S16 Association of Quality of Life With Clinical Remission, HEMR, and Bowel Urgency in Patients With Ulcerative Colitis Treated With Mirikizumab

Abstract

Background: Mirikizumab, a p19-directed anti-IL-23 antibody, has demonstrated efficacy and safety in patients with moderately-to-severely active ulcerative colitis (UC) in the Phase 3 LUCENT-1 induction trial (NCT03518086) and LUCENT-2 maintenance trial (NCT03524092). Secondary analyses of LUCENT trials showed that mirikizumab treated patients had significantly improved quality of life compared to patients with placebo. This analysis evaluated the relationships between quality of life assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) and patients’ status of achieving clinical remission, histologic-endoscopic mucosal remission (HEMR), bowel urgency clinically meaningful improvement (CMI), and bowel urgency remission. Methods: In LUCENT-1, 1,281 patients were randomized 3:1 to mirikizumab 300 mg intravenous infusion or placebo every 4 weeks (Q4W). Patients who achieved clinical response to mirikizumab by Week 12 (W12) of induction (N=544), were re-randomized 2:1 to subcutaneous mirikizumab 200mg or placebo Q4W for 40 weeks in LUCENT-2 (52-weeks of continuous treatment). The primary endpoint was proportion of patients with clinical remission at W12 in LUCENT-1 and Week 40 in LUCENT-2. The clinical outcomes of interest in this analysis include: IBDQ (a 32-item patient-completed questionnaire with higher scores indicating better disease-specific quality of life ), clinical remission (stool frequency subscore = 0 or 1 with a ≥1-point decrease from baseline; rectal bleeding subscore = 0; and endoscopic subscore (ES)= 0 or 1), HEMR (Geboes score of ≤2B and ES = 0 or 1), and bowel urgency [assessed using the Urgency Numeric Rating Scale (UNRS), a 11-point scale ranging from 0 (“no urgency”) to 10 (“worst possible urgency”)]. Bowel urgency CMI is a ≥3-point change and bowel urgency remission is a UNRS score of 0 or 1, both among patients with a baseline UNRS of ≥3. Association between IBDQ total score change from baseline and clinical outcomes were assessed at W12 and Week 52 (W52) using analysis of covariance models adjusting for treatment, clinical parameter, baseline IBDQ value, and randomization stratification factors. Results: Overall, significantly greater increase in IBDQ total score were observed in patients who achieved clinical remission, HEMR, bowel urgency CMI or bowel urgency remission compared to those who did not. As for patients treated with mirikizumab, the least square mean (LSM) change of IBDQ total score [LSM(SE)] by clinical outcome status (Yes vs No) were: Clinical Remission: W12: 55.0 (2.02) vs 33.7 (1.16), P< 0.001; W52: 60.7 (2.38) vs 39.8 (2.43), P< 0.001; HEMR: W12: 50.3 (2.15) vs 35.2 (1.19), P< 0.001; W52: 59.3 (2.60) vs 43.4 (2.40), P< 0.001; Bowel Urgency CMI: W12: 52.8 (1.41) vs 27.4 (1.36), P< 0.001; W52: 62.5 (2.20) vs 34.4 (2.77), P< 0.001; and Bowel Urgency Remission: W12: 57.6 (1.92) vs 32.3 (1.15), P< 0.001; W52: 64.9 (2.54) vs 40.8 (2.18), P< 0.001. Placebo-treated patients were similar to the mirikizumab group across the studied clinical outcomes endpoints, with smaller magnitude of IBDQ improvements. Conclusion(s): The achievement of clinical remission, histologic-endoscopic mucosal remission, bowel urgency clinically meaningful improvement and bowel urgency remission was associated with significant improvement in quality of life by IBDQ in patients with UC from LUCENT-1 and 2 trials.