S1811 Mirikizumab Provides Sustained Long-Term Efficacy Up to 4 Years of Treatment for Ulcerative Colitis: Final Results From the LUCENT-3 Open-Label Extension Study

Introduction: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at Week (W) 12 and maintaining clinical remission through W152 in moderately-to-severely active ulcerative colitis. Here, we present efficacy and safety results through W212 of mirikizumab treatment from the open-label extension 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 induction responders, including patients with biologic failure, who entered LUCENT-3, with data shown for 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 bias of NRI and OC. Safety population N = 339. Results: Using mNRI (N = 179), among W52 mirikizumab maintenance remitters demonstrated clinical response in 79% at W212. W212 remission rates among W52 clinical remitters were 77% for symptomatic, 62% for clinical, 66% for endoscopic, 53% for histologic-endoscopic mucosal, 62% for CSF, and 60% for bowel urgency; 78% for Inflammatory Bowel Disease Questionnaire (IBDQ) response, and 73% IBDQ remission. Histologic-endoscopic mucosal improvement and bowel urgency clinically meaningful improvement at W212 were achieved in 54% and 75% of patients, respectively. Biologic Failed/Not Biologic Failed subgroup data demonstrated maintenance of efficacy. Stool frequency, rectal bleeding, bowel urgency, and abdominal pain symptom score reductions from induction baseline at W52 were sustained through W212. For W0-160 of LUCENT-3, serious AEs were reported in 12% patients, while 7% discontinued treatment due to an AE. AEs of special interest: opportunistic infection (4.4%), cerebrocardiovascular events (1.5%), and malignancy (1.5%). Liver enzymes ≥3 upper limit of normal (ULN) included alanine aminotransferase (2%) and aspartate aminotransferase (1%); total bilirubin level was ≥2 ULN (2%). Conclusion: Mirikizumab provides long-term symptomatic, clinical, endoscopic, histologic, corticosteroid-free, and quality-of-life sustained and durable maintenance of benefits up to 4 years in patients with UC, including for biologic failed patients, with no new safety concerns.