Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis.
Publication/Presentation Date
6-29-2023
Abstract
BACKGROUND: Mirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.
METHODS: We conducted two phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab in adults with moderately to severely active ulcerative colitis. In the induction trial, patients were randomly assigned in a 3:1 ratio to receive mirikizumab (300 mg) or placebo, administered intravenously, every 4 weeks for 12 weeks. In the maintenance trial, patients with a response to mirikizumab induction therapy were randomly assigned in a 2:1 ratio to receive mirikizumab (200 mg) or placebo, administered subcutaneously, every 4 weeks for 40 weeks. The primary end points were clinical remission at week 12 in the induction trial and at week 40 (at 52 weeks overall) in the maintenance trial. Major secondary end points included clinical response, endoscopic remission, and improvement in bowel-movement urgency. Patients who did not have a response in the induction trial were allowed to receive open-label mirikizumab during the first 12 weeks of the maintenance trial as extended induction. Safety was also assessed.
RESULTS: A total of 1281 patients underwent randomization in the induction trial, and 544 patients with a response to mirikizumab underwent randomization again in the maintenance trial. Significantly higher percentages of patients in the mirikizumab group than in the placebo group had clinical remission at week 12 of the induction trial (24.2% vs. 13.3%, P
CONCLUSIONS: Mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active ulcerative colitis. Opportunistic infection or cancer occurred in a small number of patients treated with mirikizumab. (Funded by Eli Lilly; LUCENT-1 and LUCENT-2 ClinicalTrials.gov numbers, NCT03518086 and NCT03524092, respectively.).
Volume
388
Issue
26
First Page
2444
Last Page
2455
ISSN
1533-4406
Published In/Presented At
D'Haens, G., Dubinsky, M., Kobayashi, T., Irving, P. M., Howaldt, S., Pokrotnieks, J., Krueger, K., Laskowski, J., Li, X., Lissoos, T., Milata, J., Morris, N., Arora, V., Milch, C., Sandborn, W., Sands, B. E., & LUCENT Study Group (2023). Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. The New England journal of medicine, 388(26), 2444–2455. https://doi.org/10.1056/NEJMoa2207940
Disciplines
Medicine and Health Sciences
PubMedID
37379135
Department(s)
Department of Medicine
Document Type
Article