OP26 Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study

Abstract

Background Anti-IL23p19 inhibitors are emerging as promising treatment options for ulcerative colitis (UC). Mirikizumab (miri) is a humanized, IgG4 monoclonal antibody directed against the p19 subunit of IL-23, a key mediator in the pathogenesis of inflammatory bowel diseases. We assessed the induction efficacy and safety of miri with a Phase 3, multi-center, randomized, parallel-arm, double-blind, placebo (PBO)-controlled trial (LUCENT 1; NCT03518086) in patients with moderately to severely active UC (Modified Mayo Score 4–9 points and centrally read Mayo endoscopic subscore ≥2) who had inadequate response, loss of response, or intolerance to corticosteroids, immunosuppressants, biologic therapies, or tofacitinib. Methods Adult patients (N=1281) were randomized in a 3:1 ratio to receive blinded intravenous administration of 300 mg miri or PBO every 4 weeks for 12 weeks. Randomization was stratified by biologic failure status, baseline (BL) corticosteroid use, BL disease activity as measured by modified Mayo score, and world region. The primary objective was to test the hypothesis that miri was superior to PBO in inducing clinical remission at Week 12. Key secondary objectives were clinical response, endoscopic remission, symptomatic remission, clinical response in biologic-failed patients, histologic-endoscopic mucosal improvement, and improvement in bowel urgency at Week 12 (see Figure for endpoint definitions). Mixed Model for Repeated Measures was used to assess urgency; the Cochran-Mantel-Haenszel test, with missing data imputed as nonresponse, was used to assess all other outcomes. Results BL characteristics were balanced across the two treatment groups. A significantly greater proportion of patients treated with miri achieved clinical remission at Week 12 (Miri: 24.2%; PBO: 13.3%; Δ=11.1 [99.875%CI: 3.2, 19.1]; p=0.00006). Miri-treated patients achieved all key secondary endpoints, including a significantly greater average reduction in bowel urgency severity compared to PBO (p<0.00001). The frequencies of treatment-emergent adverse events in miri-treated patients were similar to PBO. There were numerically fewer serious adverse events (Miri: 27 [2.8%], PBO: 17 [5.3%]) and discontinuations due to adverse events (Miri: 15 [1.6%], PBO: 23 [7.2%]) in miri-treated patients compared to PBO. There were 2 colon malignancies in the miri arm (0.2%) and no deaths during the treatment period. Conclusion In this phase 3 UC study, 300mg miri IV demonstrated statistically significant and clinically meaningful improvements vs PBO in all primary and key secondary endpoints across clinical, endoscopic, histologic, and symptomatic measures, with an acceptable safety profile.

Improving IBD outcomes in the era of many treatment options

“…Similarly, the efficacy of another IL-23p19 antibody, guselkumab, was demonstrated in Crohn’s disease in the phase II GALAXI-1 trial 3 . IL-23p19 has also been successfully targeted in moderately to severely active ulcerative colitis with the monoclonal antibody mirikizumab 4 — the phase III trial has been completed and regulatory authorities are considering mirikizumab for clinical approval.…”

Questions to consider when caring for patients with ulcerative colitis

“…Mirikizumab has demonstrated efficacy in a phase 2 trial [62]. Preliminary data from a phase 3 trial confirm its efficacy to induce clinical response and remission as well as endoscopic remission in UC [63].…”

Psychometric evaluation of the Urgency NRS as a new patient-reported outcome measure for patients with ulcerative colitis

“…The data used in this study were from LUCENT-1, a phase 3 randomized, double-blind, parallel-arm trial of the safety and efficacy of mirikizumab for UC induction treatment in adults with moderately to severely active UC (NCT03518086) [ 6 ]. Participants were randomly assigned 3:1 to receive an intravenous infusion of mirikizumab 300 mg or placebo at weeks 0, 4, and 8 during a 12-week treatment period.…”