P73 Effect of mirikizumab on bowel urgency clinically meaningful improvement and remission: phase 3 LUCENT induction and maintenance study results

IntroductionBowel urgency (BU; sudden or immediate need to have a bowel movement) is a common and burdensome symptom for patients with ulcerative colitis (UC). BU was assessed in mirikizumab (miri; an IL-23p19inhibitor) Phase 3 LUCENT studies in moderately to severely active UC (NCT03518086, NCT03524092) using the validated Urgency Numeric Rating Scale (UNRS). UNRS measures BU severity in the past 24 hours from 0 (no urgency) to 10 (worst possible urgency). Psychometric evaluation of the UNRS showed Clinically Meaningful Improvement (CMI) is ≥3 point change; Remission is a score of 0 or 1. This analysis evaluated the proportions of patients in LUCENT studies achieving BU CMI and BU remission.MethodsThe modified intent-to-treat (mITT) population (patients receiving ≥1 dose of miri or placebo (PBO); N= 1281) was randomized at induction study baseline in a 3:1 ratio to IV doses of 300mg miri or PBO every 4 weeks (Q4W) during induction (W0, 4, and 8). Patients achieving Clinical Response, measured by Modified Mayo Score (MMS), to miri during induction were re-randomized at W0 of the maintenance study in a 2:1 ratio to subcutaneous (SC) 200mg miri or PBO Q4W through W40 (52 weeks of treatment). Patients recorded their UNRS score daily in an e-diary. Mean weekly UNRS scores were calculated from diary data if ≥4 days of data were available. Rates of BU CMI and BU remission in the miri v PBO groups were compared at W12 (induction) in the mITT population with a baseline UNRS score ≥3, and W52 (maintenance) among miri clinical responders at W12 with a baseline UNRS score ≥3. Cochran-Mantel-Haenszel tests with non-responder imputation for missing values were used for all treatment comparisons.ResultsPatient population: mean age 43 years, 60% male, disease duration 7 years; 63.0% left-sided colitis; 36.3% pancolitis; 46.7% moderate disease (MMS 4–6); 53.2% severe disease (MMS 7–9). Significantly higher proportions of miri versus PBO patients achieved BU CMI (48.7% v 32.2%) and BU remission (22.1% v 12.3%) at W12 (both p