Mepolizumab for Severe Eosinophilic Asthma (DREAM): A Multicentre, Double-Blind, Placebo-Controlled Trial

Lancet. 2012 Aug 18;380(9842):651-9. doi: 10.1016/S0140-6736(12)60988-X.

Abstract

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<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment.

Interpretation: Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma.

Funding: GlaxoSmithKline.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Asthmatic Agents / administration & dosage
  • Anti-Asthmatic Agents / adverse effects
  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Asthma / blood
  • Asthma / complications
  • Asthma / prevention & control*
  • Child
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Eosinophils / pathology
  • Female
  • Glucocorticoids / administration & dosage
  • Humans
  • Interleukin-5 / antagonists & inhibitors
  • Leukocyte Count
  • Male
  • Middle Aged
  • Pulmonary Eosinophilia / blood
  • Pulmonary Eosinophilia / etiology
  • Pulmonary Eosinophilia / prevention & control*
  • Secondary Prevention
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • Interleukin-5
  • mepolizumab

Associated data

  • ClinicalTrials.gov/NCT01000506