Dupilumab reduces exacerbations and improves lung function in patients with chronic obstructive pulmonary disease and emphysema: Phase 3 randomized trial (BOREAS)

Abstract

Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation in the phase 3 BOREAS trial.

Objective: To assess clinical outcomes in patients from BOREAS by emphysema status.

Methods: Patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/μL) on maximal inhaled therapy were randomized to add-on dupilumab 300 mg or placebo every 2 weeks for 52 weeks. We assessed the annualized moderate/severe COPD exacerbation rates over 52 weeks and change from baseline to Week 12 in prebronchodilator forced expiratory volume in 1 s (FEV₁) in patients with and without investigator-reported emphysema.

Results: Investigator-reported emphysema was present in 306/939 patients (32.6 %) at baseline. Dupilumab reduced exacerbation rates vs placebo by 29 % (relative risk [RR] 0.71 [95 % CI 0.53-0.95]) and 31 % (RR 0.69 [95 % CI 0.53-0.89]) in patients with and without emphysema, respectively. Prebronchodilator FEV₁ least squares mean difference from baseline to Week 12 for dupilumab vs placebo was 0.07 L ([95 % CI 0.002-0.14]) and 0.09 L ([95 % CI 0.04-0.14]) in patients with and without emphysema, respectively. No treatment by emphysema interaction effect was observed for the annualized rate of exacerbations (P value for interaction = 0.8296) or change in prebronchodilator FEV₁ (P value for interaction = 0.6438).

Conclusion: Dupilumab efficacy was similar in patients with COPD and type 2 inflammation, with or without investigator-reported emphysema.

Keywords: BMI body mass index; COPD; Dupilumab; Emphysema; Eosinophils; Exacerbations; Type 2 inflammation.