Systematic review with meta‐analysis: the effects of immunomodulator or biological withdrawal from mono‐ or combination therapy in inflammatory bowel disease

BACKGROUND: Withdrawal of treatment is a common therapeutic problem in patients with long‐standing remission of inflammatory bowel disease. AIMS: To evaluate the relapse rate in patients with quiescent inflammatory bowel disease after cessation of biologic or immunomodulator therapy. METHODS: We searched five databases for studies evaluating disease relapse after withdrawal of monotherapy or a drug from combination therapy in Crohn's disease or ulcerative colitis. In meta‐analysis, risk ratios (RR) were calculated with 95% confidence intervals (CI). RESULTS: Ten randomised controlled trials (587 patients) were included in the meta‐analysis, and another nine studies in systematic review. Withdrawal of immunomodulator monotherapy resulted in a significantly higher risk of relapse within 24 months of follow‐up compared to ongoing therapy in Crohn's disease, but not in ulcerative colitis (RR = 2.06, CI: 1.53‐2.77 and RR = 1.39, CI: 0.85‐2.26, respectively). Trial sequential analysis indicated that further studies with similar design are unlikely to change the significant association on relapse rates after withdrawing immunomodulator monotherapy in patients with Crohn's disease. Discontinuation of an immunomodulator from combination with biologics did not show a higher risk of relapse than continuation of both drugs (RR = 1.30, CI: 0.81‐2.08). The relapse rate increased after withdrawal of biologic monotherapy, whereas contradictory results were observed after biologic withdrawal from combination regimens. CONCLUSION: Continuing immunomodulator monotherapy should remain the preferred approach among patients with Crohn's disease, although long‐term toxicity is a concern. Further randomised controlled trials are warranted in ulcerative colitis and on combination regimens including biologics.