(P032) MATCHING-ADJUSTED INDIRECT COMPARISON ON CLINICAL REMISSION FOR MIRIKIZUMAB AND RISANKIZUMAB MAINTENANCE IN THE TREATMENT OF ADULTS WITH MODERATELY-TO-SEVERELY ACTIVE ULCERATIVE COLITIS

Purpose: We indirectly compared efficacy of mirikizumab (MIR) and risankizumab (RIS) in patients with moderately-to-severely active ulcerative colitis (UC) using 1-year maintenance data from Phase 3 trials (MIR: NCT03524092; RIS: NCT03398135).^1,2

Methods: Both COMMAND study¹ for RIS and LUCENT-2 study² for MIR re-randomized clinical responders from induction to either the placebo-withdrawal or the active arms (RIS 180mg and 360mg subcutaneous [SC] in COMMAND, MIR 200mg SC in LUCENT-2) for another 40 weeks (W). Indirect comparison between RIS and MIR could have challenges due to the re-randomized withdrawal study design and potentially differential “carry-over" effects of previous treatment to the placebo-withdrawal arm. RIS and MIR have similar mechanisms of action and placebo clinical response rate. We indirectly compared MIR 200mg and RIS 180mg and 360mg on clinical remission rates at W40 of maintenance. Bucher’s method without baseline adjustments and anchored matching-adjusted indirect comparisons (MAIC) per study level and per individual arm matching that matched patient-level baseline variables from LUCENT-2 with baseline variables from COMMAND were conducted. The placebo arm from re-randomization withdrawal in both studies was used as the anchor. Missing outcome data were imputed as non-response.

Results: In the re-randomized withdrawal studies, significantly greater clinical remission rates compared to placebo were reported for RIS (40.2% for 180mg, 37.6% for 360mg) vs. placebo (25.1%) and MIR (50.7%) vs. placebo (26.6%) for the modified Mayo Score (mMS) 5-9 population. Baseline characteristics of aggregate LUCENT-2 population were well-matched to those from aggregate COMMAND population using per study level matching (Table). MIR showed consistently numerically higher clinical remission rate than RIS during maintenance in both mMS4-9 and mMS5-9 patient populations with or without matching of baseline characteristics. From MAIC analysis, consistently higher proportions of patients achieved clinical remission with MIR maintenance treatment (Table). Results from per individual arm matching confirmed the findings.

Conclusion: MAIC results further support the high efficacy profile of MIR for maintaining clinical remission, providing additional information for treatment decisions for UC within the interleukin-23p19 class.

1.Louis E, et al. JAMA 2024;e2412414

2.D'Haens G, et al. N Engl J Med 2023;388:2444-2455