S120 Mirikizumab Improves Patient Assessments of Disease Severity and Change in Disease Activity in Patients With Moderately-to-Severely Active Ulcerative Colitis

Abstract

Background: The Patient’s Global Rating of Severity (PGRS) Scale is a single item patient-reported questionnaire to assess disease symptom severity over the past 24 hours. The Patient’s Global Rating of Change (PGRC) is another single item patient-reported instrument to assess change in their symptom(s) since starting treatment. Mirikizumab, an anti-IL23p19 antibody, has demonstrated safety and efficacy versus placebo across clinical remission, symptomatic remission, endoscopic and histologic endpoints in patients with moderately-to-severely active ulcerative colitis (UC) in Phase 3, double-blind, 12-week induction study (LUCENT-1/NCT03518086) and 40-week maintenance study (LUCENT-2/NCT03524092). Here, we report the post-hoc analysis results of PGRS and PGRC scores from LUCENT-1 and LUCENT-2 trials. Methods: In LUCENT-1, 1,281 patients were randomly assigned 3:1 to receive mirikizumab 300 mg or placebo intravenously every 4 weeks (Q4W). Patients who achieved clinical response to mirikizumab by Week 12 of LUCENT-1 (N = 544) were re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo Q4W for 40 weeks in LUCENT-2. The primary outcome measure was the percentage of patients with clinical remission based on modified Mayo score at Week 12 in LUCENT-1 and Week 40 in LUCENT-2. The 6-point PGRS scale (1 = none to 6 = very severe) was recorded daily in an electronic diary, and the weekly average scores for PGRS were calculated. The 7-point PGRC scale (from 1 = very much better, 4 = no change, to 7 = very much worse) was recorded at Weeks 4, 8, 12 and 52. Change from baseline in PGRS and PGRC scores were analyzed using analysis of covariance models with modified baseline-observation-carried-forward method to handle missing data, adjusting for treatment, baseline value, and stratification factors. Results: In LUCENT-1, the PGRS (mean ± standard deviation) scores at baseline were 4.24 ± 0.82 in the mirikizumab 300 mg group and 4.28 ± 0.81 for placebo. The least-squares mean (LSM) change from baseline for PGRS was statistically greater in patients given mirikizumab 300 mg than placebo, starting at Week 2 (LSM [standard error] mirikizumab vs placebo: -0.39 [0.03] vs -0.28 [0.05], P = 0.03) and continued to increase at Week 12 (-1.16 [0.04] vs -0.69 [0.07], P < 0.001). At Week 40 in LUCENT-2 (52-week treatment), patients treated with mirikizumab 200 mg compared to placebo continued to report significant improvement in PGRS (mirikizumab vs placebo: -2.04 [0.07] vs -1.39 [0.103] P < 0.001). For PGRC, patients treated with mirikizumab had a significantly greater improvement, with lower mean scores compared to placebo at Week 4 (mirikizumab vs placebo: 2.8 [0.04] vs 3.2 [0.06], P < 0.001), Week 12 (2.3 [0.05] vs 3.0 [0.08], P < 0.001), and Week 52 (1.6 [0.06] vs 1.9 [0.10], P = 0.009). Conclusion(s): Mirikizumab treatment in patients with moderately-to-severely active UC significantly improved patient self-assessment of disease symptoms. Improvement was achieved as early as Week 2 for PGRS and Week 4 for PGRC and improvements were sustained through Week 52. These data support improvement in patients’ health status from a patient perspective.