Gastroenterology. 2021 Nov 5:S0016-5085(21)03725-2. doi: 10.1053/j.gastro.2021.10.050. Online ahead of print.
BACKGROUND: Mirikizumab is a humanized monoclonal antibody targeting IL-23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD).
METHODS: Patients (N=191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000mg mirikizumab, administered intravenously (IV) every 4 weeks (Q4W). Patients who received mirikizumab and achieved ≥1 point improvement in SES-CD at Week 12 (Re-randomized Maintenance Cohort) were re-randomized to continue their induction IV treatment (IV-C) or receive 300mg mirikizumab subcutaneously (SC) Q4W. Non-randomized Maintenance Cohort included endoscopic non-improvers (NI/1000mg) and PBO patients (PBO/1000mg) who received 1000mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in SES-CD) at Week 12.
RESULTS: At Week 12, endoscopic response was significantly higher by the pre-defined 2-sided significance level of 0.1 for all mirikizumab groups compared to PBO (200mg: 25.8%, 8/31[95%CI: 10.4-41.2], p=0.079; 600mg: 37.5%, 12/32[95%CI: 20.7-54.3], p=0.003; 1000mg: 43.8%, 28/64[95%CI: 31.6-55.9], p<0.001; PBO: 10.9 %, 7/64[95%CI: 3.3-18.6]). Endoscopic response at Week 52 was 58.5%(24/41) and 58.7%(27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in mirikizumab groups were similar to PBO. Through Week 52, frequencies of TEAEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the Non-randomized Maintenance Cohort.
CONCLUSION: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52.