Clinical Effect of Mirikizumab Treatment on Bowel Urgency in Patients with Moderately to Severely Active Ulcerative Colitis and the Clinical Relevance of Bowel Urgency Improvement for Disease Remission.
Dubinsky MC., Clemow DB., Hunter Gibble T., Li X., Vermeire S., Hisamatsu T., Travis SPL.
BackgroundBowel urgency reduces ulcerative colitis patients' quality of life. Mirikizumab, a p19-directed anti-IL-23 antibody, demonstrates ulcerative colitis efficacy. Mirikizumab efficacy to reduce bowel urgency and bowel urgency association with other endpoints were analyzed in 2 Phase 3 trials.MethodsLUCENT-1 (Induction): 1162 patients randomized 3:1 to intravenous 300 mg mirikizumab or placebo every 4 weeks for 12 weeks. LUCENT-2 (Maintenance): 544 mirikizumab responders during induction were re-randomized 2:1 to subcutaneous mirikizumab 200 mg or placebo every 4 weeks for 40 weeks (52 weeks of continuous treatment). Bowel urgency was measured using the Urgency Numeric Rating Scale (0-10); for patients with LUCENT-1 baseline score ≥3, bowel urgency clinically meaningful improvement (≥3-point decrease) and remission (score ≤1) rates in mirikizumab versus placebo groups were compared at Weeks 12 and 52. Associations between bowel urgency and other efficacy endpoints were assessed at Weeks 12 and 52.ResultsA significantly higher proportion of mirikizumab patients versus placebo achieved clinically meaningful improvement in bowel urgency and remission at Weeks 12 and 52. Significantly higher percentages of patients achieving bowel urgency clinically meaningful improvement or remission, compared with those who did not, also achieved endpoints for clinical, corticosteroid-free, endoscopic, and symptomatic remission; clinical response; normalized fecal calprotectin and C-reactive protein; and improved quality of life.ConclusionsIn patients with ulcerative colitis, bowel urgency improvement was associated with better clinical outcomes than in patients without improvement during induction and maintenance. A greater proportion of mirikizumab patients achieved sustainable bowel urgency improvement and remission compared to placebo patients.