Efficacy and Safety of Advanced Therapies for Moderately to Severely Active Ulcerative Colitis at Induction and Maintenance: An Indirect Treatment Comparison Using Bayesian Network Meta-analysis

Lay Summary Indirect evidence suggests upadacitinib may be more efficacious than other advanced therapies at achieving clinical response, clinical remission, and endoscopic response over 1 year for moderately to severely active ulcerative colitis patients, with similar safety assessments across advanced therapies. Background Given rapid innovation in advanced therapies for moderately to severely active ulcerative colitis (UC), we investigated their comparative efficacy and safety during induction and maintenance through network meta-analysis. Methods Using Bayesian methods, endpoints of clinical remission and clinical response per Full Mayo score, and endoscopic improvement were assessed in bio-naive and -exposed populations. Safety was assessed in overall populations by all adverse events (AEs), serious AEs, discontinuation due to AEs, and serious infections. Phase 3 randomized controlled trials were identified via systematic literature review, including the following advanced therapies: infliximab, adalimumab, vedolizumab, golimumab, tofacitinib, ustekinumab, filgotinib, ozanimod, and upadacitinib. Random effects models were used to address between-study heterogeneity. Intent-to-treat (ITT) efficacy rates were calculated by adjusting maintenance outcomes by likelihood of induction response. Results Out of 48 trials identified, 23 were included. Across all outcomes and regardless of prior biologic exposure, ITT efficacy rates were highest for upadacitinib, owing to its highest ranking for all efficacy outcomes in induction and for all but clinical remission during maintenance among bio-naive induction responders. For all advanced therapies versus placebo, there were no significant differences in serious AEs or serious infections across therapies. For all AEs, golimumab had higher odds versus placebo during maintenance; for discontinuation due to AEs, upadacitinib had lower odds versus placebo during induction, while ustekinumab and vedolizumab had lower odds versus placebo during maintenance. Conclusions Upadacitinib may be the most efficacious therapy for moderately to severely active UC based on ITT analyses, with similar safety across advanced therapies.