S1508 Mirikizumab Improves Bowel Urgency and Correlates With Patient-Reported Outcomes in Moderately-to-Severely Active Ulcerative Colitis: LUCENT-URGE Trial

Introduction: Mirikizumab (miri) is an anti-IL-23p19 monoclonal antibody approved for the treatment of ulcerative colitis (UC) and Crohn’s disease. LUCENT-URGE (NCT05767021) is a multicenter, open-label, single-arm miri Phase 3b study in patients with moderately-to-severely active UC. LUCENT-URGE aimed to further explore the impact of miri on bowel urgency (BU). This analysis examined the relationship between the BU assessments and other symptoms associated with UC. Methods: Patients with UC and baseline BU (UNRS ≥3) were treated with intravenous miri 300 mg at week (W)0, W4, and W8, followed by subcutaneous miri 200 mg at W12, W16, W20, and W24. BU measures included the validated Urgency Numerical Rating Scale (UNRS) and the novel assessments of BU Frequency (BUF) and Shortest Weekly Stool Deferral Time (SDT). Additional patient-reported symptoms and tools used to collect patient-reported outcomes included Stool Frequency (SF), Rectal Bleeding (RB), Nocturnal Stool (NS), Abdominal Pain (AP) NRS, Fatigue NRS, Patient’s Global Rating of Severity (PGR-S), and Patient's Global Impression of Change (PGI-C). The Spearman correlation coefficient (95% confidence interval) was calculated to assess the correlation between continuous BU measures and UC symptoms measures at Baseline, W12, and W28. Results: BU and UC symptoms measures improved from Baseline to W12 and maintained improvements through W28. The UNRS, BUF, and SDT measures generally showed stronger correlations with other patient-reported measures at W12 and W28 compared to baseline. The strongest correlations were observed between the UNRS and BUF measures and SF, AP NRS, and Fatigue NRS. The BU measures were less associated with RB alone. SF measures demonstrated moderate correlations with UNRS and BUF. Fatigue NRS had a moderate correlation with UNRS throughout. PGR-S had moderate correlations with UNRS and weak correlations with BUF and SDT at Baseline, which increased to moderate by W28. All 3 BU measures showed moderate correlation with the PGR-S by W28. Conclusion: In patients with moderately to severely active UC treated with miri, improvements in all BU measures at W12 were sustained and improved through Week 28. Most correlation levels between BU measures and other symptoms were similar or increased during the study. Moderate correlations between all 3 BU measures and PGRS support that BU is an important component of patients’ overall symptom burden.