Efficacy and safety of mepolizumab in hypereosinophilic syndrome: A phase III, randomized, placebo-controlled trial.

Autor: Roufosse F; Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: froufoss@ulb.ac.be., Kahn JE; Department of Internal Medicine, Hôpital Ambroise Paré, Université Versailles-Saint Quentin-en-Yvelines, Boulogne-Billancourt, France., Rothenberg ME; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio., Wardlaw AJ; Institute for Lung Health, University of Leicester, Leicester, United Kingdom., Klion AD; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md., Kirby SY; Respiratory Therapeutic Area, GSK, Research Triangle Park, NC., Gilson MJ; Respiratory Research and Development, GSK, Uxbridge, Middlesex, United Kingdom., Bentley JH; Clinical Statistics, GSK, Uxbridge, Middlesex, United Kingdom., Bradford ES; Respiratory Therapeutic Area, GSK, Research Triangle Park, NC., Yancey SW; Respiratory Therapeutic Area, GSK, Research Triangle Park, NC., Steinfeld J; Respiratory Research & Development, GSK, Collegeville, Pa., Gleich GJ; Department of Dermatology, School of Medicine, University of Utah, Salt Lake City, Utah.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2020 Dec; Vol. 146 (6), pp. 1397-1405. Date of Electronic Publication: 2020 Sep 18.
DOI: 10.1016/j.jaci.2020.08.037
Abstrakt: Background: Anti-IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear.
Objective: We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES.
Methods: This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed.
Results: The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P = .002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P = .003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]).
Conclusions: Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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