In a phase 3 trial, dupilumab therapy improved outcomes in patients with COPD who had type 2 inflammation as indicated by elevated blood eosinophil counts. Compared with placebo, patients had fewer exacerbations, better lung function and quality of life, and less severe respiratory symptoms when given the fully human monoclonal antibody, which blocks the key drivers of type 2 inflammation (the shared receptor component for interleukin-4 and interleukin-13).
Participants had COPD with a blood eosinophil count of 300 per µL and an elevated exacerbation risk despite the use of standard triple therapy. They were randomized to double-blinded dupilumab 300 mg or placebo subcutaneously once every 2 weeks for 52 weeks.
Based on a primary endpoint of the annualized rate of moderate or severe exacerbations of COPD, the study found: “A total of 939 patients underwent randomization: 468 to the dupilumab group and 471 to the placebo group. The annualized rate of moderate or severe exacerbations was 0.78 (95% confidence interval [CI], 0.64 to 0.93) with dupilumab and 1.10 (95% CI, 0.93 to 1.30) with placebo (rate ratio, 0.70; 95% CI, 0.58 to 0.86; P<0.001). The prebronchodilator FEV1 increased from baseline to week 12 by a least-squares (LS) mean of 160 ml (95% CI, 126 to 195) with dupilumab and 77 ml (95% CI, 42 to 112) with placebo (LS mean difference, 83 ml; 95% CI, 42 to 125; P<0.001), a difference that was sustained through week 52. At week 52, the [St. George’s Respiratory Questionnaire] score had improved by an LS mean of −9.7 (95% CI, −11.3 to −8.1) with dupilumab and −6.4 (95% CI, −8.0 to −4.8) with placebo (LS mean difference, −3.4; 95% CI, −5.5 to −1.3; P=0.002). The [Evaluating Respiratory Symptoms in COPD] score at week 52 had improved by an LS mean of −2.7 (95% CI, −3.2 to −2.2) with dupilumab and −1.6 (95% CI, −2.1 to −1.1) with placebo (LS mean difference, −1.1; 95% CI, −1.8 to −0.4; P=0.001). The numbers of patients with adverse events that led to discontinuation of dupilumab or placebo, serious adverse events, and adverse events that led to death were balanced in the two groups.”
Editorial: “It is noteworthy that the mean age of the patients in the BOREAS trial was 65 years,” an editorialist writes. “It is now well established that there are various lung-function trajectories through life that can lead to COPD in adulthood and that early life events that limit lung growth and development are critical factors determining respiratory health later in life. It is possible, therefore, that the diagnosis and treatment of COPD at a younger age may yield better results. The recently released Global Initiative for Chronic Obstructive Lung Disease (GOLD) report clearly emphasizes the need to study COPD in young patients.