Dupilumab Efficacy on Exacerbations and Lung Function by Cough and Sputum Score: Pooled Results from Phase 3 BOREAS and NOTUS

Background Chronic cough and sputum production are prevalent in chronic obstructive pulmonary disease (COPD) and risk factors for exacerbations and mortality. Dupilumab, a human monoclonal antibody, blocks interleukin (IL)-4 and IL-13 signaling, key and central drivers of type 2 inflammation. This post hoc analysis of phase 3 BOREAS ( NCT03930732 ) and NOTUS ( NCT04456673 ) studies evaluated dupilumab efficacy by baseline cough and sputum scores. Methods Patients with moderate-to-severe COPD, type 2 inflammation (screening blood eosinophils ≥300 cells·µL −1 ), and patient-reported history of chronic bronchitis/cough in the year prior, on triple therapy received dupilumab 300 mg or placebo every 2 weeks for 52 weeks. Baseline cough and sputum scores were determined using Respiratory Symptoms in COPD (E-RS:COPD) questionnaire and patients were stratified by median score (3.4). Endpoints included annualized moderate or severe exacerbation rates and change from baseline in pre-bronchodilator forced expiratory volume in one second (FEV 1 ) at Week 12. Results Dupilumab versus placebo reduced exacerbations by 29% (relative risk [95% CI]: 0.71 [0.59, 0.87]) and 33% (0.67 [0.54, 0.83]) in patients with baseline cough and sputum scores of ≥3.4 and <3.4, respectively (interaction p-value=0.7080). At Week 12, dupilumab versus placebo improved FEV 1 in patients with baseline scores of ≥3.4 (least squares mean difference: 0.091 [95% CI: 0.051, 0.131]) and in those with <3.4 (0.081 [0.036, 0.125]; interaction p-value=0.7463). Conclusion In this post hoc analysis, dupilumab reduced exacerbations and improved lung function in patients with COPD and type 2 inflammation regardless of baseline E-RS:COPD cough and sputum scores.