Withdrawal of TNF Antagonists in Patients with Inflammatory Bowel Disease in Remission: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background Tumor necrosis factor (TNF) antagonists are central to the management of inflammatory bowel disease (IBD), but concerns regarding long-term safety, infection risk, and costs have prompted interest in treatment de-escalation. Whether discontinuing TNF therapy in patients with sustained remission is safe remains uncertain. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TNF antagonist withdrawal with continuation in IBD patients in sustained remission. Databases including MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov were searched through July 2025. Eligible trials enrolled adults with Crohn’s disease or ulcerative colitis in clinical remission. Primary outcomes were relapse risk and sustained remission. Data were pooled using a random-effects model. Results Four RCTs comprising 485 patients were included. TNF antagonist withdrawal was associated with a significantly higher risk of relapse compared with continuation (RR: 3.00, 95% CI: 1.47–6.11). Time to relapse was also shorter in the withdrawal group (HR: 5.34, 95% CI: 2.05–13.92). Sustained clinical remission did not differ significantly between groups (RR: 0.83, 95% CI: 0.55–1.27). Withdrawal reduced infection risk (RR: 0.47, 95% CI: 0.25–0.90), while rates of gastrointestinal and serious adverse events were comparable. Conclusions Discontinuation of TNF antagonists in IBD patients in remission substantially increases the risk and accelerates the timing of relapse, though it lowers infection risk. Careful patient selection and close monitoring are essential if withdrawal is considered.