Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial
| Autor: | Oliver N. Keene, Hector Ortega, Ian D. Pavord, Eugene R. Bleecker, Pascal Chanez, Roland Buhl, Stephanie Korn, Peter H. Howarth |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Placebo-controlled study Fevipiprant Antibodies Monoclonal Humanized Placebo Lebrikizumab Drug Administration Schedule Leukocyte Count Young Adult chemistry.chemical_compound Double-Blind Method Reslizumab Internal medicine Secondary Prevention medicine Humans Anti-Asthmatic Agents Pulmonary Eosinophilia Child Glucocorticoids Aged Asthma Dose-Response Relationship Drug business.industry General Medicine Middle Aged medicine.disease Benralizumab Eosinophils Treatment Outcome chemistry Physical therapy Drug Therapy Combination Female Interleukin-5 business Mepolizumab medicine.drug |
| Zdroj: | The Lancet. 380:651-659 |
| ISSN: | 0140-6736 |
| Popis: | BACKGROUND: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. METHODS: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506. FINDINGS: 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p |
| Databáze: | OpenAIRE |
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