Effect of 104 Weeks of Mirikizumab Treatment on Inflammatory Bowel Disease Questionnaire Scores Among Patients With Moderately to Severely Active Crohn's Disease

Introduction: Mirikizumab (miri) is an anti-IL23p19 antibody that has shown efficacy in Crohn’s disease (CD). We have previously shown that miri improves health-related quality of life (HRQoL) by 12 weeks as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) in a Phase 2, multicenter, randomized, double-blind, placebo (PBO)-controlled study (NCT02891226) conducted in patients (pts) with moderately-to-severely active CD. This analysis assesses IBDQ scores through Week 104 (W104). Methods: At baseline, pts (N=191) were randomized 2:1:1:2 allocation amongst 4 treatment arms (PBO, and 200, 600, 1000mg miri, respectively, administered intravenously (IV) every 4 weeks (Q4W) at Weeks 0, 4, and 8). Pts who received miri and achieved ≥1 point improvement at W12 in Simple Endoscopic Score for Crohn’s Disease (SES-CD) were re-randomized 1:1 into double-blind maintenance to either continue IV treatment assignment Q4W (combined arms of 200, 600, and 1000mg miri IV treatment; IV-C; N=41) or to 300mg miri subcutaneous (SC; N=46) Q4W up to W52. Subjects who had clinical benefit from the maintenance period received 300mg SC Q4W from W52 to W104. For analysis purposes, all IV and all SC arms were pooled. IBDQ score change from baseline (BL), IBDQ response (improvement ≥16 points), and IBDQ remission (score ≥170 points) were assessed up to W104 in pts who achieved endoscopic improvement at W12. Results: Out of the 127 pts randomized to miri for induction, 68.5% (87/127) achieved endoscopic improvement at W12 and were rerandomized into maintenance. Among the W12 miri induction endoscopic improvers, IBDQ response rates at W52 were 75.6% (31/41) and 80.4% (37/46) and IBDQ remission rates were 65.9% (27/41) and 67.4% (31/46) in the IV-C and SC groups, respectively. Of the W12 endoscopic improvers, 74 finished W52 in the maintenance and entered period 3 (W52-W104) where 68 went on to complete treatment through W104. At W104, the IBDQ response rates were 81.8% (27/33) and 78.0% (32/41) and IBDQ remission rates were 69.7% (23/33) and 56.1% (23/41) in the IV-C and SC groups, respectively. W52 and W104 IBDQ outcomes and domain scores are reported in Table 1. Conclusion: Treatment with miri produced clinically meaningful improvement in HRQoL as measured by IBDQ at W52 and W104 in pts who achieved endoscopic improvement after miri induction with moderately-to-severely active CD. Table 1. - Week 52 and Week 104 IBDQ Outcomes in miri induction Week 12 Endoscopic Improvers Week 12 Endoscopic Improverse Week 52 Week 104 Week 52 Week 104 Miri IV-CN=41 Miri IV-CN=33 Miri SCN=46 Miri SCN=41 Total IBDQ scorea, mean (SD) 188.5 (26.6) 187.4 (21.8) 180.8 (25.4) 173.7 (32.1) IBDQ responseb, n (%) 31 (75.6) 27 (81.8) 37 (80.4) 32 (78.0) IBDQ remissionc, n (%) 27 (65.9) 23 (69.7) 31 (67.4) 23 (56.1) IBDQ score change from baseline a d mean 64.3 67.1 66.4 57.9 IBDQ Domain Scoresa, mean (SD) Bowel symptoms 58.6 (8.8) 58.8 (6.5) 57.3 (8.0) 54.3 (9.8) Systemic symptoms 27.7 (5.4) 26.8 (5.1) 25.8 (5.4) 24.7 (6.6) Emotional function 70.5 (11.1) 70.0 (9.9) 67.1 (11.0) 65.0 (13.1) Social function 31.8 (3.9) 31.8 (3.34) 30.6 (4.2) 29.7 (5.3) aMean and (SD) for scores and changes in scores do not utilize imputation and therefore are based on patients with observed data at the indicated timepoint (IV week 52 N=35; IV week 104 N=29; SC week 52 N=41; SC week 104 N=33).bIBDQ response: ≥16-point improvement in IBDQ score.cIBDQ remission: total IBDQ score ≥170.dChange from baseline.eEndoscopic improvement: ≥1 point improvement in SES-CD at Week 12.Abbreviations: IBDQ = Inflammatory Bowel Disease Questionnaire; IV-C = Intravenous arms combined; SC = subcutaneous; SD = standard deviation.