OP34 Mirikizumab Demonstrates Rapid Improvements in Bowel Urgency Severity, Bowel Urgency Frequency, and Stool Deferral Time in Patients with Moderately-to-severely Active Ulcerative Colitis: 12-Week Interim Results from the Phase 3b LUCENT-URGE Trial

Abstract Background Bowel urgency (BU) is a common, under-recognized and debilitating symptom among patients with ulcerative colitis (UC). LUCENT-URGE is a Phase 3b, open-label, single-arm 28-week (W) study in adults with moderately-to-severely active UC and BU (Urgency Numeric Rating Scale [UNRS] ≥3) at baseline treated with mirikizumab (MIRI) (NCT05767021). BU was assessed using the validated UNRS1 and 2 new BU assessments: BU Frequency (BUF) and Stool Deferral Time (SDT). These 3 BU measures (UNRS, BUF, SDT) and clinical endpoints provide a more comprehensive understanding of BU and the impact of MIRI treatment. Here, we report W12 interim analysis results. Methods Patients were treated with intravenous (IV) MIRI 300 mg at W 0, 4 and 8, followed by 200 mg subcutaneous at W12 and every 4 weeks up to W28. The primary endpoint, BU severity (UNRS) at W12, was assessed by change from baseline. BUF improvement was assessed by change from baseline at W12. SDT was reported in minutes and categorized as (4) Severe: <1 min; (3) Moderate-Severe: 1-2 min: (2) Moderate: 2-5 min; (1) Mild: 5-15 min; (0) None: ≥15 minutes. Results 172 patients were enrolled from 8 countries. At baseline, mean (± standard deviation [SD]) modified Mayo score [MMS]) was 6.8±1.3; 64% of patients had severe disease activity (MMS 7-9), mean duration of UC was 8.0±8.2 years, mean UNRS score was 6.9 ±1.6, mean BUF was 6.9±3.7. UNRS, BUF, and SDT improved from baseline to W12 (Figure 1). At W12, 63% patients achieved clinical response and 44% achieved both clinical response and UNRS clinically meaningful improvement (≥3 point decrease). Correlations between UNRS and BUF, and between UNRS and SDT at baseline, W12, and W12 change from baseline were of similar magnitude (Spearman correlation coefficient range: 0.43-0.68). The safety profile of MIRI observed in LUCENT-URGE was consistent with the profile previously reported. Conclusion In patients with moderately-to severely active UC and BU, MIRI demonstrated improvement in BU measures with a decrease by more than 50% in BUF after 12W of treatment. Selecting patients with urgency and targeting BU improvement is a novel strategy to assess response to therapy for UC. Broader associations between BU and quality of life, UC symptoms, histopathologic findings, and gene expression data will be explored upon completion of the W28 LUCENT-URGE study. References 1.Dubinsky MC, Shan M, Delbecque L, et al. Psychometric evaluation of the Urgency NRS as a new patient-reported outcome measure for patients with ulcerative colitis. J Patient Rep Outcomes 2022; 6(1): 114.