S1736 Mirikizumab Demonstrates Durable and Sustained Maintenance of Endoscopic and Histologic Outcomes at 4 Years in Patients With Moderately-to-Severely Active Ulcerative Colitis: LUCENT-3 Open-Label Extension Study

Introduction: Mirikizumab (MIRI), an anti-interleukin (IL)-23p19 monoclonal antibody, has previously shown maintained endoscopic and histologic remission with continuous treatment in patients with moderately-to-severely active ulcerative colitis (UC). We evaluated endoscopic and histologic outcomes after 4 years of continuous MIRI treatment. Methods: The study designs for the continuous phase 3 LUCENT-1 (NCT03518086) 12-week induction, LUCENT-2 (NCT03524092) 40-week maintenance, and LUCENT-3 (NCT03519945) open-label long-term extension studies have been described. This analysis focused on patients who were Week (W)52 MIRI maintenance clinical remitters. Durable maintenance of outcomes included endoscopic remission (ER), endoscopic normalization (EN), histologic improvement (HI), histologic remission (HR), histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR), and alternate HEMR at 4 years. Sustained maintenance of ER, HI, HR, HEMI, and HEMR across 2, 3, and 4 years among the patients who achieved the respective endpoint at 1 year was also assessed. Discontinuations or missing data were handled by modified non-responder imputation (mNRI) and observed case (OC). Results: The pre-treatment baseline characteristics for W52 clinical remitters (N = 179): 59.2% were men, the mean (standard deviation (SD)) age was 43.8 (14.3) years. Mean (SD) of baseline modified Mayo Score was 6.6 (1.3) and 33.0% had prior biologic or tofacitinib failure. After 4 years of continuous MIRI treatment, 81.3% of patients achieved ER, 67.9% achieved HR, 67.9% achieved HEMI, and 66.0% achieved HEMR (OC data). The percentages of patients who maintained outcomes at 2, 3, and 4 years among the patients who achieved the respective endpoint at 1 year were 70.0%, 57.7%, 50.0%, 53.8%, and 47.1% for ER, HI, HR, HEMI, and HEMR, respectively (OC data). Conclusion: In LUCENT-3, endoscopic and histologic outcomes, key components of comprehensive disease control, showed durable maintenance at 4 years of continuous mirikizumab treatment. These outcomes also showed sustained maintenance from 1 year across 2, 3, and 4 years. This is the only p19-targeted IL-23 antibody in UC showing endoscopic and histologic outcomes at 4 years.