ArticlesMepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial
Introduction
Severe asthma is associated with substantial morbidity, mortality, and health-care costs.1 Recurrent asthma exacerbations are a major problem in some patients and can predominate in a subgroup with eosinophilic airway inflammation.2 Mepolizumab—a humanised monoclonal antibody against interleukin 5—selectively and effectively inhibits eosinophilic airway inflammation.3, 4, 5, 6 Two small proof-of-concept studies7, 8 showed that treatment with this drug reduced the risk of asthma exacerbations. A larger study with a diverse population is thus needed to establish the best possible dose, efficacy, safety, and patient characteristics associated with the response to mepolizumab treatment.
In the Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) trial, we tested the hypothesis that mepolizumab reduces the frequency of asthma exacerbations. Our secondary aims were to assess the effects of treatment on blood and sputum eosinophil counts, asthma control, asthma-related quality of life, and forced expiratory volume in 1 s (FEV1).
Section snippets
Study design and participants
We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries (Argentina, Australia, Canada, Chile, France, Germany, South Korea, Poland, Romania, Russia, Ukraine, the UK, and the USA) between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12–74 years and had a clinical diagnosis of asthma supported by one or more other characteristics: variability in diurnal peak expiratory flow (PEF) of more than 20% for at least 3 days during the 2-week run-in
Results
Figure 1 shows the trial profile. Of the 616 patients who received treatment and constituted the intention-to-treat population, 520 (84%) completed treatment. Table 1 shows baseline characteristics.
806 exacerbations requiring use of oral corticosteroids, admission, or a visit to an emergency department were reported. Of those, 776 (96%) were supported by objective assessments that asthma had worsened and were deemed clinically significant. 30 (4%; eight in the placebo group, 12 in the 75 mg
Discussion
We have shown that mepolizumab significantly reduces the number of asthma exacerbations in patients with severe eosinophilic asthma compared with placebo. Additionally, treatment lowers blood and sputum eosinophil counts and was well tolerated for 12 months. The DREAM study is the largest trial undertaken in severe asthma as yet (panel). The reported effects are clinically important and suggest that neutralising interleukin 5 addresses a major unmet medical need in a population with substantial
References (28)
- et al.
Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response
Lancet
(2000) - et al.
Measurement properties and interpretation of three shortened versions of the asthma control questionnaire
Respir Med
(2005) - et al.
Severe asthma in adults: what are the important questions?
J Allergy Clin Immunol
(2007) - et al.
Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial
Lancet
(2002) - et al.
Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial
Lancet
(2011) Global strategy for asthma management and prevention
- et al.
Cluster analysis and clinical asthma phenotypes
Am J Respir Crit Care Med
(2008) - et al.
Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics
J Clin Invest
(2003) - et al.
A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma
Am J Respir Crit Care Med
(2007) - et al.
Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway
Am J Respir Crit Care Med
(2003)
Mepolizumab and exacerbations of refractory eosinophilic asthma
N Engl J Med
Mepolizumab for prednisone-dependent asthma with sputum eosinophilia
N Engl J Med
Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions
Am J Respir Crit Care Med
Development and validation of a questionnaire to measure asthma control
Eur Respir J
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