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

Abstract 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.