1. Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis
- Author
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Michael Durante, Jochen Schmitz, Stuart Friedrich, Elina Berliba, Jay Tuttle, Toshifumi Hibi, Bal R. Bhandari, Janelle Laskowski, Marc Ferrante, William J. Sandborn, MaryAnn Morgan-Cox, Geert R. D'Haens, Brian G. Feagan, Paul Klekotka, Gastroenterology and Hepatology, and AGEM - Digestive immunity
- Subjects
0301 basic medicine ,Male ,Phases of clinical research ,Gastroenterology ,Severity of Illness Index ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Clinical endpoint ,cytokine ,EB Dosing ,medicine.diagnostic_test ,EB dosing ,Antibodies, Monoclonal ,drug ,Induction Chemotherapy ,Middle Aged ,Ulcerative colitis ,inhibitor ,030211 gastroenterology & hepatology ,Female ,Drug ,Gastrointestinal Hemorrhage ,Adult ,medicine.medical_specialty ,Inhibitor ,Injections, Subcutaneous ,Placebo ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Double-Blind Method ,Gastrointestinal Agents ,Internal medicine ,medicine ,Humans ,Dosing ,Cytokine ,Hepatology ,Dose-Response Relationship, Drug ,business.industry ,Rectum ,medicine.disease ,Endoscopy ,030104 developmental biology ,Interleukin-23 Subunit p19 ,Mayo score ,Colitis, Ulcerative ,business - Abstract
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. ispartof: GASTROENTEROLOGY vol:158 issue:3 pages:537-+ ispartof: location:United States status: published
- Published
- 2020