Dupilumab Improves Lung Function in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Inflammation: A Pooled Analysis from the Phase 3 NOTUS and BOREAS Trials

Abstract RATIONALE: There is evidence of type 2 inflammation in a subset of patients with COPD. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. In BOREAS (NCT03930732) and NOTUS (NCT04456673), patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (≥300 cells/µL blood eosinophils at screening) on background triple therapy, who received dupilumab 300 mg every 2 weeks or placebo for 52 weeks, had a statistically significant reduction in exacerbations and improved lung function. Safety was consistent with the known dupilumab safety profile. This analysis examined multiple lung function parameters in the pooled population and current and former smokers from both trials. METHODS: Change in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1), post-bronchodilator FEV1/forced vital capacity (FVC) ratio, and post-bronchodilator forced expiratory flow 25-75% of vital capacity (FEF25-75%) over time were analyzed. RESULTS: In the intention-to-treat (ITT) population, patients received dupilumab (n = 938) or placebo (n = 936); 830 patients from each group had the opportunity to reach Week 52. The ITT population was used for subgroup (current and former smokers) analysis. In the pooled ITT population who had the opportunity to reach Week 52, the baseline mean (standard deviation) pre-bronchodilator FEV1 was 1.32 (0.47) and 1.35 (0.48) L; post-bronchodilator FEV1 was 1.41 (0.47) and 1.44 (0.49) L; post-bronchodilator FEV1/FVC ratio was 0.49 (0.12) and 0.49 (0.12); and post-bronchodilator FEF25-75% was 0.56 (0.33) and 0.56 (0.33) L/s for dupilumab and placebo, respectively. By Week 12, dupilumab vs placebo improved pre-bronchodilator FEV1 (least squares [LS] mean difference [95% CI] 83 [51, 114] mL), post-bronchodilator FEV1 (LS mean difference [95% CI] 72 [40, 105] mL), post-bronchodilator FEV1/FVC (LS mean difference [95% CI] 16 [9, 23]), and post-bronchodilator FEF25-75% (LS mean difference [95% CI] 80 [44, 116] mL/s). Improvements were sustained up to Week 52. In the ITT population, the LS mean difference (95% CI) vs placebo in pre-bronchodilator FEV1 at Week 12 was 89 (52, 127) in former smokers (n = 661 dupilumab; n = 654 placebo)and 64 (20, 109) mL in current smokers (n = 275 dupilumab; n = 282 placebo). CONCLUSIONS: In 2 pivotal phase 3 trials in patients with COPD and type 2 inflammation, dupilumab improved lung function by Week 12 and sustained the improvement throughout the study period.