Abstract Rationale Despite receiving optimal inhaled therapy, many patients with chronic obstructive pulmonary disease (COPD) have persistent cough and sputum. In BOREAS and NOTUS, dupilumab significantly reduced exacerbations and improved lung function in patients with COPD and type 2 inflammation. This post hoc analysis examined the impact of dupilumab on cough outcomes in patients with frequent (productive) cough and explored factors linked to improvement. Methods Phase 3, randomized, placebo-controlled trials BOREAS (NCT03930732) and NOTUS (NCT04456673) enrolled patients (40-85 years) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on inhaled triple therapy. Patients received add-on dupilumab 300 mg or placebo q2w for 52 weeks. At baseline, patients were stratified by “frequent cough” (St. George’s Respiratory Questionnaire SGRQ score ≥3 for coughing several/most days a week in the last 3 months) or “frequent productive cough” (additional SGRQ score ≥3 for bringing up phlegm several/most days per week). Endpoints were changes from baseline to Week 52 in Evaluating Respiratory Symptoms in COPD (E-RS:COPD) cough and sputum domain scores (CSDs) by univariate and multivariable regression analysis. Results Analysis included the intent-to-treat population (dupilumab: N = 938; placebo: N = 936). At Week 52, dupilumab reduced E-RS:COPD CSDs vs placebo in those with frequent/frequent productive cough at baseline (Figure). In univariate analyses conducted for dupilumab and placebo arms separately, a decrease from baseline to Week 52 in CSDs showed statistical association with an increase in post-bronchodilator forced expiratory volume in 1 second (FEV1); regression parameter estimate (r): dupilumab: -0.75 95% CI: -1.06, -0.44, P0.0001; placebo: r=-0.41 95% CI: -0.76, -0.06, P=0.0223). Current smokers showed numerically higher CSD scores than former smokers (dupilumab: r=0.13 95% CI: -0.14, 0.39, P=0.3538; placebo: r=0.27 95% CI: 0.03, 0.51, P=0.026). Multivariable analysis was conducted for baseline CSDs adjusting for prognostic factors showed a significant association between baseline CSDs and baseline post-bronchodilator FEV1 (regression coefficient estimate: 0.84 95% CI: 0.35, 1.33, P=0.0009); current smokers had 0.37 higher CSDs than former smokers (95% CI: 0.18, 0.57, P=0.0002). Correlations of baseline values of cough with FEV1 reversibility, blood eosinophil count, neutrophil count, and FeNO showed no significance (r=0.23 [95% CI: -0.08, 0.53), P=0.1475; r=0.02 [95% CI: -0.03, 0.07), P=0.4412; r=-0.0019 [95% CI: -0.01, 0.00), P=0.3194, respectively). Conclusion Dupilumab significantly improved cough and sputum symptoms in patients with COPD and frequent productive cough. Improvements correlated with higher baseline lung function but not type 2 inflammation biomarkers. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifiers: NCT03930732 and NCT04456673
Satia et al. (Fri,) studied this question.