Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis.

Autor:	Sandborn WJ; University of California San Diego, La Jolla, California. Electronic address: wsandborn@ucsd.edu., Ferrante M; Department of Gastroenterology and Hepatology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Leuven, Belgium., Bhandari BR; Delta Research Partners, Bastrop, Louisiana., Berliba E; Nicolae Testemitanu State University of Medicine, Arsenia Exploratory Medicine, Chisinau, Moldova., Feagan BG; Western University, Robarts Clinical Trials Inc, London, Ontario, Canada., Hibi T; Kitasato Institute Hospital Center for Advanced Inflammatory Bowel Disease Research and Treatment, Minato-ku, Tokyo, Japan., Tuttle JL; Eli Lilly and Company, Lilly Biotechnology Center, San Diego, California., Klekotka P; Eli Lilly and Company, Lilly Biotechnology Center, San Diego, California., Friedrich S; Eli Lilly and Company, Indianapolis, Indiana., Durante M; Eli Lilly and Company, Indianapolis, Indiana., Morgan-Cox M; Eli Lilly and Company, Indianapolis, Indiana., Laskowski J; Eli Lilly and Company, Lilly Biotechnology Center, San Diego, California., Schmitz J; Eli Lilly and Company, Indianapolis, Indiana., D'Haens GR; Amsterdam University Medical Centers, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2020 Feb; Vol. 158 (3), pp. 537-549.e10. Date of Electronic Publication: 2019 Sep 04.
DOI:	10.1053/j.gastro.2019.08.043
Abstrakt:	Background & Aims: Interleukin 23 contributes to the pathogenesis of ulcerative colitis (UC). We investigated the effects of mirikizumab, a monoclonal antibody against the p19 subunit of interleukin 23, in a phase 2 study of patients with UC. Methods: We performed a trial of the efficacy and safety of mirikizumab in patients with moderate to severely active UC, enrolling patients from 14 countries from January 2016 through September 2017. Patients were randomly assigned to groups given intravenous placebo (N = 63), mirikizumab 50 mg (N = 63) or 200 mg (N = 62) with exposure-based dosing, or mirikizumab 600 mg with fixed dosing (N = 61) at weeks 0, 4, and 8. Of assigned patients, 63% had prior exposure to a biologic agent. Clinical responders (decrease in 9-point Mayo score, including ≥2 points and ≥35% from baseline with either a decrease of rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1) at week 12 who had received mirikizumab were randomly assigned to groups that received maintenance treatment with mirikizumab 200 mg subcutaneously every 4 weeks (N = 47) or every 12 weeks (N = 46). The primary endpoint was clinical remission (Mayo subscores of 0 for rectal bleeding, with 1-point decrease from baseline for stool frequency, and 0 or 1 for endoscopy) at week 12. A multiple testing procedure was used that began with the 600-mg dose group, and any nonsignificant comparison result ended the formal statistical testing procedure. Results: At week 12, 15.9% (P = .066), 22.6% (P = .004), and 11.5% (P = .142) of patients in the 50-mg, 200-mg, and 600-mg groups achieved clinical remission, respectively, compared with 4.8% of patients given placebo. The primary endpoint was not significant (comparison to 600 mg, P > .05). Clinical responses occurred in 41.3% (P = .014), 59.7% (P < .001), and 49.2% (P = .001) of patients in the 50-mg, 200-mg, and 600-mg groups, respectively, compared with 20.6% of patients given placebo. At week 52, 46.8% of patients given subcutaneous mirikizumab 200 mg every 4 weeks and 37.0% given subcutaneous mirikizumab 200 mg every 12 weeks were in clinical remission. Conclusions: In a randomized trial of patients with UC, mirikizumab was effective in inducing a clinical response after 12 weeks. Additional studies are required to determine the optimal dose for induction of remission. Mirikizumab showed durable efficacy throughout the maintenance period. Clinicaltrials.gov, Number NCT02589665. (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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