GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )

Summary

This study will be a multicentre prospective randomized trial to assess the percentage of patients with IBD who, after stopping anti-TNF treatment, have sustained clinical remission at one year compared to those in which the treatment is continued at stable doses

Timeline

Start

2017-04-21

Primary completion

2021-12-31

Completion

2022-12-31

Publications

• Background Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology. 2005 Apr;128(4):862-9. doi: 10.1053/j.gastro.2005.01.048.
• Background Clarke K, Regueiro M. Stopping immunomodulators and biologics in inflammatory bowel disease patients in remission. Inflamm Bowel Dis. 2012 Jan;18(1):174-9. doi: 10.1002/ibd.21792. Epub 2011 Jun 14.
• Background Louis E, Belaiche J, Reenaers C. Anti-TNF and Crohn's disease: when should we stop? Curr Drug Targets. 2010 Feb;11(2):148-51. doi: 10.2174/138945010790309957.
• Background Pariente B, Laharie D. Review article: why, when and how to de-escalate therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2014 Aug;40(4):338-53. doi: 10.1111/apt.12838. Epub 2014 Jun 23.
• Background Sorrentino D, Nash P, Viladomiu M, Hontecillas R, Bassaganya-Riera J. Stopping anti-TNF agents in patients with Crohn's disease in remission: is it a feasible long-term strategy? Inflamm Bowel Dis. 2014 Apr;20(4):757-66. doi: 10.1097/01.MIB.0000442680.47427.bf. No abstract available.
• Background Solberg IC, Vatn MH, Hoie O, Stray N, Sauar J, Jahnsen J, Moum B, Lygren I; IBSEN Study Group. Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol. 2007 Dec;5(12):1430-8. doi: 10.1016/j.cgh.2007.09.002.
• Background Steenholdt C, Molazahi A, Ainsworth MA, Brynskov J, Ostergaard Thomsen O, Seidelin JB. Outcome after discontinuation of infliximab in patients with inflammatory bowel disease in clinical remission: an observational Danish single center study. Scand J Gastroenterol. 2012 May;47(5):518-27. doi: 10.3109/00365521.2012.660541. Epub 2012 Mar 1.
• Background Gisbert JP, Marin AC, Chaparro M. The Risk of Relapse after Anti-TNF Discontinuation in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. Am J Gastroenterol. 2016 May;111(5):632-47. doi: 10.1038/ajg.2016.54. Epub 2016 Mar 22.
• Background Regueiro M, Kip KE, Baidoo L, Swoger JM, Schraut W. Postoperative therapy with infliximab prevents long-term Crohn's disease recurrence. Clin Gastroenterol Hepatol. 2014 Sep;12(9):1494-502.e1. doi: 10.1016/j.cgh.2013.12.035. Epub 2014 Jan 16.
• Background Bortlík M, Ďuricová D, Lukáš M, Malíčková K, Machková N, Hrdlička L, et al. Infliximab trough levels at treatment discontinuation are associated with increased risk of disease relapse in patients with inflammatory bowel diseases. 20th United European Gastroenterology Week. 2012:P0870.
• Background Guidi L, Ratto C, Semeraro S, Roberto I, De Vitis I, Papa A, Marzo M, Parello A, Foglietto G, Doglietto GB, Gasbarrini GB, Fedeli G. Combined therapy with infliximab and seton drainage for perianal fistulizing Crohn's disease with anal endosonographic monitoring: a single-centre experience. Tech Coloproctol. 2008 Jun;12(2):111-7. doi: 10.1007/s10151-008-0411-0. Epub 2008 Jun 10.
• Background Domenech E, Hinojosa J, Nos P, Garcia-Planella E, Cabre E, Bernal I, Gassull MA. Clinical evolution of luminal and perianal Crohn's disease after inducing remission with infliximab: how long should patients be treated? Aliment Pharmacol Ther. 2005 Dec;22(11-12):1107-13. doi: 10.1111/j.1365-2036.2005.02670.x.
• Background Wynands J, Belbouab R, Candon S, Talbotec C, Mougenot JF, Chatenoud L, Schmitz J, Cezard JP, Goulet O, Hugot JP, Ruemmele FM. 12-month follow-up after successful infliximab therapy in pediatric crohn disease. J Pediatr Gastroenterol Nutr. 2008 Mar;46(3):293-8. doi: 10.1097/MPG.0b013e31815604cd.
• Background Dart RJ, Griffin N, Taylor K, Duncan J, Sastrillo M, Sanderson J, Irving PM. Reassessment of Crohn's disease treated with at least 12 months of anti-TNF therapy: how likely is treatment withdrawal? Frontline Gastroenterol. 2014 Jul;5(3):176-182. doi: 10.1136/flgastro-2013-100392. Epub 2013 Dec 24.
• Background Louis E, Mary JY, Vernier-Massouille G, Grimaud JC, Bouhnik Y, Laharie D, Dupas JL, Pillant H, Picon L, Veyrac M, Flamant M, Savoye G, Jian R, Devos M, Porcher R, Paintaud G, Piver E, Colombel JF, Lemann M; Groupe D'etudes Therapeutiques Des Affections Inflammatoires Digestives. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology. 2012 Jan;142(1):63-70.e5; quiz e31. doi: 10.1053/j.gastro.2011.09.034. Epub 2011 Sep 22.
• Background Lu C, Waugh A, Bailey RJ, Cherry R, Dieleman LA, Gramlich L, Matic K, Millan M, Kroeker KI, Sadowski D, Teshima CW, Todoruk D, Wong C, Wong K, Fedorak RN. Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation. World J Gastroenterol. 2012 Sep 28;18(36):5058-64. doi: 10.3748/wjg.v18.i36.5058.
• Background Molnar T, Lakatos PL, Farkas K, Nagy F, Szepes Z, Miheller P, Horvath G, Papp M, Palatka K, Nyari T, Balint A, Lorinczy K, Wittmann T. Predictors of relapse in patients with Crohn's disease in remission after 1 year of biological therapy. Aliment Pharmacol Ther. 2013 Jan;37(2):225-33. doi: 10.1111/apt.12160. Epub 2012 Nov 26.
• Background Molander P, Farkkila M, Salminen K, Kemppainen H, Blomster T, Koskela R, Jussila A, Rautiainen H, Nissinen M, Haapamaki J, Arkkila P, Nieminen U, Kuisma J, Punkkinen J, Kolho KL, Mustonen H, Sipponen T. Outcome after discontinuation of TNFalpha-blocking therapy in patients with inflammatory bowel disease in deep remission. Inflamm Bowel Dis. 2014 Jun;20(6):1021-8. doi: 10.1097/MIB.0000000000000052.
• Background Echarri A, Ollero V, Gallego C, Porta A, Castro J. Anti-TNF withdrawal in IBD patients on deep remission. Risk factors of relapse. 20th United European Gastroenterology Week. 2012:P0287.
• Background Caviglia R, Ribolsi M, Rizzi M, Emerenziani S, Annunziata M, Cicala M. Maintenance of remission with infliximab in inflammatory bowel disease: efficacy and safety long-term follow-up. World J Gastroenterol. 2007 Oct 21;13(39):5238-44. doi: 10.3748/wjg.v13.i39.5238.
• Background Ciria V, Silva P, Leo E, Trigo C, De la Cruz MD, Herrera JM, et al. Factors influencing recurrence following suspension of biological treatment. Importance of mucosal healing. J Crohns Colitis. 2014;8 (suppl.1):P487.
• Background Chauvin A, Le Thuaut A, Belhassan M, Le Baleur Y, Mesli F, Bastuji-Garin S, Delchier JC, Amiot A. Infliximab as a bridge to remission maintained by antimetabolite therapy in Crohn's disease: A retrospective study. Dig Liver Dis. 2014 Aug;46(8):695-700. doi: 10.1016/j.dld.2014.04.012. Epub 2014 Jun 2.
• Background Ramos L, Hernandez A, Carrillo M, Alonso I, Hernandez N, Quintero E. Outcome of treatment with biological agents in Crohn's disease: 117 patients in 5 years from a tertiary referral center. J Crohns Colitis. 2014;8 (suppl.1):P398.
• Background Luppino I, Spagnuolo R, Marasco R, Cosco C, Ruggiero G, Cosco V, et al. Withdrawal of infliximab (IFX) after achieving remission: outcome in a cohort of inflammatory bowel disease (IBD) patients. Dig Liver Dis. [Conference abstract: Abstracts of the 19th National Congress of Digestive Diseases]. 2013;45S:S100-S1.
• Background Marino M, Zucchi E, Fabbro M, Lodolo I, Maieron R, Vadalà S, et al. Outcome of infliximab discontinuation in IBD patients and therapy rechallenging in relapsers: Single centre preliminary data. J Crohns Colitis. 2014;8 (suppl.1):P401.
• Background Crombe V, Salleron J, Savoye G, Dupas JL, Vernier-Massouille G, Lerebours E, Cortot A, Merle V, Vasseur F, Turck D, Gower-Rousseau C, Lemann M, Colombel JF, Duhamel A. Long-term outcome of treatment with infliximab in pediatric-onset Crohn's disease: a population-based study. Inflamm Bowel Dis. 2011 Oct;17(10):2144-52. doi: 10.1002/ibd.21615. Epub 2011 Feb 1.
• Background Annunziata ML, Papparella LG, Sansoni I, Balestrieri P, Cicala M. Normalized wall thickness at MRE predicts clinical remission in Crohn's disease after infliximab discontinuation: a 5 years follow-up. J Crohns Colitis. 2014;8 (suppl.1):P402.
• Background Waugh AW, Garg S, Matic K, Gramlich L, Wong C, Sadowski DC, Millan M, Bailey R, Todoruk D, Cherry R, Teshima CW, Dieleman L, Fedorak RN. Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort. Aliment Pharmacol Ther. 2010 Nov;32(9):1129-34. doi: 10.1111/j.1365-2036.2010.04446.x. Epub 2010 Aug 30.
• Background Nuti F, Conte F, Cavallari N, Civitelli F, Aloi M, Alessandri C, et al. Long term efficacy of infliximab in inflammatory bowel disease at a single tertiary center. Dig Liver Dis. [Congress comunication: 17th National Congress SIGENP]. 2010;42(SUPPL. 5):S326-S7.
• Background Farkas K, Lakatos PL, Nagy F, Szepes Z, Miheller P, Papp M, Palatka K, Balint A, Bor R, Wittmann T, Molnar T. Predictors of relapse in patients with ulcerative colitis in remission after one-year of infliximab therapy. Scand J Gastroenterol. 2013 Dec;48(12):1394-8. doi: 10.3109/00365521.2013.845906. Epub 2013 Oct 16.
• Background Armuzzi A, Marzo M, Felice C, De Vincentis F, Andrisani G, Moccio G, et al. Long-term scheduled therapy with infliximab in inflammatory bowel disease: a single-centre observational study. Gastroenterology. 2010;238 (suppl.1):S-691.
• Background Muñoz C, Bravo MT, Ortiz de Zárate J, Arreba P, García I, Heras J, et al. Mucosal healing in patients with ulcerative colitis treated with infliximab. What happens after treatment is discontinued? J Crohns Colitis. 2014;8 (suppl.1):P405.
• Background Dai C, Liu WX, Jiang M, Sun MJ. Mucosal healing did not predict sustained clinical remission in patients with IBD after discontinuation of one-year infliximab therapy. PLoS One. 2014 Oct 20;9(10):e110797. doi: 10.1371/journal.pone.0110797. eCollection 2014.
• Background Casanova MJ, Chaparro M, Garcia-Sanchez V, Nantes O, Leo E, Rojas-Feria M, Jauregui-Amezaga A, Garcia-Lopez S, Huguet JM, Arguelles-Arias F, Aicart M, Marin-Jimenez I, Gomez-Garcia M, Munoz F, Esteve M, Bujanda L, Cortes X, Tosca J, Pineda JR, Manosa M, Llao J, Guardiola J, Perez-Martinez I, Munoz C, Gonzalez-Lama Y, Hinojosa J, Vazquez JM, Martinez-Montiel MP, Rodriguez GE, Pajares R, Garcia-Sepulcre MF, Hernandez-Martinez A, Perez-Calle JL, Beltran B, Busquets D, Ramos L, Bermejo F, Barrio J, Barreiro-de Acosta M, Roncedo O, Calvet X, Hervias D, Gomollon F, Dominguez-Antonaya M, Alcain G, Sicilia B, Duenas C, Gutierrez A, Lorente-Poyatos R, Dominguez M, Khorrami S, Munoz C, Taxonera C, Rodriguez-Perez A, Ponferrada A, Van Domselaar M, Arias-Rivera ML, Merino O, Castro E, Marrero JM, Martin-Arranz M, Botella B, Fernandez-Salazar L, Monfort D, Opio V, Garcia-Herola A, Menacho M, Ramirez-de la Piscina P, Ceballos D, Almela P, Navarro-Llavat M, Robles-Alonso V, Vega-Lopez AB, Moraleja I, Novella MT, Castano-Milla C, Sanchez-Torres A, Benitez JM, Rodriguez C, Castro L, Garrido E, Domenech E, Garcia-Planella E, Gisbert JP. Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study. Am J Gastroenterol. 2017 Jan;112(1):120-131. doi: 10.1038/ajg.2016.569. Epub 2016 Dec 13.
• Background Gisbert JP, Panes J. Loss of response and requirement of infliximab dose intensification in Crohn's disease: a review. Am J Gastroenterol. 2009 Mar;104(3):760-7. doi: 10.1038/ajg.2008.88. Epub 2009 Jan 27.
• Background Gisbert JP, Marin AC, Chaparro M. Systematic review: factors associated with relapse of inflammatory bowel disease after discontinuation of anti-TNF therapy. Aliment Pharmacol Ther. 2015 Aug;42(4):391-405. doi: 10.1111/apt.13276. Epub 2015 Jun 15.
• Background Felice C, Pugliese D, Guidi L, Marzo M, Andrisani G, Papa A, et al. Retreatment with infliximab in inflammatory bowel disease: tolerability and effectiveness of different re-induction regimens. J Crohns Colitis. 2014;8 (suppl.1):P363
• Background Cabriada JL, Vera I, Domenech E, Barreiro-de Acosta M, Esteve M, Gisbert JP, Panes J, Gomollon F; Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU). [Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis on the use of anti-tumor necrosis factor drugs in inflammatory bowel disease]. Gastroenterol Hepatol. 2013 Mar;36(3):127-46. doi: 10.1016/j.gastrohep.2013.01.002. Epub 2013 Feb 20. No abstract available. Spanish.
• Background D'Haens G, Feagan B, Colombel JF, Sandborn WJ, Reinisch W, Rutgeerts P, Carbonnel F, Mary JY, Danese S, Fedorak RN, Hanauer S, Lemann M; International Organization for Inflammatory Bowel Diseases (IOIBD) and the Clinical Trial Committee Clincom of the European Crohn's and Colitis Organisation (ECCO). Challenges to the design, execution, and analysis of randomized controlled trials for inflammatory bowel disease. Gastroenterology. 2012 Dec;143(6):1461-9. doi: 10.1053/j.gastro.2012.09.031. Epub 2012 Sep 20.
• Background Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P. Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 2004 Oct;60(4):505-12. doi: 10.1016/s0016-5107(04)01878-4.
• Background Kamm MA, Sandborn WJ, Gassull M, Schreiber S, Jackowski L, Butler T, Lyne A, Stephenson D, Palmen M, Joseph RE. Once-daily, high-concentration MMX mesalamine in active ulcerative colitis. Gastroenterology. 2007 Jan;132(1):66-75; quiz 432-3. doi: 10.1053/j.gastro.2006.10.011. Epub 2006 Oct 12.
• Background Alcala MJ, Casellas F, Fontanet G, Prieto L, Malagelada JR. Shortened questionnaire on quality of life for inflammatory bowel disease. Inflamm Bowel Dis. 2004 Jul;10(4):383-91. doi: 10.1097/00054725-200407000-00009.
• Background Vergara M, Montserrat A, Casellas F, Maudsley M, Gallardo O, Ricart E, Calvet X. Validation of the Spanish Work Productivity and Activity impairment questionnaire: Crohn's disease version. Eur J Gastroenterol Hepatol. 2009 Jul;21(7):809-15. doi: 10.1097/MEG.0b013e32830f4c9e.
• Background Chaparro M, Panes J, Garcia V, Manosa M, Esteve M, Merino O, Andreu M, Gutierrez A, Gomollon F, Cabriada JL, Montoro MA, Mendoza JL, Nos P, Gisbert JP. Long-term durability of infliximab treatment in Crohn's disease and efficacy of dose "escalation" in patients losing response. J Clin Gastroenterol. 2011 Feb;45(2):113-8. doi: 10.1097/MCG.0b013e3181ebaef9.
• Background Brooks AJ, Sebastian S, Cross SS, Robinson K, Warren L, Wright A, Marsh AM, Tsai H, Majeed F, McAlindon ME, Preston C, Hamlin PJ, Lobo AJ. Outcome of elective withdrawal of anti-tumour necrosis factor-alpha therapy in patients with Crohn's disease in established remission. J Crohns Colitis. 2017 Dec 4;11(12):1456-1462. doi: 10.1016/j.crohns.2014.09.007.
• Gisbert JP, Donday MG, Riestra S, Lucendo AJ, Benitez JM, Navarro-Llavat M, Barrio J, Morales-Alvarado VJ, Rivero M, Busquets D, Leo Carnerero E, Merino O, Nantes Castillejo O, Navarro P, Van Domselaar M, Gutierrez A, Alonso-Abreu I, Mejuto R, Fernandez-Salazar L, Iborra M, Martin-Arranz MD, Pineda JR, Sampedro MJ, Serra Nilsson K, Bouhmidi A, Batista L, Munoz Villafranca C, Rodriguez-Lago I, Ceballos D, Guerra I, Manosa M, Marin Jimenez I, Torrella E, Vera Mendoza M, Casanova MJ, de Francisco R, Arias-Gonzalez L, Marin Pedrosa S, Garcia-Bosch O, Garcia-Alonso FJ, Delgado-Guillena P, Garcia MJ, Torrealba L, Nunez-Ortiz A, Vicuna Arregui M, Bosca-Watts MM, Blazquez I, Acosta D, Garre A, Baldan M, Martinez C, Barreiro-de Acosta M, Domenech E, Esteve M, Garcia-Sanchez V, Nos P, Panes J, Chaparro M; EXIT Study group of GETECCU. Withdrawal of antitumour necrosis factor in inflammatory bowel disease patients in remission: a randomised placebo-controlled clinical trial of GETECCU. Gut. 2025 Feb 6;74(3):387-396. doi: 10.1136/gutjnl-2024-333385.

Drugs

Indications