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P439 Effectiveness and safety of the sequential use of a second and third anti-TNF agent in patients with inflammatory bowel disease: results from the ENEIDA registry

M. J. Casanova*1, M. Chaparro1, M. Mínguez2, E. Ricart3, C. Taxonera4, S. García-López5, J. Guardiola6, A. López-San Román7, E. Iglesias8, B. Beltrán9, B. Sicilia10, M. I. Vera11, J. Hinojosa12, S. Riestra13, E. Domènech14, X. Calvet15, J. L. Pérez-Calle16, M. D. Martín-Arranz17, X. Aldeguer18, M. Rivero19, D. Monfort20, J. Barrio21, M. Esteve22, L. Márquez23, R. Lorente24, E. García-Planella25, L. de Castro26, F. Bermejo27, O. Merino28, A. Rodríguez-Pérez29, P. Martínez-Montiel30, M. Van Domselaar31, G. Alcaín32, M. Domínguez-Cajal33, C. Muñoz34, F. Gomollón35, L. Fernández-Salazar36, M. F. García-Sepulcre37, I. Rodríguez-Lago38, A. Gutiérrez39, F. Argüelles-Arias40, C. Rodriguez41, G. E. Rodríguez42, L. Bujanda43, J. Llaó44, P. Varela45, L. Ramos46, J. M. Huguet47, P. Almela48, P. Romero49, M. Navarro-Llavat, Á. Abad, P. Ramírez-de la Piscina, A. J. Lucendo, E. Sesé, R. E. Madrigal, M. Charro, A. García-Herola, R. Pajares, S. Khorrami, J. P. Gisbert1

1Hospital Universitario de La Princesa, IIS-IP , Universidad Autónoma de Madrid and CIBEREHD, Gastroenterology Unit, Madrid, Spain, 2Hospital Clínico Universitario de Valencia, Gastroenterology Unit, Valencia, Spain, 3Hospital Clínic i Provincial, CIBEREHD and IDIBAPS, Gastroenterology Unit, Barcelona, Spain, 4Hospital Universitario Clínico San Carlos, Gastroenterology Unit, Madrid, Spain, 5Hospital Universitario Miguel Servet and CIBEREHD, Gastroenterology Unit, Zaragoza, Spain, 6Hospital Universitario de Bellvitge, Gastroenterology Unit, Barcelona, Spain, 7Hospital Universitario Ramón y Cajal, Gastroenterology Unit, Madrid, Spain, 8Hospital Universitario Reina Sofía, Gastroenterology Unit, Córdoba, Spain, 9Hospital Universitario y Politécnico La Fe and CIBEREHD, Gastroenterology Unit, Valencia, Spain, 10Hospital Universitario de Burgos, Gastroenterology Unit, Burgos, Spain, 11Hospital Universitario Puerta de Hierro Majadahonda, Gastroenterology Unit, Madrid, Spain, 12Hospital de Manises, Gastroenterology Unit, Valencia, Spain, 13Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain, 14Hospital Universitario Germans Trias i Pujol and CIBEREHD, Gastroenterology Unit, Badalona, Spain, 15Hospital de Sabadell. Corporació Sanitària Universitària Parc Taulí and CIBEREHD, Gastroenterology Unit, Sabadell, Spain, 16Hospital Universitario Fundación de Alcorcón, Gastroenterology Unit, Madrid, Spain, 17Hospital Universitario La Paz and Instituto de Investigación de La Paz (IdiPaz), Gastroenterology Unit, Madrid, Spain, 18Hospital Universitari de Girona Dr. Josep Trueta, Gastroenterology Unit, Gerona, Spain, 19Hospital Universitario Marqués de Valdecilla and IDIVAL, Gastroenterology, Santander, Spain, 20Consorci Sanitari Terrassa, Gastroenterology, Tarrasa, Spain, 21Hospital Universitario Río Hortega, Gastroenterology, Valladolid, Spain, 22Hospital Universitario Mutua Terrasa, Gastroenterology Unit, Tarrasa, Spain, 23Hospital del Mar, Gastroenterology Unit, Barcelona, Spain, 24Hospital General Universitario de Ciudad Real and CIBEREHD, Gastroenterology Unit, Ciudad Real, Spain, 25Hospital de la Santa Creu i Sant Pau, Gastroenterology Unit, Barcelona, Spain, 26Complejo Hospitalario Universitario de Vigo, Gastroenterology Unit, Vigo, Spain, 27Hospital Universitario de Fuenlabrada and Instituto de Investigación de La Paz (IdiPaz), Gastroenterology Unit, Madrid, Spain, 28Hospital Universitario Cruces, Baracaldo, Spain, 29Hospital Clínico Universitario de Salamanca, Gastroenterology Unit, Salamanca, Spain, 30Hospital Universitario Doce de Octubre, Gastroenterology Unit, Madrid, Spain, 31Hospital de Torrejón, Gastroenterology Unit, Madrid, Spain, 32Hospital Universitario Virgen de la Victoria, Gastroenterology Unit, Málaga, Spain, 33Hospital General San Jorge, Gastroenterology Unit, Huesca, Spain, 34Hospital de Basurto, Gastroenterology Unit, Bilbao, Spain, 35Hospital Clínico Universitario Lozano Blesa, Gastroenteroogy Unit, Zaragoza, Spain, 36Hospital Clínico Universitario de Valladolid, Gastroenterology Unit, Valladolid, Spain, 37Hospital General Universitario de Elche, Gastroenterology Unit, Elche, Spain, 38Hospital de Galdakao-Usansolo, Gastroenterology Unit, Galdakao, Spain, 39Hospital General Universitario de Alicante and CIBEREHD, Gastroenterology Unit, Alicante, Spain, 40Hospital Universitario Virgen Macarena, Gastroenterology Unit, Sevilla, Spain, 41Complejo Hospitalario de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Gastroenterology Unit, Pamplona, Spain, 42Hospital Universitario Nuestra Señora de la Candelaria, Gastroenterology Unit, Santa Cruz de Tenerife, Spain, 43Hospital Universitario de Donostia, Instituto Biodonostia, Universidad del País Vasco (UPV/EHU) and CIBEREHD, Gastroenterology Unit, San Sebastián, Spain, 44ALTHAIA Xarxa Assistencial Universitària de Manresa, Gastroenterology Unit, Manresa, Spain, 45Hospital Universitario de Cabueñes, Gastroenterology Unit, Gijón, Spain, 46Hospital Universitario de Canarias, Gastroenterology Unit, La Laguna, Spain, 47Consorcio Hospital General Universitario de Valencia, Gastroenterology Unit, Valencia, Spain, 48Hospital General Universitario de Castellón, Gastroenterology Unit, Castellón, Spain, 49Hospital General Universitario de Santa Lucía, Gastroenterology Unit, Murcia, Spain, Hospital de Sant Joan Despí Moisès Broggi, Gastroenterology Unit, Sant Joan Despí, Spain, Hospital de Viladecans, Gastroenterology Unit, Barcelona, Spain, Hospital Universitario de Álava, Gastroenterology Unit, Vitoria, Spain, Hospital General de Tomelloso, Gastroenterology Unit, Ciudad Real, Spain, Hospital Universitario Arnau de Vilanova, Gastroenterology Unit, Lérida, Spain, Complejo Asistencial Universitario de Palencia, Gastroenterology Unit, Palencia, Spain, Hospital Royo Villanova, Gastroenterology Unit, Zaragoza, Spain, Hospital Marina Baixa, Gastroenterology Unit, Alicante, Spain, Hospital Universitario Infanta Sofía, Gastroenterology Unit, Madrid, Spain, Hospital Universitario Son Espases, Gastroenterology Unit, Palma de Mallorca, Spain


The aim of the present study was to investigate the efficacy and safety of the sequential use of a second and a third anti-TNF agent after failing or developing intolerance to an anti-TNF drug.


Patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) from ENEIDA registry (a prospectively maintained registry from GETECCU) who switched to another anti-TNF drug after failure or intolerance to a previous anti-TNF, were included. Efficacy, loss of response, and safety of the second and third anti-TNF were evaluated by logistic regression, Kaplan–Meier and Cox regression analyses.


In total, 1122 patients that switched to a second anti-TNF were included (50% men, mean age at diagnosis 31 years, 73% CD). The reasons for withdrawal the first anti-TNF were: primary failure (22%), secondary failure (51%), and intolerance (27%). Remission was achieved with the second anti-TNF drug in 45% of patients in the short-term. The rate of remission was similar between CD and UC patients (46% vs. 41%, p = 0.06). There was no difference in remission rates according to the sequence of the anti-TNF administration: infliximab–adalimumab or adalimumab–infliximab (42% vs. 48%, p = 0.07). The factors associated with a lower probability of achieving remission after a second anti-TNF were: combo therapy (OR = 0.5 95% CI = 0.4–0.8), to withdraw the first anti-TNF due to a primary failure (vs. intolerance; OR = 0.6, 95% CI = 0.4–0.9), and to withdraw the first anti-TNF due to secondary failure (vs. intolerance) (OR 0.6, 95% CI = 0.5–0.9). The cumulative incidence of loss of response after achieving remission with the second anti-TNF (median follow-up of 19 months) was 45%: 23% at 1 year and 62% at 5 years. The incidence of loss of response to the second anti-TNF was 19% per patient-year of follow-up. The factors associated with a higher risk of loss of response were: UC vs. CD (HR = 1.6; 95% CI = 1.1–2.1, p = 0.005) and combo therapy (HR = 2.4; 95% CI = 1.8–3, p < 0.0001). Adverse events occurred in 15% of the patients who switched to a second anti-TNF (10% stopped the treatment). Seventy-one patients switched to a third anti-TNF and 55% achieved remission. The incidence of loss of response to a third anti-TNF was 22% per patient-year (median follow-up of 9 months). Seven patients (11%) had adverse events, but only one discontinued the therapy.


Almost half of the patients who switched to a second anti-TNF achieved remission; however, a high proportion of them subsequently lost response. Factors associated with loss of response were type of inflammatory bowel disease and combo therapy. Approximately 50% of patients who received a third anti-TNF achieved remission; however, again, a high proportion of them lost response subsequently.