Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial
Authors: Chaparro María , Donday María G. , Barreiro-de Acosta Manuel , Domènech Eugeni , Esteve María , García-Sánchez Valle , Nos Pilar , Panés Julián , Martínez Concepción , Gisbert Javier P. , Abad F. , Aguas Peris M. , Agüero Tejado E. , Alba C. , Albert M. , Alemán H. , Algaba A. , Alonso Abreu I. , Amador M.P. , Amat M. , Angueira T. , Arajol C. , Arias-González L. , Arrondo Velasco A. , Baldán M. , Bardán García B. , Bargalló García A. , Barreiro de Acosta M. , Barrio Andrés J. , Bastida Paz G. , Bastón Rey I. , Batista L. , Bellver Martínez M. , Beltrán Niclós B. , Benítez J.M. , Ber Nieto Y. , Bermejo F. , Bernardo D. , Blázquez Gómez I. , Bouhmidi Assakali A. , Busquets Casals D. , Cabriada Nuño J.L. , Calvet Calvo X. , Calvo Hernández M.V. , Calvo M. , Camps B. , Carbajo A.Y. , Cardona Peitx G. , Caro-Patón T. , Carrillo Palau M. , Carrión Bolorino S. , Casanova M.J. , Casellas Valdé J.A. , Castaño García A. , Castro Senosiain B. , Ceballos D. , Cerrillo E. , Chacón Martínez S. , Consuelo Cañete Pizarro F. , de Castro Parga M.L. , de Miguel M. , de Francisco García R. , de la Cruz Ramírez M.D. , del Hoyo Francisco J. , Delgado Guillena P. , Desongles Corrales T. , Echarri Piudo A. , Espino Paisan E. , Espona Quer M. , Fernández Pordomingo A. , Fernández Forcelledo J.L. , Fernández-Tomé S. , Ferreiro Iglesias R. , Ferrer Bradley I. , Ferrer A. , Figueroa A. , Gallach Montero M. , García Iglesias P. , García García-Lezcún C. , García Ramírez L. , García García M.J. , García-Bosh O. , Garre A. , Giménez Poderós T. , Gómez Irwin L. , Gómez Pastrana B. , Gómez Delgado E. , González Lama Y. , Gracia García Á. , Gracia García B. , Guardiola J. , Guerra I. , Guerra E. , Guillot V. , Gustmancher Saiz S. , Gutiérrez Casbas A. , Hernández Ramírez V. , Hernando Verdugo M.M. , Hernández Muniesa B. , Hernanz Chaves R. , Herrera Justiniano J.M. , Hinojosa del Val J , Ibáñez Feijoo S , Iborra Colomino M , Iglesias Flores E , Izquierdo García E. , Sampedro González M J , Lucendo A J. , Jiménez García N , Leo Carnerero E. , Loizaga Díaz I. , López de Torre Querejazu A , López Sánchez P , Luis Parras J , Maia Boscá M , Mañosa M , Marín Pedrosa S , Marín A , Marinero Á , Marín-Jiménez I , Márquez Mosquera L , Márquez Galán JL , Martín Arranz E , Martín Arranz MD , Martínez Cadilla J , Martínez Sesmero JM , Martínez Sánchez B , Matallana V , Mateos Hernández MI , McNicholl AG , Mejuto Fernández R , Melcarne L , Menchén L , Méndez-Castrillón Rodríguez J , Merino Ochoa O , Mínguez M , Molas Ferrer G , Montoro Huguet M , Montserrat Torres A , Mora F , Moraleja Yudego I , Morales Alvarado VJ , Morales Martínez L , Morell A , Motos García C , Muñoz Alonso F , Muñoz Villafranca MC , Muñoz JE , Mur A , Nantes Ó , Navarro P , Navarro- Llavat M , Nos Mateu P , Núñez Alonso A , Núñez Ortiz A , Olivares D , Ollero Pena V , Orobitg J , Ortega L , Ortiz de Zárate J , Pallarés Manrique H , Paradela Carreiro A , Peral Ballester L , Pereira Bueno S , Pérez Martínez I , Pineda Mariño JR , Piñero Pérez C , Planas Giner A , Plaza Santos MR , Ponferrada Díaz Á , Poza Cardón J , Prieto Vicente V , Puchades L , Ramos López L , Redondo S , Riestra Menéndez S , Rivero Tirado M , Rodríguez Lago I , Rodríguez Gutiérrez C , Rodríguez E , Romero Izquierdo S , Rubio Iturria S , Ruiz Antorán MB , Ruiz A , Salazar LF , Sánchez Ulayar A , Sánchez Gómez E , Sánchez C , Sangrador C , Serra K , Spicakova K , Suárez Ferrer C , Talavera Fabuel A , Taxonera C , Tordera M , Torrella Cortés E , Tosca J , Trigo Salado C , Uriarte Estefanía F , Van Domselaar M , Vázquez Morón JM , Ventura López P , Vera M , Vicuña Arregui M , Villoria Ferrer A , Virgós Aller T , Yáñez Feria D 
Published: September 2019

Background:

Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment versus those who continue treatment.

Methods:

This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn’s disease or ulcerative colitis who have achieved clinical remission for ⩾6 months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1 year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal.

Results:

Enrolment began in 2016, and the study is expected to end in 2020.

Conclusions:

This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission.

Clinical trial reference number:

EudraCT 2015-001410-10