• Geert D'Haens, Marla Dubinsky, Taku Kobayashi, Peter M Irving, Stefanie Howaldt, Juris Pokrotnieks, Kathryn Krueger, Janelle Laskowski, Xingyuan Li, Trevor Lissoos, Joe Milata, Nathan Morris, Vipin Arora, Catherine Milch, William Sandborn, Bruce E Sands, and LUCENT Study Group.
• From the Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam (G.D.); Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York (M.D., B.E.S.); the Center for Advanced IBD Research and Treatment, Kitasato University, Kitasato Institute Hospital, Tokyo (T.K.); Guy's Hospital, St. Thomas' Hospital, and the School of Immunology and Microbial Sciences, King's College London - all in London (P.M.I.); Research Institute for IBD-HaFCED, Hamburg, Germany (S.H.); Riga Stradins University, Riga, Latvia (J.P.); Eli Lilly, Indianapolis (K.K., J.L., X.L., T.L., J.M., N.M., V.A., C.M.); and the University of California San Diego, La Jolla (W.S.).
• N. Engl. J. Med. 2023 Jun 29; 388 (26): 244424552444-2455.

BackgroundMirikizumab, a p19-directed antibody against interleukin-23, showed efficacy in the treatment of ulcerative colitis in a phase 2 trial.MethodsWe 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.ResultsA 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<0.001) and at week 40 of the maintenance trial (49.9% vs. 25.1%, P<0.001). The criteria for all the major secondary end points were met in both trials. Adverse events of nasopharyngitis and arthralgia were reported more frequently with mirikizumab than with placebo. Among the 1217 patients treated with mirikizumab during the controlled and uncontrolled periods (including the open-label extension and maintenance periods) in the two trials, 15 had an opportunistic infection (including 6 with herpes zoster infection) and 8 had cancer (including 3 with colorectal cancer). Among the patients who received placebo in the induction trial, 1 had herpes zoster infection and none had cancer.ConclusionsMirikizumab 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.).Copyright © 2023 Massachusetts Medical Society.

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