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

Autor: Amy D. Klion, Florence Roufosse, Marc E. Rothenberg, Suyong Yun Kirby, Jane H Bentley, Jonathan Steinfeld, Martyn J. Gilson, Eric S. Bradford, Steven W. Yancey, Andrew J. Wardlaw, Jean-Emmanuel Kahn, Gerald J. Gleich
Přispěvatelé: Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], GlaxoSmithKline, GSK: NCT02836496, 200622 GlaxoSmithKline Australia, GSK AstraZeneca GlaxoSmithKline Australia, GSK, This study was funded by GlaxoSmithKline (GSK study ID: 200622, NCT02836496 ). Editorial support (in the form of writing assistance, including development of the initial draft based on author direction, assembling tables and figures, collating authors’ comments, grammatical editing, and referencing) was provided by Laura Gardner, PhD, of Fishawack Indicia Ltd, UK, and was funded by GSK ., Disclosure of potential conflict of interest: F. Roufosse reports consultancy fees from AstraZeneca, GlaxoSmithKline (GSK), and Knopp Biosciences. J.-E. Kahn reports consulting fees for advisory boards from AstraZeneca and GSK, research funding from AstraZeneca and GSK, and participation in clinical trials sponsored by AstraZeneca. M. E. Rothenberg is a consultant for Allakos, Arena Pharmaceuticals, AstraZeneca, Serpin Pharma, and Celgene, owns stocks/shares in ClostrBio, PulmOne Advanced Medical Devices, Serpin Pharma, and Spoon Guru, has received royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate, and is an inventor of patents owned by Cincinnati Children’s Hospital Medical Center. A. J. Wardlaw reports fees for participation in advisory boards from GSK, and participation in clinical trials sponsored by AstraZeneca, GSK, and Pulmocide. A. D. Klion reports funding to cover time reviewing the trial protocol and results from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. S. Y. Kirby was an employee of GSK when this research was conducted and holds stocks/shares in GSK. E. S. Bradford is a former employee of GSK and is currently employed by Aeglea BioTherapeutics, Austin, Texas, and has stocks/shares in both companies. M. J. Gilson, J. H. Bentley, S. W. Yancey, and J. Steinfeld are all employees of GSK and own stocks/shares. G. J. Gleich is currently an employee of NexEos Diagnostics, has acted as a consultant for Genentech, GSK, and Knopp Biosciences, has received royalties from the Mayo Foundation, and has a royalty sharing agreement with Teva.
Rok vydání: 2020
Předmět:
Zdroj: Journal of Allergy and Clinical Immunology
Journal of Allergy and Clinical Immunology, Elsevier, 2020, 146 (6), pp.1397-1405. ⟨10.1016/j.jaci.2020.08.037⟩
Journal of allergy and clinical immunology
ISSN: 0091-6749
Popis: 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.
SCOPUS: ar.j
info:eu-repo/semantics/published
Databáze: OpenAIRE
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