P0894 Impact of Mirikizumab on Extraintestinal Manifestations of Crohn’s Disease in the VIVID-1 Study
Authors: Vavricka S R , Ananthakrishnan A , Long M , Melmed G , Narula N , Rubin D , Hon E , Carlier H , Moses R , Yu G , Zang H , Kucharzik T 
Published: January 2025

Abstract

Background
Mirikizumab, an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile for the treatment of moderately-to severely- active Crohn’s disease (CD) in the phase 3 VIVID-1 study1, a double-blind, placebo-controlled, active comparator study, which has been reported previously. Here we assess the impact of mirikizumab on extra-intestinal manifestations (EIMs) in patients with CD and evaluate the long-term efficacy of mirikizumab on clinical remission and endoscopic response in patients with EIMs at baseline.

Methods
Patients randomized to receive mirikizumab (N=579) or placebo (N=199) in the VIVID-1 study were included. Among patients with at least 1 EIM at baseline, we evaluated EIM resolution, clinical remission, and endoscopic response at week (W) 52. Onset of new EIMs was assessed among patients with no EIMs at baseline. Prespecified analyses included EIM resolution and onset of new EIMs, while post hoc analyses included clinical remission and endoscopic response among patients with EIMs at baseline. Categorical endpoints were analysed using the Cochran–Mantel–Haenszel test, with missing values imputed by non-responder imputation.

Results
Of 778 patients in the mirikizumab and placebo arms of VIVID-1, 173 (22.2%) had ≥1 EIM at baseline, primarily arthritis or arthralgia. Baseline demographics and disease characteristics were similar between patients with EIMs at baseline and those in the overall population, except for a numerically higher proportion of female patients with EIMs at baseline (Table 1). At W12, a numerically higher proportion of mirikizumab-treated versus placebo-treated patients showed EIM resolution (46.2% vs 31.7%; P=0.113). Through W52, the EIM resolution rate with mirikizumab improved to 56.8%. The proportion of patients who achieved both clinical response by Patient Reported Outcome at W12 and EIM resolution at W52 was significantly higher for mirikizumab compared to placebo (43.2% vs 14.6%; P&lt;0.0001)(Fig. 1). In addition, among patients with EIMs at baseline, higher proportions of mirikizumab-treated patients than placebo-treated patients achieved (1) clinical response at W12 and clinical remission at W52 (39.4% vs 19.5%; P&lt;0.024) and (2) clinical response at W12 and endoscopic remission at W52 (36.4% vs 4.9%; P=0.0002). The rate of new-onset EIMs at W52 was low among all patients treated with mirikizumab or placebo (1.8% vs 1.9%; P=0.847).

Conclusion
Treatment with mirikizumab led to higher rates of EIM resolution at W52 compared to placebo. Response rates for clinical and endoscopic outcomes were similar between patients with EIMs at baseline and the overall population in VIVID-1.1

References
1.Ferrante, et al., (in press, 2024) Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn’s disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study