S0705 Evaluation of Symptom Improvement During Induction in Patients With Crohn's Disease Treated With Mirikizumab

Abstract

INTRODUCTION: Mirikizumab (miri), a humanized, IgG4 monoclonal antibody that targets IL23, has shown efficacy and safety in patients treated for Crohn's disease (CD), psoriasis, and ulcerative colitis. In a phase 2, randomised, parallel-arm, placebo-controlled study, symptom improvement was evaluated in patients with moderately-to-severely active CD after intravenous induction treatment with miri (NCT02891226). METHODS: Entry criteria for enrollment included an average daily stool frequency (SF; ≥ 4) and/or the average daily occurrence of abdominal pain (AP; ≥ 2) from the Crohn's Disease Activity Index (CDAI), and a Simple Endoscopic Score for CD ≥ 7 in patients with ileal-colonic or ≥ 4 in patients with isolated ileal disease. Patients were randomised 2:1:1:2 to receive intravenous miri (200 mg, 600 mg, or 1,000 mg) or placebo at weeks 0, 4, and 8. Endpoints in this analysis included changes from baseline in CDAI, SF, and AP at weeks 4, 8, and 12. A mixed effects model for repeated measures analysis was conducted to compare mean changes from baseline across treatment groups for the all-patient cohort and for the biologic-experienced sub-group. Factors in the analysis included treatment, geographic region, baseline score, prior biologic CD therapy (all-patient cohort), visit, and treatment by visit interaction as fixed effects. An unstructured variance covariance was used. RESULTS: A total of 191 patients were randomised at baseline, which included biologic naïve (n = 71) and biologic-experienced patients (n = 120). Changes in CDAI, SF, AP at weeks 4, 8 and 12 compared to baseline are shown in the Table. In the all-patient cohort, statistically significant improvement in CDAI was observed with miri 600 mg and in SF with miri 200 mg compared to placebo as early as week 4 (Table). Improvement in CDAI and SF occurred with all miri doses (200 mg, 600 mg, 1,000 mg) at weeks 8 and 12 and in AP at weeks 8 and 12 with all miri doses. Compared to placebo, the subgroup of biologic-experienced patients showed statistically significant improvement in CDAI at week 4 (miri 600 mg) and at weeks 8 and 12 with all three doses. Further, significant improvement was observed in SF at week 12 (miri 600 mg and miri 1,000 mg) and in AP at week 8 (miri 600 mg) and week 12 (miri 600 mg and miri 1,000 mg). CONCLUSION: Treatment with miri induced early improvement in clinical symptoms and disease activity in patients with moderately-to-severely active CD.Table 1: Treatment Effect of Mirikizumab vs Placebo in Reducing Crohn's Disease Activity Index, Stool Frequency, and Abdominal Pain Over Time