P500 Evolution after anti-TNF drug discontinuation in patients with inflammatory bowel disease (IBD): a multicenter long-term follow-up study.
M.J. Casanova*1, M. Chaparro1, V. García-Sánchez2, O. Nantes3, A. Jáuregui-Amezaga4, M. Rojas-Feria5, J.R. Pineda6, J. Tosca7, M.P. Martínez-Montiel8, L. Luzón9, R. Pajares10, B. Beltrán11, M. Barreiro de-Acosta12, L. Ramos13, I. Pérez-Martínez14, F. Bermejo15, Y. González-Lama16, M. Domínguez-Cajal17, J.M. Huguet18, B. Sicilia19, C. Dueñas-Sadornil20, A. Ponferrada-Díaz21, O. Merino22, X. Calvet23, M. Menacho24, J. Guardiola25, P. Ramírez de la Piscina26, J.L. Pérez-Calle27, M. Domínguez-Antonaya28, M. Piqueras29, L. Fernández-Salazar30, D. Busquets31, J.M. Benítez-Cantero2, C. Rodriguez3, J.P. Gisbert1
1Hospital Universitario de La Princesa, IIS-IP and CIBERehd, Gastroenterology Unit, Madrid, Spain, 2Hospital Universitario Reina Sofía, Gastroenterology Unit, Córdoba, Spain, 3Complejo Hospitalario de Navarra, Gastroenterology Unit, Pamplona, Spain, 4Hospital Clinic de Barcelona and CIBERehd, Gastroenterology Unit, Barcelona, Spain, 5Hospital de Valme and CIBERehd, Gastroenterology Unit, Sevilla, Spain, 6Complejo Hospitalario Universitario de Vigo, Gastroenterology Unit, Vigo, Spain, 7Hospital Clínico Universitario, Gastroenterology Unit, Valencia, Spain, 8Hospital Universitario 12 de Octubre, Gastroenterology Unit, Madrid, Spain, 9Hospital Universitario Miguel Servet, Gastroenterology Unit, Zaragoza, Spain, 10Hospital Infanta Sofía, Gastroenterology Unit, Madrid, Spain, 11Hospital Universitario La Fe and CIBERehd, Gastroenterology Unit, Valencia, Spain, 12Complejo Hospitalario Universitario de Santiago, Gastroenterology Unit, Santiago de Compostela, Spain, 13Hospital Universitario de Canarias, Gastroenterology Unit, SantaCruz de Tenerife, Spain, 14Hospital Universitario Central de Asturias, Gastroenterology Unit, Oviedo, Spain, 15Hospital Universitario de Fuenlabrada, Gastroenterology Unit, Madrid, Spain, 16Hospital Puerta de Hierro, Gastroenterology Unit, Madrid, Spain, 17Hospital General San Jorge, Gastroenterology Unit, Huesca, Spain, 18Consorcio Hospital General Universitario de Valencia, Gastroenterology Unit, Valencia, Spain, 19Hospital Universitario de Burgos, Gastroenterology unit, Burgos, Spain, 20Hospital San Pedro de Alcántara, Gastroenterology Unit, Cáceres, Spain, 21Hospital Infanta Leonor, Gastroenterology Unit, Madrid, Spain, 22Hospital Universitario de Cruces, Gastroenterology Unit, Bilbao, Spain, 23Hospital de Sabadell. Corporació Sanitària Universitària Parc Taulí and CIBERehd, Gastroenterology Unit, Sabadell, Spain, 24Hospital Joan XXIII, Gastroenterology Unit, Tarragona, Spain, 25Hospital de Bellvitge, Gastroenterology unit, Barcelona, Spain, 26Hospital Universitario de Alava, Gastroenterology Unit, Vitoria, Spain, 27Hospital Universitario Fundación Alcorcón, Gastroenterology Unit, Madrid, Spain, 28Hospital Universitario de Móstoles, Gastroenterology Unit, Madrid, Spain, 29Hospital Universitari Mutua de Terrasa, Gastroenterology Unit, Barcelona, Spain, 30Hospital Clínico Universitario de Valladolid, Gastroenterology Unit, Valladolid, Spain, 31Hospital universitari de Girona Dr Josep Trueta, Gastroenterology Unit, Girona, Spain
The discontinuation of anti-TNF treatment after achieving remission in IBD patients could be considered due to safety and cost issues.
Aims: 1) to assess the risk of relapse 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, and 4) to evaluate the safety of re-treatment with these drugs
Retrospective, observational, multicenter study conducted at 90 Spanish centers. 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. Long-term maintenance of remission was estimated using Kaplan-Meier curves. Cox-regression analysis was performed to identify predictive factors for relapse.
At present, 311 patients have been included (53% women, mean age 42 y, 68% Crohn's disease). The reasons for anti-TNF discontinuation were: 62% medical decision, 21% adverse events, 12% patient desire, and 5% remission after top-down strategy. The median follow-up time was 24 months. The median time to relapse after anti-TNF discontinuation was 15 months, and the cumulative incidence of relapse was 37% (95%CI=32-43%): 4% at 6 months, 24% at 1 year, 37% at 2 years, 40% at 3 years, and 53% at 5 years after anti-TNF withdrawal. The incidence rate of relapse was 19% per patient-year (15-22%). At the time of anti-TNF discontinuation, endoscopy was performed in 49% of patients; of these, 88% had a normal endoscopy and 12% had mild activity. 66% of patients continued with an immunomodulator (IMM; AZA/MP/MTX) after discontinuing the anti-TNF. In the univariate analysis, the variables associated with a higher relapse risk were: female gender (p<0.02) and lack of maintenance of an IMM after anti-TNF discontinuation (p<0.01). In the multivariate analysis, the only variable associated with the risk of relapse was the treatment with IMMs after anti-TNF discontinuation (lower risk; HR=0.5, 95%CI=0.3-0.7). The incidence rate of relapse when an IMM was prescribed was 15% per patient-year. 72% of patients who relapsed were re-treated with the same anti-TNF; 68% of them achieved remission after induction, and 80% at the end of follow-up; 4 patients (5%) presented adverse events, all mild.
The incidence rate of relapse after anti-TNF drug discontinuation in IBD patients that were in remission was 19% per patient-year. The only predictive factor for relapse was the lack of IMM maintenance treatment after anti-TNF is stopped. Re-treatment of relapse with the same anti-TNF was effective (80% remission) and safe.