Maintenance of Remission Among Patients With Crohn's Disease on Antimetabolite Therapy After Infliximab Therapy Is Stopped
Background & Aims
It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse.
Methods
We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model.
Results
After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% ± 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 × 109/L, and levels of hemoglobin ≤145 g/L, C-reactive protein ≥5.0 mg/L, and fecal calprotectin ≥300 μg/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse.
Conclusions
Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers.
Keywords: Inflammatory Bowel Disease , IBD , Clinical Trial , Stopping Therapy , Factors That Contribute to Relapse
Abbreviations used in this paper: CDEIS, Crohn's Disease Endoscopic Index of Severity, GETAID, Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives, hsCRP, high-sensitivity C-reactive protein, TNF, tumor necrosis factor
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This article has an accompanying continuing medical education activity on page e31. Learning Objective: Upon completion of this exercise, successful learners will be able to assess the risk of relapse and the response to potential re-treatment in Crohn's disease patients in whom infliximab treatment would be stopped after prolonged stable remission under combined therapy with antimetabolite and infliximab.
Conflicts of interest The authors disclose the following: E.L. has received consultancy fees from Schering-Plough, Abbott Laboratories, MSD, Ferring Pharmaceuticals, Shire, Millennium Pharmaceuticals, and UCB; research or educational grants from MSD, Schering-Plough, AstraZeneca, and Abbott Laboratories; and lecture fees from Abbott Laboratories, AstraZeneca, Ferring Pharmaceuticals, MSD, Schering-Plough, Falk, Menarini, Chiesi, and Nycomed. Y.B. has received consultancy fees and lecture fees from Norgine, Abbott Laboratories, Schering-Plough, and Ferring Pharmaceuticals. D.L. has received consultancy fees from Norgine and Ferring Pharmaceuticals and has received lecture fees from Norgine, Ferring Pharmaceuticals, Abbott Laboratories, and Schering-Plough. G.S. has received lecture fees from Abbott Laboratories and Schering-Plough. M.D. has received an educational grant from Schering-Plough. G.P. has received consultancy fees from Roche and LFB and has received lecture fees from Janssen-Cilag. J.-F.C. has received consulting fees from Abbott Laboratories, ActogeniX, Albireo Pharma, Amgen, AstraZeneca, Bayer AG, Biogen Idec, Boehringer Ingelheim GmbH, Bristol-Myers Squibb, Cellerix, Centocor, ChemoCentryx, Cosmo Technologies, Danone Research, Elan Pharmaceuticals, Genentech, Giuliani SpA, Given Imaging, GlaxoSmithKline, Hutchison MediPharma, Merck Sharp & Dohme Corp, Millennium Pharmaceuticals (now Takeda), Neovacs, Ocera Therapeutics, Pfizer, Shire Pharmaceuticals, Prometheus Laboratories, Sanofi-Aventis, Schering-Plough, Synta Pharmaceuticals Corp, Teva, Therakos, UCB Pharma, and Wyeth; has served on advisory committees for Abbott Laboratories, Centocor, Danone Research, Elan Pharmaceuticals, Merck Sharp & Dohme, Millennium Pharmaceuticals (now Takeda), Schering-Plough, and UCB Pharma; has received speaking fees from Abbott Laboratories, Centocor, Elan Pharmaceuticals, Given Imaging, Merck Sharp & Dohme Corp, Otsuka America Pharmaceutical, Schering-Plough, Shire Pharmaceuticals, Tillotts Pharma, and UCB Pharma; and has received grant support from Abbott Laboratories, AstraZeneca, Ferring Pharmaceuticals, Merck Sharp & Dohme Corp, Schering-Plough, and UCB Pharma. The remaining authors disclose no conflicts.
Funding The GETAID received unrestricted study grants from the Association François Aupetit and the Société Nationale Française de Gastroentérologie.
PII: S0016-5085(11)01293-5
doi:10.1053/j.gastro.2011.09.034
© 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
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