Mirikizumab Sustains Improvement on Health-Related Quality of Life in Patients With Crohn's Disease at Week 104: A Phase 2 Study Analysis Using the SF-36

Introduction: Mirikizumab (miri) treatment improved quality of life in patients with moderately-to-severely active Crohn’s disease (CD) through Week 52 (W52) as assessed by Medical Outcomes 36-Item Short Form Health Survey (SF-36) scores in the Phase 2 randomized, double-blind, parallel, placebo (PBO)-controlled study (SERENITY/NCT02891226). Here we evaluated the effect of miri on quality of life up to W104. Methods: Patients (N=191) were randomized 2:1:1:2 allocation across 4 treatment arms (PBO, 200, 600, and 1000mg miri, administered intravenously (IV) every 4 weeks (Q4W) at W0, W4, and W8). Patients who received miri and achieved ≥1 point improvement in Simple Endoscopic Score for Crohn’s Disease (SES-CD) at W12 (Improvers) were rerandomized 1:1 into double-blind maintenance to either continue IV treatment assignment Q4W (IV-C) or to 300mg miri subcutaneous (SC) Q4W (IV-SC) up to W52. Subjects with clinical benefit from the maintenance period received 300mg SC Q4W from W52-W104 (open-label extension period). SF-36 Physical (PCS) and Mental (MCS) Component Summary, and 8 domain scores (physical functioning, role-physical, role-emotional, bodily pain, vitality, social functioning, mental and general health) were evaluated up to W104 and summarized by randomized treatment (i.e. pooled all IV and all SC) from W12-52 among endoscopic improvers at W12 who were rerandomized into maintenance and went onto the extension period. Results: Of the 127 patients randomized to miri for induction, 68.5% (87/127) achieved endoscopic improvement at W12 and were rerandomized into maintenance. Of the 87 W12 endoscopic improvers, 74 finished W52 maintenance and entered the extension period (W52-W104) where 68 went on to complete treatment through W104. Although statistical comparisons were not made between groups during the maintenance and extension periods, comparison of mean changes from baseline in PCS, MCS, and domain scores suggest that improvements at W52 were sustained or further numerically increased with miri extension treatment (W52-W104) in the IV-C group. PCS, MCS, and domain scores are reported in Table 1. Conclusion: Treatment with miri is associated with a sustained improvement in quality of life as measured by SF-36 from W52 to W104 in patients with moderately-to-severely active CD. Table 1 - Observed mean CFBL, (SD) Week 12 Endoscopic Improvers a Week 52 Week 104 Week 52 Week 104 Miri IV-CN=35 Miri IV-CN=29 Miri SCN=41 Miri SCN=38 PCS 10.47 (8.72) 11.68 (6.60) 10.70 (7.88) 9.96 (8.17) MCS 8.49 (11.30) 9.32 (12.35) 11.45 (11.42) 10.43 (11.59) Domain Scores Physical functioning 17.29 (18.48) 19.14 (17.17) 22.93 (22.30) 22.37 (22.83) Role-physical 30.89 (24.95) 32.33 (20.87) 32.01 (28.24) 26.64 (29.27) Role-emotional 13.10 (25.59) 16.95 (26.12) 22.36 (21.36) 19.96 (22.39) Bodily pain 27.20 (29.04) 35.28 (23.86) 34.61 (25.30) 31.00 (27.87) Vitality 28.04 (27.39) 26.72 (29.41) 30.79 (26.16) 29.11 (26.17) Social functioning 29.29 (29.85) 31.90 (24.91) 31.10 (24.71) 25.99 (30.26) Mental health 15.57 (20.39) 17.76 (23.59) 21.83 (23.63) 20.79 (22.74) General health 23.91 (20.38) 26.28 (21.70) 21.02 (18.31) 22.55 (18.38) aEndoscopic improvement: ≥1 point improvement in SES-CD at Week 12.Abbreviations: CFBL = change from baseline; SD = standard deviation; PCS = Physical Component Summary; MCS = Mental Component Summary; IV-C = all IV-IV miri groups pooled; SC = all IV-subcutaneous miri groups pooled.