Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial
| Autor: | Erika H. De Boever, Adrian P. Serone, Anthony Cahn, Sally E. Wenzel, Sivayogan S. Thiagarajah, Isabelle Pouliquen, Phil Overend, Nicholas Locantore, Mair M. Jenkins, Claire Ashman, Inderpal S. Panesar, Tracey J. Wright |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male medicine.medical_specialty Immunology Placebo Severity of Illness Index Fluticasone propionate law.invention Lethargy Randomized controlled trial law Internal medicine Clinical endpoint medicine Immunology and Allergy Humans Anti-Asthmatic Agents Adverse effect Asthma Interleukin-13 business.industry Antibodies Monoclonal Middle Aged medicine.disease Treatment Outcome Asthma Control Questionnaire Anesthesia Female business medicine.drug |
| Zdroj: | The Journal of allergy and clinical immunology. 133(4) |
| ISSN: | 1097-6825 |
| Popis: | 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 FEV 1 (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. |
| Databáze: | OpenAIRE |
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