S1910 Biologics and Small Molecule Inhibitors for Mucosal Healing in Ulcerative Colitis: A Comparative Meta-Analysis of Endoscopic Outcomes

Introduction: Mucosal healing in ulcerative colitis (UC) is a validated therapeutic goal linked to sustained clinical remission and decreased colectomy rates. Both biologics and small molecule inhibitors (SMIs) are approved for moderate-to-severe UC; however, comparative data regarding their effectiveness in achieving endoscopic healing remain limited and fragmented. This study aimed to compare the mucosal healing efficacy of biologic therapies and SMIs in UC through a pooled analysis of randomized controlled trials (RCTs), with emphasis on endoscopic endpoints and safety profiles. Methods: A systematic review and meta-analysis was performed per PRISMA guidelines. Databases searched included PubMed (2020–2025), Cochrane Central (2010–2025), and Google Scholar (2015–2025). RCTs evaluating biologics (n = 4) or SMIs (n = 3) vs placebo or standard care in adult UC patients were included. The primary outcome was mucosal healing, defined as a Mayo endoscopic subscore ≤1. Secondary outcomes included treatment-related adverse events (AEs). Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using random-effects models. Statistical heterogeneity was assessed with the I² statistic. Results: Seven RCTs comprising 2,103 patients were included. Biologics significantly improved mucosal healing compared to control (RR: 1.68; 95% CI: 1.24–2.27; I² = 46%). SMIs also showed a significant effect (RR: 1.55; 95% CI: 1.19–2.03; I² = 35%). Indirect comparison between biologics and SMIs revealed no significant difference (RR: 1.08; 95% CI: 0.83–1.41). Adverse events were comparable between groups (pooled RR: 1.03; 95% CI: 0.89–1.19; I² = 21%). Subgroup analysis indicated a more rapid onset of response with SMIs, particularly tofacitinib. Conclusion: Biologics and SMIs both confer significant benefits in promoting mucosal healing in UC. No therapeutic class demonstrated clear superiority in efficacy or safety. Clinical decision-making should integrate patient-specific factors such as response kinetics, adverse event risk, and prior treatment exposure. These findings underscore the necessity for direct comparative trials to further refine treatment algorithms in ulcerative colitis.