Abstract

Abstract Background The modified Mayo score (mMS) is a measure for ulcerative colitis (UC) disease activity. Recent US Food and Drug Administration guidance for moderately to severely active UC trials suggests that patients should have baseline mMS of 5–9 including an endoscopy score of at least 2, opposed to the previous range of 4–9. This disclosure reports results from patients with UC with baseline mMS of 5–9 who received mirikizumab, a monoclonal antibody directed against the interleukin-23 p19 subunit, or placebo in the phase 3 LUCENT trials. Methods Mirikizumab was evaluated in the randomized, double-blind, placebo-controlled LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) trials, and the ongoing long-term LUCENT-3 (NCT03519945) trial, which use mMS 4-9. Analyses for patients with baseline mMS of 5-9 (excluding patients with mMS of 4) were conducted according to LUCENT trial statistical analysis plans. Categorical efficacy endpoints were summarized using proportions and confidence intervals. Continuous efficacy endpoints are presented as least-squares mean (standard error) changes from baseline. Results Mirikizumab demonstrated efficacy for the primary endpoint of clinical remission and major secondary endpoints including clinical response, endoscopic improvement, histologic–endoscopic mucosal improvement/remission, bowel urgency remission, and corticosteroid-free remission. Importantly, mirikizumab exhibited greater improvements versus placebo in the Inflammatory Bowel Disease Questionnaire, fatigue, symptomatic remission, and work productivity. Finally, mirikizumab demonstrated long-term (104-week) sustained, durable efficacy across all studied endpoints. No new safety signals were identified during 2-year follow-up. Conclusions Mirikizumab delivered significant clinical benefit for patients with baseline mMS of 5-9 and demonstrated a favorable safety profile.