Effect of dupilumab on mucus burden in patients with moderate-to-severe asthma: the VESTIGE trial

Rationale: Chronic mucus hypersecretion contributes to airway obstruction in asthma. Objectives: To assess dupilumab efficacy by baseline mucus plug score. Methods: In VESTIGE (NCT04400318), adults with moderate-to-severe asthma, baseline blood eosinophils ≥300 cells/μL, and fractional exhaled nitric oxide (FeNO) ≥25 ppb received dupilumab 300 mg (n = 72) or placebo (n = 37) every 2 weeks for 24 weeks. Post hoc analyses included mucus plug score change from baseline, and patient proportion achieving FeNO <25 ppb, percent predicted FEV1, and FVC stratified by baseline mucus plug score (high/low defined by score ≥4 or 0-3.5, respectively, derived from high-resolution computed tomography scans). Measurements and main results: Fewer dupilumab-receiving patients had high mucus plug score at week 24 than at baseline (32.8% vs 67.2%); proportions remained similar in placebo-receiving patients (76.7% vs 73.3%). Dupilumab versus placebo recipients were more likely to achieve FeNO <25 ppb in high-/low-mucus-plug score subgroups (odds ratio, 6.64; P = .003/8.54; P = .024). Dupilumab versus placebo significantly increased pre-/post-bronchodilator percent predicted FEV1 (least squares mean difference [LSMD], 16.77 percentage points [95% CI, 9.81-23.73]; P <.0001 [pre] and 12.70 [95% CI, 3.87-21.52]; P = .0055 [post]) and pre-bronchodilator FVC (LSMD, 0.42 mL [95% CI, 0.17-0.66]; P = .001), and numerically improved post-bronchodilator FVC (LSMD, 0.30 mL [95% CI, 0.01-0.59]; P = .0399) in the high-mucus-plug score subgroup. Conclusions: Dupilumab reduced mucus plug scores and improved lung function in patients with moderate-to-severe asthma with high baseline mucus plug score, and increased the likelihood of achieving FeNO <25 ppb regardless of baseline mucus plug score.