S1686 Mirikizumab Provides Sustained Long-Term Efficacy Up to 4 Years of Treatment for Ulcerative Colitis: Extended Induction Results From the LUCENT-3 Open-Label Study

Introduction: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious inducing clinical remission at Week(W) 12 and maintaining clinical remission through W212 in patients with moderately-to-severely active ulcerative colitis (LUCENT-1: W0-W12, NCT03518086; LUCENT-2: W12-W52, NCT03524092; LUCENT-3: W52-W212, NCT03519945). Here we present efficacy and safety through W212 of mirikizumab extended induction from the open-label LUCENT-3 study. Methods: Symptomatic, clinical, endoscopic, histologic, corticosteroid-free (CSF), bowel urgency, quality-of-life, and adverse event (AE) outcomes are reported for mirikizumab extended induction (intravenous every 4W for 24W) responders, including patients with biologic failure, who entered LUCENT-3, with data from W52 maintenance remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC). mNRI uses multiple imputation for missing data and balances biases of NRI and OC. Efficacy population N = 52. Safety population N = 150. Results: Using mNRI, mirikizumab extended induction W52 clinical remitters demonstrated 74% clinical response at W212. Remission rates at W212 among W52 clinical remitters were: symptomatic remission, 71%; clinical remission, 54%; endoscopic remission, 60%; histologic-endoscopic mucosal remission, 43%; CSF remission, 49%; bowel urgency remission, 62%; and Inflammatory Bowel Disease Questionnaire remission, 76%. Bowel urgency clinically meaningful improvement at W212 was achieved in 70% of patients. Biologic Failed/Not Biologic Failed subgroup data also demonstrated maintenance of efficacy. Stool frequency, rectal bleeding, and bowel urgency score reductions from induction baseline at W52 for maintenance completers with mixed model repeated measures were sustained through W212. For W0-W160 of LUCENT-3, serious AEs were reported in 14% of patients, while 9% discontinued treatment due to an AE. Conclusion: For UC patients refractory to initial induction treatment, mirikizumab extended induction provides sustained long-term symptomatic, clinical, endoscopic, histologic, corticosteroid-free, and quality-of-life remission up to 4 years in patients with UC, including for biologic failed patients, with no new safety concerns.