Bowel Urgency in Crohn's Disease: Effects of Mirikizumab in a Randomized Controlled Phase 3 Study

Background and Aims: Bowel urgency (BU) is an underrecognized and debilitating symptom of Crohn's disease. Mirikizumab, an interleukin-23p19 inhibitor, is efficacious for BU resolution in ulcerative colitis. We evaluated the efficacy of mirikizumab in achieving early BU response and remission among participants with Crohn's disease enrolled in the phase 3 VIVID-1 study. The associations of disease characteristics with baseline BU and BU resolution were explored. Methods: Adult participants were randomized to receive mirikizumab or placebo. BU was assessed using the Urgency Numeric Rating Scale (NRS) (range 0–10) at baseline, and every 4 weeks. The proportion of participants with baseline Urgency NRS ≥3 and ≥6 who achieved BU clinically meaningful improvement (CMI) (≥3 change in Urgency NRS) and BU remission (Urgency NRS ≤2) was calculated, and associations of BU CMI and BU remission with clinical outcomes were assessed. Results: At baseline, 94.2% of participants had an Urgency NRS score ≥3. BU positively correlated with the Crohn's Disease Activity Index and abdominal pain. Improvement in BU from baseline was significantly greater in mirikizumab-treated participants as early as week 6 and sustained to week 52 vs patients receiving placebo. Participants treated with mirikizumab achieved significantly higher rates of BU CMI and BU remission at weeks 12 and 52 vs placebo. Mirikizumab-treated participants who achieved BU CMI at week 12 had better clinical and endoscopic outcomes at weeks 12 and 52. Conclusions: Mirikizumab-treated participants achieved significantly higher rates of BU CMI and remission at weeks 12 and 52, which was associated with better short- and longer-term clinical outcomes. ClinicalTrials.gov,