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

Author information

¹Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: bruce.sands@mssm.edu.

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.

PMID: 34748774

DOI: 10.1053/j.gastro.2021.10.050

Abstract

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.