Esophagus to Small Intestine
Gastroenterology. 2022;162(2):495–508
Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Crohn’s disease
Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. The authors 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, 200 mg, 600 mg, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥ 1-point improvement in Simple Endoscopic Score-CD at week 12 (re-randomized maintenance cohort) were re-randomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Non-randomized maintenance cohort included endoscopic non-improvers (1000 mg) and placebo patients (placebo/1000 mg) who received 1000 mg mirikizumab IV from week 12. The primary objective was to evaluate superiority of mirikizumab to placebo in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at week 12.
Results: At week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with placebo (200 mg: 25.8%, 8/31, 95% confidence interval [CI]: 10.4–41.2, p = 0.079; 600 mg: 37.5%, 12/32, 95% CI: 20.7–54.3, p = 0.003; 1000 mg: 43.8%, 28/64, 95% CI: 31.6–55.9, p < 0.001; placebo: 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 the mirikizumab groups were similar to placebo. Through week 52, frequencies of treatment-emergent AEs 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 Crohn’s disease and demonstrated durable efficacy to week 52.