Impact of Mirikizumab Treatment on Fatigue in Patients with Moderately to Severely Active Crohn's Disease: Results from the Phase 3 VIVID-1 Study.

BackgroundFatigue is a debilitating multifactorial symptom experienced by patients with Crohn's disease. Mirikizumab, an anti-interleukin-23p19 antibody, demonstrated significant efficacy and safety in the patients with moderately to severely active Crohn's disease. This analysis investigated the impact of mirikizumab on fatigue and the association between changes in clinical, endoscopic, and patient-reported outcomes with improvement in fatigue from baseline in the Phase 3 VIVID-1 study.MethodsAdult patients with moderately to severely active Crohn's disease that failed at least 1 biologic agent or conventional therapy were randomized to receive mirikizumab or placebo. Fatigue was assessed via the validated Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire. Fatigue associations with patient-reported outcomes, endoscopic, and clinical measures were assessed via Pearson correlation analysis.ResultsAt Week 12, 43% and 33%, and at Week 52, 46% and 36%, of mirikizumab-treated patients achieved ≥6 and ≥9 fatigue score improvements versus placebo (Week 12, 31%, 22%; Week 52, 20%, 16%), respectively. Baseline fatigue scores were strongly associated with depressive symptoms and moderately associated with quality-of-life at baseline. Improvements in fatigue at Weeks 12 and 52 were strongly associated with quality-of-life and patient-reported outcomes and weakly with objective markers of inflammation and disease activity.ConclusionsMirikizumab-treated patients with Crohn's disease achieved higher rates of clinically meaningful improvement in fatigue versus placebo at Weeks 12 and 52, which correlated with improvement in clinical and patient-reported outcomes. Baseline fatigue severity was strongly associated with depressive symptoms in VIVID-1 (NCT03926130).