Abstract
RATIONALE: Chronic mucus hypersecretion contributes to airway obstruction in asthma. OBJECTIVES: 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 FEV(1), and FVC stratified by baseline mucus plug score (high/low defined by score ≥4/0-3.5, 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 = 0.003/8.54; P = 0.024). Dupilumab versus placebo significantly increased pre-/post-bronchodilator percent predicted FEV(1) (least squares mean difference (LSMD) [95% CI]: 16.77 percentage points [9.81-23.73]; P <0.0001/12.70 [3.87-21.52]; P = 0.0055) and pre-bronchodilator FVC (LSMD [95% CI]: 0.42 mL [0.17-0.66]; P = 0.001), and numerically improved post-bronchodilator FVC (LSMD [95% CI]: 0.30 mL [0.01-0.59]; P = 0.0399) 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. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT04400318.