Dupilumab Efficacy in Patients With Chronic Obstructive Pulmonary Disease (COPD) With Type 2 Inflammation Across Baseline Eosinophil Counts

Abstract RATIONALE: Type 2 (T2) inflammation in patients with chronic obstructive pulmonary disease (COPD) is evidenced by elevated blood eosinophil counts (BEC), often correlating with higher risk for exacerbations. In the BOREAS and NOTUS trials, add-on dupilumab 300 mg every 2 weeks (q2w) vs placebo significantly reduced exacerbation rates and improved lung function in patients with COPD and T2 inflammation. This post-hoc analysis of pooled data from BOREAS and NOTUS evaluated efficacy of dupilumab in patients stratified by baseline BEC of ≥150 cells/µL or ≥300 cells/µL. METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), both phase 3, randomized, placebo-controlled trials, enrolled 1,874 patients (40-85 years) with COPD, moderate-to-severe airflow limitation, and T2 inflammation. The inclusion criterion was screening BEC ≥300 cells/µL (at Visit 1, 1-4 weeks before randomization). Baseline BEC was measured at day of randomization. Patients were randomized to dupilumab 300 mg or placebo q2w for 52 weeks. This analysis included patients from the intention-to-treat (ITT) population of BOREAS and NOTUS, stratified by baseline BEC ≥150 cells/µL, 150-300 cells/µL or ≥300 cells/µL (at randomization). Endpoints assessed included annualized moderate-to-severe exacerbation rate, change from baseline to Week 52 in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1) and St. George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Of 1,873 patients, 1,703 (dupilumab n = 855; placebo n = 848) had baseline BEC ≥150 cells/µL, and 1,135 (dupilumab n = 573; placebo n = 562) still had baseline BEC ≥300 cells/µL. Dupilumab vs placebo reduced annualized exacerbation rates by up to 36.9%. At Week 52, dupilumab vs placebo improved pre-bronchodilator FEV1 by (least squares [LS] mean difference [95% CI]) 0.07 (0.04, 0.11) L in the ITT population, 0.08 (0.04, 0.11) L in patients with baseline BEC ≥150 cells/µL, and 0.09 (0.05, 0.13) L in those with baseline BEC ≥300 cells/µL. Similar results were observed for changes in post-bronchodilator FEV1. Dupilumab also reduced SGRQ total scores at Week 52 by (LS mean [95% CI]) −3.37 (−4.95, −1.78) (ITT population), −3.07 (−4.7, −1.44) (baseline BEC ≥150 cells/µL), and −3.98 (−6.01, −1.95) (baseline BEC ≥300 cells/µL). Overall study safety of BOREAS and NOTUS was consistent with known dupilumab profile. CONCLUSIONS: In patients with COPD and T2 inflammation, dupilumab reduced annualized exacerbation rates, and improved lung function and quality of life in patients in ITT and across baseline BEC of ≥150 cells/µL and ≥300 cells/µL, with slightly greater treatment effects observed in patient with higher baseline BEC.