Abstract Background Mirikizumab (miri) is a monoclonal antibody, selectively targeting the IL-23p19 subunit, modulating signaling pathways implicated in the pathogenesis of inflammatory bowel disease. We evaluated the induction efficacy and safety of miri in the LUCENT-1 (NCT03518086) East Asian (EA) subpopulation. Methods Total of 351 conventional-failed or biologic/tofacitinib (bio/tofa)-failed EA adult patients (China, Japan, and South Korea) with moderately to severely active ulcerative colitis (UC, Modified Mayo Score 4-9, endoscopic subscore ≥2) were randomized in the LUCENT-1 study (a Phase 3, multi-center, randomized, parallel-arm, double-blind, placebo-controlled trial). Patients were randomized in a 3:1 ratio to 300 mg miri (intravenous) or placebo every 4 weeks for 12 weeks. Randomization was stratified by bio/tofa failure status, baseline corticosteroid use, and baseline disease activity (Modified Mayo Score). The primary objective was to evaluate the superiority of miri over placebo in achieving clinical remission at Week 12 (W12). Key secondary endpoints included alternate clinical remission, clinical response, endoscopic remission, symptomatic remission, clinical response in biologic-failed patients, histologic-endoscopic mucosal improvement (HEMI), and bowel-movement urgency improvement. Analyses in the EA subpopulation were descriptive. For categorical endpoints, missing data was imputed as non-response. Bowel urgency change from baseline data was reported based on Mixed Model Repeated Measured analysis. Results Baseline characteristics were balanced between treatment groups. At W12, a greater proportion of miri-treated patients achieved clinical remission (23.5% vs. 6.0%; Δ = 16.9 95%CI: 9.7, 24.1) and alternate clinical remission (25.7% vs. 7.2%; Δ = 17.7 95%CI: 10.1, 25.3). Miri also improved key secondary endpoints at W12, including clinical response (60.4% vs. 26.5%; Δ = 32.7 95%CI: 21.5, 44.0), clinical response in biologic-failed patients (52.9% vs. 17.5%; Δ = 35.5 95%CI: 20.5, 50.5), symptomatic remission (42.9% vs. 15.7%; Δ = 26.3 95%CI: 16.3, 36.3), Endoscopic remission (34.0% vs. 10.8%; Δ = 21.9 95%CI: 13.1, 30.6), HEMI (23.1% vs. 6.0%; Δ = 16.8 95%CI: 9.5, 24.2), bowel-movement urgency improvement (-2.13 vs. -1.36; Δ = -0.77 95%CI: -1.36, -0.17). The frequencies of treatment-emergent adverse events (AE) were comparable between groups, with fewer serious AE and discontinuations due to AE in the miri group. Conclusion Efficacy and safety profiles of miri in the EA UC patients were consistent with LUCENT-1 overall population, supporting benefits of miri treatment in the EA UC population. Conflict of interest: Ran, Zhihua: No conflict of interest Shen, Jun: No conflict of interest Chen, Yan: No conflict of interest Fang, Hao: No conflict of interest Wang, Chengdang: No conflict of interest Zhang, Xiaolan: No conflict of interest Kobayashi, Taku: Grant: AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celtrion, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, Zeria Pharmaceutical Personal Fees: AbbVie, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical Tang, Dan: Employee and stockholder of Eli Lilly and Company Qian, Chenxi: Employee and stockholder of Eli Lilly and Company Yu, Jiao: Employee and stockholder of Eli Lilly and Company
Ran et al. (Thu,) studied this question.