Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Crohn's Disease.

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.

• Authors: Bruce E Sands, Laurent Peyrin-Biroulet, Jaroslaw Kierkus, Peter D R Higgins, Monika Fischer, Vipul Jairath, Fumihito Hirai, Geert D'Haens, Ruth M Belin, Debra Miller, Elisa Gomez-Valderas, April N Naegeli, Jay L Tuttle, Paul F Pollack, William J Sandborn
• Journal: Gastroenterology (Gastroenterology) Vol. 162 Issue 2 Pg. 495-508 (02 2022) ISSN: 1528-0012 [Electronic] United States
• PMID: 34748774 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Antibodies, Monoclonal, Humanized
• Gastrointestinal Agents
• Interleukin-23 Subunit p19
• mirikizumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Crohn Disease (drug therapy, pathology, physiopathology)
• Endoscopy, Digestive System
• Female
• Gastrointestinal Agents (therapeutic use)
• Humans
• Induction Chemotherapy
• Interleukin-23 Subunit p19 (antagonists & inhibitors)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Patient Reported Outcome Measures
• Remission Induction
• Severity of Illness Index
• Treatment Outcome