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Introduction and Objectives Type 2 inflammation (indicated by elevated blood eosinophil counts [BEC]) in patients with chronic obstructive pulmonary disease (COPD) often correlates with higher exacerbation risk. In BOREAS and NOTUS, dupilumab significantly reduced exacerbation rates and improved lung function. Safety was consistent with the known dupilumab safety profile. This post hoc analysis evaluated dupilumab efficacy in patients, grouped by baseline BEC ≥150 cells/µL or ≥300 cells/µL.Methods BOREAS ( NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, placebo-controlled trials, enrolled 1,874 patients (40–85 years) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening BEC ≥300 cells/µL). Patients were randomized to dupilumab 300 mg or placebo q2w for 52 weeks. Baseline BEC for subgroups was measured at randomization. This analysis included patients from the intention-to-treat population, grouped by baseline BEC ≥150 cells/µL, or ≥300 cells/µL. Endpoints assessed included annualized moderate or severe exacerbation rate, change from baseline to Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ), and Evaluating Respiratory Symptoms (E-RS): COPD total scores. Data are shown as least squares mean difference vs placebo (95% CI) at Week 52, unless stated otherwise.Results Of 1,874 patients, 1,703 (dupilumab n=855; placebo n=848) had baseline BEC ≥150 cells/µL, and 1,135 (dupilumab n=573; placebo n=562) had baseline BEC ≥300 cells/µL. Dupilumab reduced annualized exacerbation rates vs placebo by 36.9% (BEC ≥150 cells/µL) and 35.8% (BEC ≥300 cells/µL). Dupilumab improved pre-bronchodilator FEV 1 by 76 mL (42, 110; BEC ≥150 cells/µL) and 92 mL (51, 133; BEC ≥300 cells/µL) and reduced patient-reported SGRQ scores at Week 52 by −3.1 points (−4.7, −1.4; BEC ≥150 cells/µL) and −4.0 points (−6.0, −1.9; BEC ≥300 cells/µL), as well as ERS:COPD scores by −1.0 point (−1.5, −0.4; BEC ≥150 cells/µL) and −1.0 point (−1.7, −0.4;BEC ≥300 cells/µL).Conclusions In patients with COPD and type 2 inflammation, dupilumab reduced annualized exacerbation rates and symptom burden, and improved lung function and quality of life, with greater treatment effects observed in those patients with higher baseline BEC.