P386 Long-term evolution after anti-TNF discontinuation in patients with inflammatory bowel disease (IBD): A multicentre study

M.J. Casanova1, M. Chaparro2, O. Nantes3, J.M. Benítez4, M. Rojas-Feria5, J. Castro-Poceiro6, J.M. Huguet7, A. Martín-Cardona8, M. Aicart9, J. Tosca10, M.D.M. Martín-Rodríguez11, C. González-Muñoza12, M. Mañosa13, E. Leo-Carnerero14, L. Lamuela15, I. Pérez-Martínez16, L. Bujanda17, J. Hinojosa18, R. Pajares19, F. Argüelles-Arias20, J.L. Pérez-Calle21, G.E. Rodríguez-González22, J. Guardiola23, M. Barreiro-de Acosta24, F. Bermejo25, J. Barrio26, B. Beltrán27, F. Gomollón28, R. Lorente29, A. Gutierrez30, M. Domínguez-Cajal31, C. Dueñas32, A. Ponferrada-Díaz33, M. Van Domselaar34, P. Ramírez-de la Piscina35, L. Ramos36, P. Almela37, M. Navarro-Llavat38, B. Botella39, J.P. Gisbert2, EVODIS

1Gastroenterology Unit, Hospital Universitario de La Princesa-IIS-IP and CIBEREHD, Madrid, Spain, 2Gastroenterology Unit, Hospital Universitario de La Princesa- IIS-IP and CIBEREHD, Madrid, Spain, 3Gastroenterology Unit, Complejo Hospitalario de Navarra- Instituto de Investigación Sanitaria de Navarra IdiSNA, Pamplona, Spain, 4Gastroenterlogy Unit, Hospital Universitario Reina Sofía- Instituto Maimónides de Investigación Biomédica de Córdoba IMIBIC, Córdoba, Spain, 5Gastroenterology Unit, Hospital Universitario de Valme and CIBEREHD, Sevilla, Spain, 6Gastroenterology Unit, Hospital Clínic i Provincial and CIBEREHD, Barcelona, Spain, 7Gastroenterology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain, 8Gastroenterology Unit, Hospital Universitario Mutua Terrassa- and CIBEREHD, Terrassa, Spain, 9Gastroenterology Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain, 10Gastroenterology Unit, Hospital Clínico, Valencia, Spain, 11Gastroenterology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain, 12Gastroenterology Unit, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain, 13Gastroenterology Unit, Hospital Universitario Germans Trias i Pujol and CIBEREHD, Badalona, Spain, 14Gastroenterology Unit, Hospital Universitario Virgen del Rocío, Sevilla, Spain, 15Gastroenterology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain, 16Gastroenterology Unit, Hospital Universitario Central de Asturias, Oviedo, Spain, 17Gastroenterology Unit, Hospital Universitario de Donostia- Instituto Biodonostia- Universidad del País Vasco UPV/EHU- and CIBEREHD, Donostia, Spain, 18Gastroenterology Unit, Hospital de Manises, Valencia, Spain, 19Gastroenterology Unit, Hospital Universitario Infanta Sofía, Madrid, Spain, 20Gastroenterology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain, 21Gastroenterology Unit, Hospital Universitario Fundación de Alcorcón, Madrid, Spain, 22Gastroenterology Unit, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain, 23Gastroenterology Unit, Hospital Universitario de Bellvitge, Barcelona, Spain, 24Gastroenterology Unit, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain, 25Gastroenterology Unit, Hospital Universitario de Fuenlabrada- Instituto de Investigación Sanitaria del Hospital La Paz IdiPAZ, Madrid, Spain, 26Gastroenterology Unit, Hospital Universitario Río Hortega, Valladolid, Spain, 27Gastroenterology Unit, Hospital Universitario La Fe- and CIBEREHD, Valencia, Spain, 28Gastroenterology Unit, Hospital Clínico Lozano Blesa- Instituto de Investigación Sanitaria Aragón IIS Aragón- and CIBEREHD, Zaragoza, Spain, 29Gastroenterology Unit, Hospital General de Ciudad Real, Ciudad Real, Spain, 30Gastroenterology Unit, Hospital General Universitario de Alicante- and CIBEREHD, Alicantesp, Spain, 31Gastroenterology Unit, Hospital General San Jorge, Huesca, Spain, 32Gastroenterology Unit, Hospital Universitario de Cáceres, Cáceres, Spain, 33Gastroenterology Unit, Hospital Universitario Infanta Leonor, Madrid, Spain, 34Gastroenterology Unit, Hospital de Torrejón de Ardoz, Madrid, Spain, 35Gastroenterology Unit, Hospital HUA Álava, Vitoria, Spain, 36Gastroenterology Unit, Hospital Universitario de Canarias, La Laguna, Spain, 37Gastroenterology Unit, Hospital General Universitario de Castellón, Castellón, Spain, 38Gastroenterology Unit, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain, 39Gastroenterology Unit, Hospital Universitario Infanta Cristina, Madrid, Spain

Background

(1) To assess the risk of relapse at long-term after anti-TNF discontinuation, (2) to identify the factors associated with relapse, (3) to calculate the response rate to re-treatment with the same anti-TNF, (4) to evaluate the safety of re-treatment with these drugs, and (5) to investigate the rate of complications of patients that relapsed.

Methods

A retrospective, observational, multicentre study conducted at 39 Spanish centres. Crohn’s disease or ulcerative colitis patients who had been treated with anti-TNFs and in whom these drugs had been withdrawn after achieving clinical remission, were included. Follow-up time after anti-TNF discontinuation was at least 6 months.

Results

Six hundred and thirty-seven patients were included (53% women, mean age 42, 68% Crohn’s disease). The reasons for discontinuation were: 74% elective decision, 19% adverse events, and 7% remission after top-down strategy. The median follow-up time was 60 months. In patients who relapsed, the median time to relapse after anti-TNF discontinuation was 24 months. The cumulative incidence of relapse was 54% (50–58%): 17% at 1 year, 28% at 2, 34% at 3, and 45% at 5 years after anti-TNF withdrawal. The incidence rate of relapse was 11% per patient-year (10–12%). At the time of anti-TNF discontinuation, endoscopy was performed in 48% of patients; of these, 88% had a normal endoscopy and 9% had mild activity. 68% of patients maintained immunomodulators (IMMs) after discontinuing the anti-TNF. In the multivariate analysis, older age at diagnosis (HR = 0.99; 95% CI = 0.98–0.99, p = 0.003) and the maintenance of IMMs after anti-TNF discontinuation (HR = 0.53; 95% CI = 0.42–0.66, p < 0.0001) were associated with a lower risk of relapse. After relapse, 49% of patients were re-treated with the same anti-TNF, 47% received another drug, and 4% were operated on. Of patients who restarted the same anti-TNF, 79% (70–86%) achieved remission. After re-treatment, 11% presented adverse events, all mild. Of the 48 patients who did not respond after anti-TNF re-treatment, 41% (26–57%) achieved remission with other therapies, and 21% of these patients relapsed at the end of follow-up. Of the 161 patients who started other treatment after relapse, 62% (54–70%) achieved remission with the new treatment, and 30% of these patients relapsed.

Conclusion

The incidence rate of relapse after anti-TNF discontinuation in IBD Patients who were in remission was 11% per patient-year, and 45% relapsed at 5 years. Older age at diagnosis and maintenance treatment with IMMs were associated with a lower risk of relapse. Re-treatment of relapse with the same anti-TNF was effective and safe. Less than half of the patients who did not respond after re-treatment achieved remission with other therapies.