Relapse rates and predictors for relapse in a real-life cohort of IBD patients after discontinuation of anti-TNF therapy

Abstract

Objective: We investigated relapse rates after anti-tumor necrosis factor (anti-TNF) withdrawal in inflammatory bowel disease (IBD) patients, response to restart of anti-TNF treatment and predictors for relapse.

Methods: IBD patients in remission receiving infliximab or adalimumab treatment for ≥1 year who discontinued treatment were included. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results: In total, 101 patients were included (77 CD, 24 UC). A total of 56 patients (55%) experienced a relapse (CD 38, UC 18) with a median time to relapse of 32 and 18 months in CD and UC, respectively. Of patients that were retreated with the same anti-TNF agent, 84% responded. A trough serum concentration ≥2 µg/ml within 1 year prior to anti-TNF discontinuation was associated with a higher relapse rate in CD patients (HR 2.89; p = .018), which was more evident in patients requiring retreatment with biologicals, bowel-related surgery or experimental medication (HR: 4.18; p = .009). A young age (<17 years) at diagnosis was associated with a higher relapse rate (HR: 2.29; p = .040) and fecal calprotectin levels <25 µg/g with a lower relapse rate in CD patients (HR: 0.34; p = .041). Relapse rates, requiring treatment with biologicals or experimental medication, was lower in UC patients who continued immunosuppressive treatment (HR: 0.26; p = .042).

Conclusions: Approximately 55% of patients relapsed after anti-TNF withdrawal with a median time to relapse of 32 and 18 months in CD and UC, respectively. Retreatment with the same anti-TNF was successful in 84% of patients.

Keywords:

• Anti-TNF
• IBD
• Crohn’s disease
• ulcerative colitis
• discontinuation
• relapse

Disclosure statement

S. Bots has served as speaker for Abbvie, Merck, Sharp & Dome, Takeda, Jansen Cilag, Pfizer and Tillotts. S. Kuin has no potential conflicts of interest to declare. M. Löwenberg has served as speaker and/or principal investigator for: Abbvie, Celgene, Covidien, Dr. Falk, Ferring Pharmaceuticals, Gilead, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme, Pfizer, Protagonist therapeutics, Receptos, Takeda, Tillotts, Tramedico. He has received research grants from AbbVie, Merck Sharp & Dohme, Achmea healthcare and ZonMW. C. Ponsioen has served as advisor to Takeda and Pliant, has received speaker’s fees from Takeda, Tillotts, Abbvie, and received research grants form Takeda. M. Duijvestein has served as advisor for Echo pharma and Robarts Clinical Trials, reports nonfinancial support from Dr. Falk Pharma, and received speaker fees from Janssen, Merck & Co., Inc., Pfizer, Takeda and Tillotts Pharma. K. Gecse has served as speaker and/or advisor for Amgen, AbbVie, Biogen, Boehringer Ingelheim, Ferring, Hospira, Immunic AG, Janssen, MSD, Pfizer, Samsung Bioepis, Sandoz, Takeda, Tigenix and Tillotts. G. D’Haens has served as advisor for Abbvie, Ablynx, Allergan, Amakem, Amgen, AM Pharma, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, DrFALK Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Hospira/Pfizer, Immunic, Johnson and Johnson, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, Prometheus laboratories/Nestle, Progenity, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts and Vifor. No external funding was obtained for this study.