This is Jeffrey Drazen for the New England Journal of Medicine. Asthma associated with a type 2 immune response is characterized by increased numbers of type 2 helper T cells in the airway, mast cell activation, eosinophilic airway infiltration, and the release of pro-inflammatory cytokine, including interleukins 4, 5 and 13. Dupilumab is a monoclonal antibody that blocks
cytokine signaling by interleukins 4 and 13; it has the potential to decrease type 2 immune
responses. This randomized, double-blind, placebo-controlled, parallel-group trial assessed the efficacy of dupilumab in just over 1900 patients with moderate to severe asthma, that was refractory to maximized standard-of-care controller therapy. Patients were randomized to receive 200 or 300 mg of dupilumab or placebo by subcutaneous-injection every 2 weeks for 52 weeks in addition to the usual treatment. The primary outcome was the annualized rate of severe exacerbations. At 52 weeks, the exacerbation rate was 0.46 in patients who received 200 mg of dupilumab, and 0.87 in patients who received placebo. Similar results were seen with the higher
dose of dupilumab. The absolute change from baseline to week 12 in the Prebronchodilator
Forced Expiratory Volume in 1 second, the FEV1, was also assessed. At 12 weeks, the mean change in FEV1 in patients randomized to dupilumab was significantly greater than change with placebo. In addition to injection-site reactions, which were more common in the dupilumab group, just over 4% of patients receiving dupilumab versus 0.6% with placebo developed transient blood eosinophilia. The authors conclude that dupilumab provided a significant reduction in the rate of severe exacerbations and improved lung function in patients with previously uncontrolled moderate to severe asthma. Full trial results are available at NEJM.org.