Casanova MJ¹, Chaparro M¹, Mínguez M², Ricart E³, Taxonera C⁴, García-López S⁵, Guardiola J⁶, López-San Román A⁷, Iglesias E⁸, Beltrán B⁹, Sicilia B¹⁰, Vera MI¹¹, Hinojosa J¹², Riestra S¹³, Domènech E¹⁴, Calvet X¹⁵, Pérez-Calle JL¹⁶, Martín-Arranz MD¹⁷, Aldeguer X¹⁸, Rivero M¹⁹, Monfort D²⁰, Barrio J²¹, Esteve M²², Márquez L²³, Lorente R²⁴, García-Planella E²⁵, de Castro L²⁶, Bermejo F²⁷, Merino O²⁸, Rodríguez-Pérez A²⁹, Martínez-Montiel P³⁰, Van Domselaar M³¹, Alcaín G³², Domínguez-Cajal M³³, Muñoz C³⁴, Gomollón F³⁵, Fernández-Salazar L³⁶, García-Sepulcre MF³⁷, Rodríguez-Lago I³⁸, Gutiérrez A³⁹, Argüelles-Arias F⁴⁰, Rodriguez C⁴¹, Rodríguez GE⁴², Bujanda L⁴³, Llaó J⁴⁴, Varela P⁴⁵, Ramos L⁴⁶, Huguet JM⁴⁷, Almela P⁴⁸, Romero P⁴⁹, Navarro-Llavat M⁵⁰, Abad Á⁵¹, Ramírez-de la Piscina P⁵², Lucendo AJ⁵³, Sesé E⁵⁴, Madrigal RE⁵⁵, Charro M⁵⁶, García-Herola A⁵⁷, Pajares R⁵⁸, Khorrami S⁵⁹, Gisbert JP¹. Inflamm Bowel Dis. 2019 Aug 29. pii: izz192. doi: 10.1093/ibd/izz192. [Epub ahead of print]

Author information

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

2 Gastroenterology Department at Hospital Clínico Valencia, Valencia, Spain.

3 Gastroenterology Department at Hospital Clínic i Provincial, CIBEREHD and IDIBAPS, Barcelona, Spain.

4 Gastroenterology Department at Hospital Universitario Clínico San Carlos, Madrid, Spain.

5 Gastroenterology Department at Hospital Universitario Miguel Servet, Barcelona, Spain; and CIBEREHD, Zaragoza, Spain.

6 Gastroenterology Department at Hospital Universitario de Bellvitge, Barcelona, Spain.

7 Gastroenterology Department at Hospital Universitario Ramón y Cajal, Madrid, Spain.

8 Gastroenterology Department at Hospital Universitario Reina Sofía, Córdoba, Spain.

9 Gastroenterology Department at Hospital Universitario La Fe, and CIBEREHD, Valencia, Spain.

10 Gastroenterology Department at Hospital Universitario de Burgos, Burgos, Spain.

11 Gastroenterology Department at Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.

12 Gastroenterology Department at Hospital de Manises, Valencia, Spain.

13 Gastroenterology Department at Hospital Universitario Central de Asturias, Oviedo, Spain.

14 Gastroenterology Department at Hospital Universitario Germans Trias i Pujol, and CIBEREHD, Badalona, Spain.

15 Gastroenterology Department at Hospital de Sabadell, Corporació Sanitària Universitària Parc Taulí, and CIBEREHD, Sabadell, Spain.

16 Gastroenterology Department at Hospital Universitario Fundación de Alcorcón, Madrid, Spain.

17 Gastroenterology Department at Hospital Universitario La Paz,, Girona, Spain; Instituto de Investigación de La Paz (IdiPaz), Madrid, Spain.

18 Gastroenterology Department at Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain.

19 Gastroenterology Department at Hospital Universitario Marqués de Valdecilla,, Terrassa, Spain; IDIVAL, Santander, Spain.

20 Gastroenterology Department at Consorci Sanitari Terrassa, Terrassa, Spain.

21 Gastroenterology Department at Hospital Universitario Río Hortega, Valladolid, Spain.

22 Gastroenterology Department at Hospital Universitario Mútua Terrassa, and CIBEREHD, Terrassa, Spain.

23 Gastroenterology Department at Hospital del Mar, Barcelona, Spain.

24 Gastroenterology Department at Hospital General Universitario de Ciudad Real, Ciudad Real, Spain.

25 Gastroenterology Department at Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.

26 Gastroenterology Department at Complejo Hospitalario Universitario de Vigo, Vigo, Spain.

27 Gastroenterology Department at Hospital Universitario de Fuenlabrada and Instituto de Investigación de La Paz (IdiPaz), Madrid, Spain.

28 Gastroenterology Department at Hospital Universitario Cruces, Barakaldo, Spain.

29 Gastroenterology Department at Hospital Clínico Universitario de Salamanca, Salamanca.

30 Gastroenterology Department at Hospital Universitario Doce de Octubre, Madrid, Spain.

31 Gastroenterology Department at Hospital de Torrejón, Madrid.

32 Gastroenterology Department at Hospital Universitario Virgen de la Victoria, Málaga, Spain.

33 Gastroenterology Department at Hospital General San Jorge, Huesca, Spain.

34 Gastroenterology Department at Hospital de Basurto, Bilbao, Spain.

35 Gastroenterology Department at Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain.

36 Gastroenterology Department at Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

37 Gastroenterology Department at Hospital General Universitario de Elche, Alicante, Spain.

38 Gastroenterology Department at Hospital de Galdakao-Usansolo, Galdakao, Spain.

39 Gastroenterology Department at Hospital General Universitario de Alicante, and CIBEREHD, Alicante, Spain.

40 Gastroenterology Department at Hospital Universitario Virgen Macarena, Sevilla, Spain.

41 Gastroenterology Department at Complejo Hospitalario de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.

42 Gastroenterology Department at Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain.

43 Gastroenterology Department at Hospital Universitario de Donostia, Instituto Biodonostia, Universidad del País Vasco (UPV/EHU), and CIBEREHD, Donostia, Spain.

44 Gastroenterology Department at ALTHAIA Xarxa Assistencial Universitària de Manresa, Manresa, Spain.

45 Gastroenterology Department at Hospital Universitario de Cabueñes, Gijón, Spain.

46 Gastroenterology Department at Hospital Universitario de Canarias, La Laguna, Spain.

47 Gastroenterology Department at Consorcio Hospital General Universitario de Valencia, Valencia, Spain.

48 Gastroenterology Department at Hospital General Universitario de Castellón, Castellón, Spain.

49 Gastroenterology Department at Hospital General Universitario de Santa Lucía, Murcia, Spain.

50 Gastroenterology Department at Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain.

51 Gastroenterology Department at Hospital de Viladecans, Barcelona, Spain.

52 Gastroenterology Department at Hospital Universitario de Álava, Vitoria, Spain.

53 Gastroenterology Department at Hospital General de Tomelloso, Ciudad Real, Spain.

54 Gastroenterology Department at Hospital Universitario Arnau de Vilanova, Lleida, Spain.

55 Gastroenterology Department at Complejo Asistencial Universitario de Palencia, Palencia, Spain.

56 Gastroenterology Department at Hospital Royo Villanova, Zaragoza, Spain.

57 Gastroenterology Department at Hospital Marina Baixa, Alicante, Spain.

58 Gastroenterology Department at Hospital Universitario Infanta Sofía, Madrid, Spain.

59 Gastroenterology Department at Hospital Universitario Son Espases, Palma de Mallorca, Spain.

Abstract

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients.

METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent.

RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug.

CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.