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Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

Casanova, M J MD, PhD1; Chaparro, M MD, PhD1; García-Sánchez, V MD, PhD2; Nantes, O MD, PhD3; Leo, E MD4; Rojas-Feria, M MD, PhD5; Jauregui-Amezaga, A MD, PhD6; García-López, S MD, PhD7; Huguet, J M MD8; Arguelles-Arias, F MD, PhD9; Aicart, M MD10; Marín-Jiménez, I MD11; Gómez-García, M MD, PhD12; Muñoz, F MD13; Esteve, M MD, PhD14; Bujanda, L MD, PhD15; Cortés, X MD, PhD16; Tosca, J MD, PhD17; Pineda, J R MD, PhD18; Mañosa, M MD, PhD19; Llaó, J MD20,21; Guardiola, J MD, PhD22; Pérez-Martínez, I MD, PhD23; Muñoz, C MD, PhD24,52; González-Lama, Y MD, PhD25; Hinojosa, J MD, PhD26; Vázquez, J M MD27; Martinez-Montiel, M P MD28; Rodríguez, G E MD29; Pajares, R MD30; García-Sepulcre, M F MD, PhD31; Hernández-Martínez, A MD32; Pérez-Calle, J L MD33; Beltrán, B MD, PhD34; Busquets, D MD35; Ramos, L MD36; Bermejo, F MD, PhD37; Barrio, J MD38; Barreiro-de Acosta, M MD, PhD39; Roncedo, O MD40; Calvet, X MD, PhD41; Hervías, D MD42; Gomollón, F MD, PhD43; Domínguez-Antonaya, M MD44; Alcaín, G MD, PhD45; Sicilia, B MD, PhD46; Dueñas, C MD47; Gutiérrez, A MD, PhD48; Lorente-Poyatos, R MD49; Domínguez, M MD50; Khorrami, S MD51; Taxonera, C MD, PhD53; Rodríguez-Pérez, A MD, PhD54; Ponferrada, A MD, PhD55; Van Domselaar, M MD56; Arias-Rivera, M L MD57; Merino, O MD58; Castro, E MD59; Marrero, J M MD60; Martín-Arranz, M MD61; Botella, B MD62; Fernández-Salazar, L MD, PhD63; Monfort, D MD64; Opio, V MD65; García-Herola, A MD, PhD66; Menacho, M MD67; la Piscina, Ramírez-de P MD68; Ceballos, D MD, PhD69; Almela, P MD, PhD70; Navarro-Llavat, M MD71; Robles-Alonso, V MD72; Vega-López, A B MD73; Moraleja, I MD74; Novella, M T MD75; Castaño-Milla, C MD76; Sánchez-Torres, A MD77; Benítez, J M MD2; Rodríguez, C MD3; Castro, L MD9; Garrido, E MD10; Domènech, E MD, PhD19; García-Planella, E MD20; Gisbert, J P MD, PhD1

American Journal of Gastroenterology: January 2017 - Volume 112 - Issue 1 - p 120–131
doi: 10.1038/ajg.2016.569

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.

METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.

RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn’s disease and ulcerative colitis patients, respectively. In both Crohn’s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01–1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07–3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27–2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13–2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09–2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn’s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51–0.87) and age (HR=0.98; 95% CI=0.97–0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.

CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

1Department of Gastroenterology Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain

2Hospital Universitario Reina Sofía, Córdoba, Spain

3Complejo Hospitalario de Navarra and Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain

4Hospital Universitario Virgen del Rocío, Sevilla, Spain

5Hospital Universitario de Valme, and CIBEREHD, Sevilla, Spain

6Hospital Clínic i Provincial, and CIBEREHD, Barcelona, Spain

7Hospital Universitario Miguel Servet, Zaragoza, Spain

8Consorcio Hospital General Universitario de Valencia, Valencia, Spain

9Hospital Universitario Virgen Macarena, Sevilla, Spain

10Hospital Universitario Ramón y Cajal, Madrid, Spain

11Hospital Universitario Gregorio Marañón and Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain

12Hospital Universitario Virgen de las Nieves, Granada, Spain

13Complejo Universitario de León, León, Spain

14Hospital Universitario Mutua Terrassa, and CIBEREHD, Terrassa, Spain

15Hospital Universitario de Donostia, Instituto Biodonostia, Universidad del País Vasco UPV/EHU, and CIBEREHD, Donostia, Spain

16Hospital de Sagunto, Valencia, Spain

17Hospital Clínico Valencia, Valencia, Spain

18Complejo Hospitalario Universitario de Vigo, Vigo, Spain

19Hospital Universitari Germans Trias i Pujol, and CIBEREHD, Badalona, Spain

20Hospital de la Santa Creu I Sant Pau, Barcelona, Spain

21Hospital Sant Joan de Deu, Manresa, Spain

22Hospital Universitario de Bellvitge, Barcelona, Spain

23Hospital Universitario Central de Asturias, Oviedo, Spain

24Hospital de Basurto, Bilbao, Spain

25Hospital Universitario Puerta de Hierro, Madrid, Spain

26Hospital de Manises, Valencia, Spain

27Hospital Juan Ramón Jiménez, Huelva, Spain

28Hospital Universitario Doce de Octubre, Madrid, Spain

29Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain

30Hospital Universitario Infanta Sofía, Madrid, Spain

31Hospital General Universitario de Elche, Alicante, Spain

32Hospital Torrecárdenas, Almería, Spain

33Hospital Universitario Fundación de Alcorcón, Madrid, Spain

34Hospital Universitario La Fe, and CIBEREHD, Valencia, Spain

35Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain

36Hospital Universitario de Canarias, La Laguna, Spain

37Hospital Universitario de Fuenlabrada, Madrid, Spain

38Hospital Universitario Río Hortega, Valladolid, Spain

39Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain

40Hospital Villafranca de los Caballeros, Toledo, Spain

41Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, and CIBEREHD, Sabadell, Spain

42Hospital Virgen de Altagracia, Ciudad Real, Spain

43Hospital Clínico Lozano Blesa, Instituto de Investigación Sanitaria Aragón (IIS Aragón), and CIBEREHD, Zaragoza, Spain

44Hospital Universitario de Móstoles, Móstoles, Spain

45Hospital Virgen de la Victoria, Málaga, Spain

46Hospital Universitario de Burgos, Burgos, Spain

47Hospital Universitario San Pedro Alcántara, Cáceres, Spain

48Hospital General Universitario de Alicante, and CIBEREHD, Alicante, Spain

49Hospital General de Ciudad Real, Ciudad Real, Spain

50Hospital General San Jorge, Huesca, Spain

51Hospital Universitario Son Espases, Palma de Mallorca, Spain

52Hospital Virgen de la Salud, Toledo, Spain

53Hospital Universitario Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain

54Hospital Universitario De Salamanca, Salamanca, Spain

55Hospital Universitario Infanta Leonor, Madrid, Spain

56Hospital de Torrejón de Ardoz, Madrid, Spain

57Hospital Universitario Severo Ochoa, Madrid, Spain

58Hospital Universitario Cruces, Barakaldo, Spain

59Hospital Lucus Augusti, Lugo, Spain

60Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain

61Hospital Universitario La Paz, Madrid, Spain

62Hospital Universitario Infanta Cristina, Madrid, Spain

63Hospital Clínico Universitario de Valladolid, Valladolid, Spain

64Consorci Sanitari Terrassa, Terrassa, Spain

65Hospital Universitario de Getafe, Madrid, Spain

66Hospital Marina Baixa, Alicante, Spain

67Hospital Joan XXIII, Tarragona, Spain

68Hospital Universitario de Álava, Vitoria, Spain

69Hospital Universitario Dr Negrín, Las Palmas de Gran Canaria, Spain

70Hospital General Universitario de Castellón, Castellón, Spain

71Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain

72Hospital Universitari Vall d’Hebron, Barcelona, Spain

73Hospital de Viladecans, Barcelona, Spain

74Hospital de Galdakao-Usansolo, Galdakao, Spain

75Hospital Can Misses, Eivissa, Spain

76Hospital Universitario Rey Juan Carlos, Madrid, Spain

77Hospital Virgen de la Arrixaca, Murcia, Spain

Correspondence: J.P. Gisbert, MD, PhD, Gastroenterology Unit, La Princesa Hospital, Diego de León, 62, 28006 Madrid, Spain. E-mail:

Received 09 April 2016; accepted 04 October 2016

Guarantor of the article: J.P. Gisbert, MD, PhD.

Specific author contributions: M.J. Casanova, M. Chaparro, and J.P. Gisbert conceived and designed this study. All the authors participated in the collection of data of patients. M.J. Casanova, M. Chaparro, and J.P. Gisbert analyzed and interpreted the results and wrote the manuscript. All the authors critically reviewed the manuscript, and have read and approved the final version of the manuscript.

Financial support: None.

Potential competing interests: M.J. Casanova has received research funding from Abbott; J.P. Gisbert and M. Chaparro have served as speakers, consultants, and advisory members for and have received research funding from MSD and Abbvie; E. Domenech has served as a consultant and an advisory board for MSD and Abbott, and has received research funding from MSD and Abbott; F. Gomollón has received fees for conferences and received grants for assistance to scientific meetings from Abbott and MSD; X. Calvet has received grants for research, fees for advisory boards, and lectures from Abott and MSD; S. García-López has received grants for assistance to scientific meetings from Abbott, MSD. He has also received consultancy fees from Abbott and MSD; C. Taxonera has served as speaker, consultant, and advisory for Abbott, MSD, and Shire; M. Barreiro-de Acosta has served as a consultant and an advisory board member for MSD and Abbott; M. Esteve has served as an advisory board for Abbott and MSD. The remaining authors declare no conflict of interest.

© The American College of Gastroenterology 2017. All Rights Reserved.
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