Efficacy of Advanced Medical Therapies in Patients With Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta‐Analysis
Abstract
To evaluate the absolute efficacy of approved advanced medical therapies (biologicals or small molecules) in adults with moderately to severely active ulcerative colitis (UC), compared with placebo or active comparators. We included Phase 3 and 4 randomised controlled trials (RCTs) evaluating FDA‐ or EMA‐approved advanced therapies in adults with moderately to severely active UC. PubMed, EMBASE, Cochrane, and major congress abstracts were searched through October 2024. Eligible RCTs compared these therapies to placebo or an active comparator and reported clinical remission, clinical response, endoscopic remission, and/or histological remission. Our primary outcome was clinical remission after induction (defined as a Mayo score ≤ 2 with no individual subscore > 1, including the endoscopic subscore). Random‐effects models estimated pooled absolute differences in outcome rates (risk differences; RDs) for induction and maintenance. Certainty of evidence was assessed using GRADE. The search yielded 7712 records, of which 25 RCTs (38 cohorts; 15,460 patients) met inclusion criteria. Of these, 20 RCTs (25 cohorts; 11,476 patients) reported induction outcomes, and 18 RCTs (19 cohorts; 6692 patients) reported maintenance outcomes. The pooled absolute difference (RD) for clinical remission after induction was +13.1% (95% CI: 10.3–16.0), increasing to +21.1% (95% CI: 16.4–25.7) for maintenance. Clinical response also favoured intervention, with RDs of +24.2% (95% CI: 19.7–28.6) for induction and +26.6% (95% CI: 20.3–33.0) for maintenance. Endoscopic remission was less frequently reported, and showed smaller but significant effects (induction RD +8.2%, 95% CI: 4.7–11.8; maintenance +13.6%, 95% CI: 8.5–18.7). Histological remission RDs were +12.5% (95% CI: 6.6–18.4) and +15.5% (95% CI: 9.0–22.0), respectively. Certainty of evidence was high for clinical remission and moderate‐to‐low for other outcomes due to limited reporting and heterogeneity. Advanced therapies favoured significant absolute benefits in inducing and maintaining remission in moderate‐to‐severe UC. These results provide a benchmark for future trials and non‐pharmacological interventions. This study was registered in PROSPERO (CRD42024599272)