S2043 Efficacy of Advanced Therapies for Naïve and Experienced Patients for Moderately-to-Severely Active Ulcerative Colitis: A Bayesian Network Meta-Analysis

Introduction: The evolving advanced treatment landscape for moderately-to-severely active ulcerative colitis (UC) warrants an updated efficacy assessment of a 2022 network meta-analysis (NMA) that included etrasimod as the newest approved agent. Since then, additional therapies including mirikizumab (MIR), risankizumab (RZB), and guselkumab (GUS) have been approved. Methods: A systematic literature review up to 10/22/2024 was performed. A Bayesian, multinomial, fixed-effect model was used to model clinical remission and response at the end of induction and among induction phase responders at the end of maintenance, stratified by prior exposure to advanced therapies (AT-naïve [AT-N] vs AT-experienced [AT-E]). Results are reported as median relative risk (RR) with 95% credible intervals (CrI) of treatment vs comparator. Results: Four additional studies each for induction and maintenance were included. Results of pairwise comparisons across agents from the 2022 NMA were consistent. For additional agents, most pairwise comparisons had no significant difference at the end of induction and maintenance. For AT-N induction clinical remission, MIR 300 mg was significantly less effective vs RZB 1200 mg (RR, 0.7; 95% CrI, 0.5-1.0) and GUS 200 mg was favored vs MIR 300 mg (1.6, 1.1-1.2). Adalimumab (ADA) and filgotinib had significantly lower likelihoods of remission vs RZB and GUS. For AT-E induction, ADA 160/80 mg (0.3, 0.2-0.7) and ozanimod 1 mg (0.5, 0.2-1.0) were less favorable vs GUS. For AT-N maintenance clinical remission, tofacitinib (TOF) 10 mg and upadacitinib (UPA) 30 mg were significantly more effective vs infliximab 120 mg SC (TOF: 1.3, 1.0-1.9; UPA: 1.3, 1.0-2.0), MIR 200 mg (TOF: 1.3, 1.0-1.9; UPA: 1.3, 1.0-2.0), and RZB 180 mg (TOF: 1.7, 1.1-3.3; UPA: 1.7, 1.1-3.5) and RZB 360 mg (TOF: 1.5, 1.0-2.7; UPA: 1.5, 1.0-2.9). For AT-E patients, most treatments were more effective vs RZB; RZB 360 mg was not significant vs PBO (0.8, 0.6-1.0). Clinical response findings were similar for induction and maintenance. Conclusion: Pairwise comparisons of the updated NMA were consistent with the 2022 NMA and most new comparisons demonstrated similar efficacy. Differences for new agents included that RZB and GUS were favorable over MIR, ADA and FIL for AT-N induction, and RZB was less favorable vs most agents for AT-E maintenance. Future head-to-head and real-world studies should be assessed to clarify these findings.