- Fecal Incontinence
|Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease
Gastroenterology. 2022 Feb;162(2):495-508. doi: 10.1053/j.gastro.2021.10.050.Epub 2021 Nov 5.
Bruce E Sands 1, Laurent Peyrin-Biroulet 2, Jaroslaw Kierkus 3, Peter D R Higgins 4, Monika Fischer 5, Vipul Jairath 6, Fumihito Hirai 7, Geert D'Haens 8, Ruth M Belin 9, Debra Miller 9, Elisa Gomez-Valderas 9, April N Naegeli 9, Jay L Tuttle 9, Paul F Pollack 9, William J Sandborn 10
1Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: email@example.com.
2University Hospital of Nancy, Vandoeuvre-les-Nancy, France.
3Children's Memorial Health Institute, Warsaw, Poland.
4University of Michigan, Ann Arbor, Michigan.
5Indiana University, Indianapolis, Indiana.
6Western University, London, Canada.
7Fukuoka University, Fukuoka, Japan.
8Amsterdam University Medical Centers, Amsterdam, the Netherlands.
9Eli Lilly and Company, Indianapolis, Indiana.
10University California San Diego, La Jolla, California.
Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 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 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 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg 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 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 PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4-41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7-54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6-55.9, P < .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 the mirikizumab groups were similar to PBO. 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 nonrandomized 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. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226.