Mirikizumab impact on disease clearance in patients with moderately to severely active ulcerative colitis: analysis of a pre-specified LUCENT trial endpoint.

Abstract

Background and aims: Concurrent achievement of symptomatic, endoscopic, and histologic remission, known as disease clearance, has been proposed as a treatment target in ulcerative colitis. Mirikizumab, an anti-interleukin-23 p19 antibody, has demonstrated long-term efficacy and safety, as reported in the LUCENT Phase 3 trials (NCT03518086, NCT03524092, and NCT03519945). The current analysis evaluates the impact of mirikizumab on disease clearance and the association with other clinical and patient-reported outcomes (PROs).

Methods: LUCENT methods have previously been reported. The proportion of patients achieving disease clearance was determined through week (W)104. Association analyses were assessed between disease clearance and PROs (IBDQ, SF-36, WPAI:UC, PGRS, and PGRC), and early disease clearance and subsequent clinical outcomes (clinical, corticosteroid-free, endoscopic, histological, histologic-endoscopic, bowel urgency, stool frequency, and rectal bleeding).

Results: The proportions of patients achieving disease clearance with mirikizumab at W12, W52, and W104 were 16.0%, 36.4%, and 51.3%, respectively. Mirikizumab-treated patients with disease clearance showed greater PRO improvements through W52 than those without. Early clearance at W12 was associated with significantly better clinical outcomes at later time points, except for bowel urgency remission at W52. This trend was repeated for clinical outcomes at W104 in patients who achieved disease clearance at W52.

Conclusions: Mirikizumab consistently demonstrated disease clearance across induction, maintenance, and long-term studies. The attainment of disease clearance was associated with greater improvement in PROs, and early achievement of disease clearance was associated with better long-term outcomes, including clinical remission, corticosteroid-free remission, endoscopic and histological outcomes, reduced stool frequency, and rectal bleeding.