Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial.

Autor: De Boever EH; Alternative Discovery and Development, GlaxoSmithKline, King of Prussia, Pa. Electronic address: erika.h.deboever@gsk.com., Ashman C; Biopharm Research, GlaxoSmithKline, Stevenage, United Kingdom., Cahn AP; Respiratory Discovery Medicine, GlaxoSmithKline, Stevenage, United Kingdom., Locantore NW; Respiratory Medicines Development, GlaxoSmithKline, Research Triangle Park, NC., Overend P; II/Biopharm Clinical Statistics, GlaxoSmithKline, Stevenage, United Kingdom., Pouliquen IJ; Clinical Pharmacology Modeling and Simulation, GlaxoSmithKline, Middlesex, United Kingdom., Serone AP; Genentech, Research and Early Development, San Francisco, Calif., Wright TJ; Biopharm Research, GlaxoSmithKline, Stevenage, United Kingdom., Jenkins MM; Emerging Markets R&D, GlaxoSmithKline, Brentford, United Kingdom., Panesar IS; ISP Pharma, Birmingham, United Kingdom., Thiagarajah SS; Global Medical Safety, Janssen Pharmaceuticals, High Wycombe, United Kingdom., Wenzel SE; Asthma Institute, University of Pittsburgh Medical Center, Pittsburgh, Pa.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2014 Apr; Vol. 133 (4), pp. 989-96. Date of Electronic Publication: 2014 Feb 28.
DOI: 10.1016/j.jaci.2014.01.002
Abstrakt: Background: Approximately 5% to 10% of asthmatic patients achieve incomplete symptom control on current therapies. The association of IL-13 with asthma pathology and reduced corticosteroid sensitivity suggests a potential benefit of anti-IL-13 therapy in refractory asthma. GSK679586, a humanized mAb, inhibits IL-13 binding to both IL-13 receptor α1 and α2.
Objectives: We sought to evaluate the efficacy and safety of GSK679586 in patients with severe asthma refractory to maximally indicated doses of inhaled corticosteroids.
Methods: Patients who remained symptomatic (Asthma Control Questionnaire score ≥1.5) after uptitration to 1000 μg/d fluticasone propionate or greater were randomized to 3 once-monthly intravenous infusions of 10 mg/kg GSK679586 (n = 99) or placebo (n = 99).
Results: Treatment differences in adjusted mean change from baseline over 12 weeks were nonsignificant for Asthma Control Questionnaire symptom scores (the primary end point; GSK679586 = -0.31, placebo = -0.17, P = .058) and FEV₁ (GSK679586 = -0.01, placebo = 0.03, P = .276). Similar analyses in patients with increased serum IgE levels, blood eosinophil counts, or both were also negative. Incidence of asthma exacerbations was similar between treatments. Most adverse events were nonserious and unrelated to treatment. Two GSK679586-treated patients had treatment-related serious adverse events (lethargy and supraventricular extrasystoles).
Conclusions: Although well tolerated, GSK679586 did not demonstrate clinically meaningful improvements in asthma control, pulmonary function, or exacerbations in patients with severe asthma. Further studies are needed to determine whether therapies targeting IL-13, the functionally related IL-4 cytokine, or both can provide clinical benefit in patients with severe refractory asthma or a subpopulation of these patients beyond that achievable with high-dose corticosteroids.
(Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
Databáze: MEDLINE
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