Mepolizumab for severe eosinophilic asthma (DREAM): A multicentre, double-blind, placebo-controlled trial

Background Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway infl ammation. Early studies suggest that inhibition of eosinophilic airway infl ammation with mepolizumab- a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish effi cacy, 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 infl ammation. 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 09% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratifi ed by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically signifi cant asthma exacerbations, which were defi ned 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 signifi cant. The rate of clinically signifi cant exacerbations was 240 per patient per year in the placebo group, 124 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<00001), 146 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=00005), and 115 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<00001). Three patients died during the study, but the deaths were not deemed to be related to treatment. Interpretation Mepolizumab is an eff ective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. Funding GlaxoSmithKline.