Efficacy and Safety of Mirikizumab in Patients With Crohn's Disease: 104-Week Extension Results From a Phase 2 Randomized Controlled Trial

Introduction: Here we report efficacy and safety of mirikizumab (miri) up to Week 104 in patients with moderately-to-severely active Crohn’s disease (CD). Methods: At baseline, pts (N=191) were randomized 2:1:1:2 to 4 treatment arms (1000, 600, 200mg miri and placebo (PBO), intravenously (IV) every 4 weeks (Q4W) at W0, W4, and W8). Pts who received miri and achieved ≥1 point improvement in Simple Endoscopic Score for Crohn’s Disease (SES-CD) at W12 were rerandomized 1:1 into double-blind maintenance to either continue IV treatment Q4W (IV-C; N=41) or 300mg miri subcutaneous (SC) Q4W (IV-SC; N=46) up to W52. W12 endoscopic non-improvers and pts receiving PBO during induction received IV 1000mg miri Q4W from W12-W52. Subjects reported to experience clinical benefit received 300 mg SC from W52 to W104. All IV and SC arms were pooled for analysis. Results: Overall, 68.5% (87/127) achieved endoscopic improvement at W12 and were rerandomized into maintenance. Of the W12 endoscopic improvers, 74 finished W52 maintenance and entered the extension period (W52-W104) where 68 completed treatment through W104. Among W12 miri induction endoscopic improvers, Crohn’s Disease Activity Index (CDAI) remission rates (CDAI Total Score < 150) were 39.0% (16/41) (IV-C) and 56.5% (26/46)(SC) and PRO remission (defined as SF ≤2.5 and AP ≤1 and no worse than baseline) rates were 46.3% (19/41)(IV-C) and 45.7% (21/46)(SC) at W52. At W104, CDAI remission rates were 66.7% (22/33)(IV-C) and 61.0% (25/41)(SC) and PRO remission rates were 63.6% (21/33)(IV-C) and 46.3% (19/41)(SC). Of the 74 endoscopic improvers who finished W52 maintenance, 6 discontinued between W52 to W104 (1 due to adverse events (AEs), 2 due to lack of efficacy, 1 due to lost to follow-up, and 2 due to withdrawal by subject). Among endoscopic improvers at W12, 4 pts were hospitalized due to CD in the SC group (2 from W12-W52 and 2 from W52-W104) as reported in Table 1. In all pts who received any miri treatment from W52 to W104 (endoscopic improvers, non-improvers, and PBO treated pts), 79.4% (108/136) experienced ≥ 1 treatment-emergent AEs. Conclusion: Miri demonstrated durable effectiveness among pts with moderately-to-severely active CD who showed early endoscopic improvement with continued miri dosing up to W104, and with no unexpected safety events. CDAI and PRO remission were sustained through W104, with no differences observed in pts who received either IV-C and SC miri treatments during maintenance and continued into the extension period. Table 1. - Week 52 and Week 104 Safety and Efficacy Results in Week 12 endoscopic improvers Week 12 Endoscopic Improvers Week 52 Week 104 Week 52 Week 104 Miri IV-CN=41 Miri IV-CN=33 Miri SCN=46 Miri SCN=41 PRO remissiona, n (%) 19 (46.3) 21 (63.6) 21 (45.7) 19 (46.3) CDAI remissionb, n (%) 16 (39.0) 22 (66.7) 26 (56.5) 25 (61.0) Hospitalization events due to CD, n (%) 0 (0) 0 (0) 2 (4.3) 2 (4.9) aPRO remission: defined as SF ≤2.5 and AP ≤1, and no worse than baseline.bCDAI remission: A CDAI score of < 150 points.cEndoscopic improvement: ≥1 point improvement in SES-CD at Week 12.Abbreviations: CD = Crohn’s disease; SF = stool frequency; AP = abdominal pain; CDAI = Crohn’s Disease Activity Index; PRO = patient-reported outcomes.