadia Riscanevo1, Flavia Ceballos1, Janet Flores1, Elisa Novattix1, Diego Baenas1, Francisco Caeiro1, and Alejandro Alvarellos1. 1Hospital Privado Universitario De Córdoba, Córdoba, Argentina.
Introduction: Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease characterized by the destruction and infiltration of lymphoplasmacytic cells from exocrine glands, associated to keratoconjunctivitis and xerostomia which affect mainly middle aged women. Hepatic manifestations are frequently found in patients with pSS including primary biliary cirrhosis and autoimmune hepatitis.
Objectives: 1. Describe the clinical and serological features of patients with and without hepatic involvement and to compare the main differences between these groups.
2. Determine and compare the mortality rate between populations with and without autoimmune liver disease.
3. Determine the prevalence of autoimmune liver disease.
Methods and materials: A total of 157 patients, age ≥ 18 years with a diagnosis of pSS were included in this study, from two third-level hospitals during a period of 9 years from 2009 to 2018. Patients fulfilled the American-European Consensus Group Criteria (2002) and those patients with a diagnosis of Secondary Sjögren’s Syndrome and viral infection were excluded.
Design of the study: We conducted a descriptive, medical records review cross-sectional study. The diagnosis of liver disease was established by clinical manifestations, laboratory data (increased alkaline phosphatase, GOT/GPT, the presence of antimitochondrial antibodies, anti-smooth muscle antibodies, anti-liver, kidney microsomal antibodies) and/or liver biopsy.
Statistical analysis: Continuous and categorical variables were compared with Mann Whitney and Fisher’s tests, respectively with a 95% confidence interval and a p-value < 0.05 indicated a statistical significance. We did a global analysis comparing the groups of patients with diagnosis of liver associated disease. The prevalence of liver associated disease was calculated.
Results: 95% of the patients included in the study were women (n=150) with a mean age of diagnosis of 52.1 years (DS 13.5). We found that Raynaud phenomenon was significantly more frequent in the group of patients with hepatic involvement (44% vs 6.8% p: 0,004). Moreover, there were no significant differences in other clinical manifestations, laboratory data and salivary gland biopsies grading No deaths occurred in the period studied; however, 17.7% of patients were lost to follow-up (n=28/157).
Conclusions: 1. The prevalence of pSS and liver associated disease was 5.6% in the period studied and similar results have been published by others.
- We found an association between the presence of Raynaud phenomenon and autoimmune liver disease.
BLISTERING LESIONS / WOUNDS AS A MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
José Adolfo Sánchez1, Gabriela Ramos2, and Daniela Alonso López2. 1Artros, Salta, Argentina, 2Hospital San Bernardo, Salta, Argentina, 3Hospital San Bernardo, Salta, Argentina.
Introduction: The cutaneous manifestations of systemic lupus erythematosus (SLE) occur in 75 % of patients. Less than 5 % of cases present blistering lupus. This manifestation is common in young black skinned women between the ages of 20 and 40 years. In the literature, it has been described as associate with the occurrence of lupus nephritis and to be associated with a serious diagnosis and refractory illness.
Clinic Case: 20-year old patient, without previous known past medical history. The patient started with unilateral parotid hypertrophy, asymmetric arthralgias of small and medium size joints, painful oral and nasal ulcers; subsequently tense blister wounds appeared in the perioral region, thorax, abdomen and proximal extremities. In addition, painful circinate erythematous and cyclical pruritic lesions appeared on gluteus, neck, upper extremities and hands. Besides, sicca symptoms, photosensitivity, distal paresthesia and itching occur. Classical complementary studies were requested (ANA 1/160, homogeneous and peripheral, anti-DNA 1/40, anti-Sm positive, anti-SSA positive, C3 positive, C3 18, C4 46, Proteinuria 1,78 g/24 hours, skin biopsy, kidney and glands with defining characteristics. SLE diagnosis was confirmed with dermatological and renal involvement. Pulses of methylprednisolone and mycophenolate mofetil 3 grams a day were prescribed, followed by oral corticosteroids and hydroxychloroquine with slow response. Patient achieved remissions in six months.
Discussion: Bullous lupus can be the beginning of SLE or can appear during the disease course. The diagnosis is based on the Sharma shirt criteria. The clinical presentation is an acute painful blistering eruption generalized not limited to photo exposed areas, present mainly on chest, arms, hands, head and neck. The oral and genital mucosal are affected in 51% of cases. Some extra cutaneous manifestations are present in 50 % of patients. Most of them are class III or IV lupus nephritis The serological evidence includes the positive presence of ANA, anti-dsDNA, anti-Ro, anti- La, anti-Sm, anti-RNP and low complement. The chosen treatment is dapsone. Glucocorticoids, azathioprine, mycophenolate mofetil, methotrexate, rituximab and cyclophosphamide are use according to extent and seriousness of the skin involvement
Conclusion: Bullous systemic lupus is an autoimmune blistering disorder and it is rarely the initial clinical manifestation of SLE; it can be associated with nephritis. The importance of early recognition and differentiation of the blistering pathology so that early treatment can be implemented is emphasized Its association with systemic involvement, frequently the renal one needs to be also emphasized.
ROLE OF A NAILFOLD CAPILLAROSCOPY IN THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASES
Silvana Saavedra1, Karen Vergara1, Claudia Hernández1, Tamara Palavecino1, and Felipe Reyes1. 1Hospital Clínico Universidad De Chile, Santiago, Chile.
Introduction: Nailfold capillaroscopy (NFC) is a non-invasive technique used in patients with Raynaud's phenomenon (RF) for the early diagnosis of connective tissue diseases (CTD). Interstitial lung disease (ILD) may be the first manifestation of CTDs (ILD-CTD), before extrapulmonary signs or positive autoantibodies are manifested. There are limited data on the role of NFC in patients with ILD and suspected CTD.
Patients and methods: Medical records review study of 51 patients referred to our center for NFC as a diagnostic support for ILD were included. The NFC was performed using a USB digital microscope (Dino-Lite AM4115-N2UT). The information obtained was examined by a multidisciplinary team in accordance with current guidelines to obtain a definitive diagnosis.
Discrete variables were expressed as absolute value (percentage with respect to the group) and continuous variables are expressed as arithmetic mean +/- standard deviation. For the comparison of baseline data between groups, the Exact Fischer Test and Anova Test were used.
Results: 51 patients (84.3% women) were studied, with radiological patterns in the HRCT of non-specific interstitial pneumonia (39.6%), usual interstitial pneumonia (18.8%) and unclassifiable pattern (22.9%). 27.5% were Rheumatoid factor positive and 86.8% had a positive antinuclear antibody (ANA) with variable titer and pattern. The diagnoses prior to the NFC were interstitial pneumonia with autoimmune features 29.2%, scleroderma 10.5% and idiopathic interstitial pneumonia 31.3%. The most frequent NFC findings were nonspecific alterations of the microcirculation (46.4%) and scleroderma pattern (53.5%). 54.9% of the patients presented a positive NFC (27 patients), supporting the diagnosis in 51.9% and a change of diagnosis in 33.3% of the cases.
Conclusions: ILD may be the first form of presentation of a CTD, so before considering an ILD as idiopathic interstitial pneumonia, it is essential to conduct a complete clinical study and the patient be evaluated by a multidisciplinary team. NFC, like the extended serology and salivary gland biopsy, can be very useful in the diagnosis of ILD-CTD.
SPONDYLARTHRITIS IN THE DOMINICAN REPUBLIC: ANALYSIS OF CLINICAL AND EPIDEMIOLOGICAL CHARACTERISTICS.
Karen Franco1, Ricardo Vásquez2, Jossiell Then3, Julissa Paula1, Milka Alvarez1, Teresandris Polanco1, and Paola Gottschalk4. 1Hospital Dr. Moscoso Puello, Santo Domingo, Dominican Republic, 2Hospital Dr. Darío Contreras, Santo Domingo, Dominican Republic, 3Hospital Metropolitano De Santiago (HOMS), Santiago, Dominican Republic, 4Clínica Unión Médica, Santiago, Dominican Republic.
Summary: The term spondylarthritis (SpA) describes a group of rheumatic diseases with common immunogenetic, clinical and radiographic characteristics. They are classified as ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis (PsA), arthritis associated with inflammatory bowel diseases and undifferentiated spondylarthritis. The prevalence of these clinical entities in the Dominican population is unknown1.
Objectives: To describe the clinical and epidemiological characteristics of patients with spondylarthritis in Dominican Republic.
Materials and methods: A multicenter, descriptive study was carried out in three rheumatology departments in the Dominican Republic: Dr. Francisco Moscoso Puello (HFMP) and Dr. Dario Contreras (HDDC) Hospitals in Santo Domingo and Metropolitan Hospital of Santiago (HOMS) to evaluate SpA´s patients. Clinical and epidemiological data, imaging studies and type of treatment were examined. Data analysis was performed with the Epi-Info 7.0 program.
Results: A total of 130 SpA´s patients were included: HFMP (43.8%), HDDC (28.5%) and HOMS (27.6%). A predominance for the male sex was observed (56.1%). The mean age was 43.3 ± 12.2 years. SpA was more frequent in mixed race patients (50%) compared to the Caucasian and black populations. AS occurred in 57.6%, PsA in 26.1%, arthritis associated with inflammatory bowel disease in 3.8%, reactive arthritis in 2.3%, juvenile ankylosing spondylitis in6.1%, uveitis HLA-B27(+) in3% and undifferentiated spondylarthritis in0.76%. The association of at least one first degree relative with the disease was observed in 24% of the cases. HLA-B27 was positive in 62.3% of the patients. Sacroiliitis by MRI was documented in 51.5% of patients with AS. Patients required biological therapy with anti-TNF (52.3%), anti-IL-17 (20%), anti-IL-23 (2%) and there was a 25% response rate with non-biological DMARDs.
Conclusions: The epidemiological characteristics of the patients with spondylarthritis in our country do not differ from those published in other studies worldwide2;the high frequency in mixed race, could be due to the fact that this is our predominant population, The highest frequency of SpA patients in the Eastern part of the country attracted attention, perhaps related the complicated genetic ancestry described in that part of the population3. The most common manifestation corresponded to peripheral arthritis. It is proposed to carry out studies with a larger number of patients and establish national registries.
POST-INFECTIOUS ANEURYSM ASSOCIATED WITH CYTOMEGALOVIRUS PRIMO INFECTION, WITH CLINICAL MANIFESTATIONS OF INCOMPLETE KAWASAKI DISEASE IN THE HOSPITAL FOR EL NIÑO POBLANO
Luis Alberto Aparicio Vera1, and Alejandra Silva Hernandez1. 1Hospital Para El Niño Poblano, Puebla, México.
Introduction: Kawasaki disease is the most frequent vasculitis in pediatrics. Its etiology is not well established, but an association with infectious processes has been reported. The differential diagnosis should include other etiologies, especially when the presentation of the disease is unusual.
Presentation of clinical case: The clinical case of a 14-month-old girl is presented; at the time of admission, she was suspected of having Kawasaki disease, due to a febrile condition> 5 days, desquamation in palms and plants and conjunctival injection, echocardiogram with findings of two aneurysms in both coronaries. Admission laboratory tests included hypoalbuminemia, normochromic normocytic anemia, thrombocytosis (915,000/cu mm), general urine examination with more than 10 cells / field, abundant urinary sediment and CRP> 96 mg / dl; all these manifestations put together correspond to a case of Incomplete Kawasaki disease. pulse IV methylprednisolone was started; proteinuria, hematuria, arterial hypertension and hypertriglyceridemia ensued. A more ample differential diagnoses was entertained; nodal panarteritis was ruled out in the renal biopsy which demonstrated absence of vasculitis in small and medium caliber vessels with positive viral inclusions for cytomegalovirus. A second dose of gamma globulin was administered, because of persistent fever. With an adequate therapeutic response. the girl was discharged.
Conclusions: This case illustrates the clinical manifestations of Kawasaki like-disease, with histopathological diagnosis of cytomegalovirus infection, an association previously mentioned in other publications. This association is extremely rare. It is important to consider CMV in the differential diagnosis of atypical or incomplete Kawasaki disease.
FACTORS ASSOCIATED WITH THE TIME OF PRESENTATION OF CARDIOVASCULAR EVENTS IN A COHORT OF COLOMBIAN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Juan Camilo Diaz-Coronado1,2, Sebastián Herrera-Uribe1, Diego Rojas-Gualdrón3, Laura Betancur-Vásquez2, Daniel Gonzalez-Hurtado2, Juanita Gonzalez-Arango2, Laura Uribe-Arango2, Maria fernanda Saavedra2, Jorge Lacouture-Fierro2, Santiago Monsalve2, Sebastian Guerra2, Jose david Serna-Giraldo2, Juan David Lopez2, Julian Barbosa2, Deicy Hernández-Parra1, and Ricardo Antonio Pineda-Tamayo1. 1Grupo de Información Clínica Artmedica IPS, Medellín, Colombia, 2Departamento de Medicina Interna, Universidad CES, Medellín, Colombia, 3Facultad de Medicina, Universidad CES, Medellín, Colombia.
Objective: To examine the clinical and immunological characteristics associated with time to severe renal involvement in patients with Systemic Lupus Erythematous in a Colombian cohort followed for one year, between January 2015 and December 2018.
Methods: Medical records review follow-up study of patients with SLE that fulfilled either the 1987 American College of Rheumatology Classification Criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Patients with cardiovascular disease outcomes such as angina, acute myocardial infarction, stroke, transient cerebral ischemia and chronic arterial occlusive disease were included. Patients who did not have at least two follow-up measurements or had structural heart disease, valvulopathies, arrhythmias, myocarditis and pericarditis were excluded. The main outcome was defined as the time from diagnosis to cardiovascular disease occurrence.
Clinical and immunological characteristics were examined. Descriptive statistical analyses of participant data during the first evaluation are reported as frequencies and percentages for categorical variables, and as medians and interquartile ranges for quantitative variables. Age and sex adjusted survival functions and Hazard Ratios (HR) with 95% confidence intervals and p-values were estimated using parametric Weibull models for interval-censored data. p values < 0.05 were considered statistically significant.
Results: 547 patients were included: 29 were left-censored as they presented renal involvement at entry, 22 were interval censored as outcome occurred between study visits, and 496 were right-censored as involvement was not registered during follow-up. 528 (96.5%) patients were female, median age at entry was 46 (IQR = 23) and median age to diagnosis was 29.4 (IQR = 20.9). Statistically significant age and sex adjusted variables were High Blood Pressure (HBP) HR = 2.0 (95%CI 1.1-3.6; p-value <0.018) and cumulative prednisolone dose (>10 gr vs <2 gr) HR = 2.4 (95%CI 1. 1-5.1; p-value = 0.023). Figure 1 shows the age and sex adjusted survival function for HBP.
Conclusion: In patients with lupus, HBP and cumulative steroid doses accelerate the onset of cardiovascular diseases more than two times. Maintaining blood pressure within the normal range and tapering glucocorticoids as allowed by the clinical manifestations could improve outcomes in these patients who are already considered to have a high cardiovascular risk.
FACTORS ASSOCIATED WITH TIME TO SEVERE LUPUS NEPHRITIS IN A COHORT OF COLOMBIAN PATIENTS
Juan Camilo Diaz-Coronado1,2, Sebastián Herrera-Uribe1, Diego Fernando Rojas-Gualdrón3, Laura Betancur-Vásquez2, Daniel Gonzalez-Hurtado2, Juanita Gonzalez-Arango2, Laura Uribe-Arango2, Maria Fernanda Saavedra2, Jorge Lacouture-Fierro2, Santiago Monsalve2, Sebastian Guerra2, José David Serna-Giraldo2, Juan David Lopez2, Julian Barbosa2, Deicy Hernández-Parra1, and Ricardo A. Pineda-Tamayo1. 1Grupo de Información Clínica Artmedica IPS, Medellín, Colombia, 2Departamento de Medicina Interna, Universidad CES, Medellín, Colombia, 3Facultad de Medicina, Universidad CES, Medellín, Colombia.
Introduction: Systemic lupus erythematosus (SLE) clinical manifestations, and their severity, vary according to age, ethnicity and socioeconomic status. Both Hispanic and Afro-Americans have a higher incidence and more sever presentation when compared to Caucasian patients with SLE.
Objective: To examine the clinical and immunological characteristics associated with time to severe renal involvement in patients with Systemic Lupus Erythematous in a Colombian cohort followed for one year, between January 2015 and December 2018/
Methods: Medical records review follow-up study. Patients with SLE diagnosis that fulfilled either the 1987 American College of Rheumatology Classification Criteria for SLE or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. We included patients with diagnosis of lupus nephritis according to the Wallace and Dubois criteria. Patients who did not have at least two follow-up assessments or had a defined cause of nephritis other than lupus were excluded. The main outcome was defined as time from diagnosis to severe renal involvement defined as a creatinine clearance ≤50 ml/min, 24-hour proteinuria ≥3.5 grams or end-stage renal disease.
We analyzed clinical and immunological characteristics. Descriptive statistical analyses of participant data during the first evaluation are reported as frequencies and percentages for categorical variables, and as medians and interquartile ranges (IQR) for quantitative variables. Age and sex adjusted survival functions and Hazard ratios (HR) with 95% confidence intervals and p-values were estimated using parametric Weibull models por interval-censored data. p values < 0.05 were considered statistically significant.
Results: 548 patients were included: 67 were left-censored as they presented renal involvement at entry, 6 were interval censored as outcome occurred between study visits, and 475 were right-censored as involvement was not registered during follow-up. 529 (96.5%) patients were female, median age at entry was 46 (IQR = 23) and median age at diagnosis was 29.5 (IQR = 20.6) years. 67% were Mestizo, 13% Caucasian and 0.3% Afro-Colombian. Age and sex adjusted variables associated with time to severe lupus nephritis were high blood pressure HR = 3.5 (95%CI 2.2-5.6; p-value <0.001) and anti-Ro antibodies (per unit increase) HR = 1.002 (95%CI 1.001-1.004; p-value = 0.04). Figure 1 shows age and sex adjusted survival function.
Conclusion: In our cohort severe lupus nephritis occurred in less than 15% of patients at 10 years. Both high blood pressure and elevated anti-Ro titers were associated with a higher rate of severe lupus nephritis occurrence.
POTENTIALLY MODIFIABLE FACTORS RELATED TO POOR QUALITY OF LIFE IN ANKYLOSING SPONDYLITIS
Francisco Zevallos1, Manuel F. Ugarte-Gil1,3, Mariela Medina-Chinchon1, Rocío V. Gamboa-Cardenas1, Mariano Cucho-Venegas1, José Alfaro-Lozano<