Effect of Dupilumab on Mucus Burden in Patients with Moderate-to-Severe Asthma: The VESTIGE Trial.

Porsbjerg, Celeste; Dunican, Eleanor M; Lugogo, Njira L; Castro, Mario; Papi, Alberto; Backer, Vibeke; Brightling, Christopher E; Bourdin, Arnaud et al. · Am J Respir Crit Care Med · 2025

rct · Level II

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Abstract

Chronic mucus hypersecretion contributes to airway obstruction in asthma. Assess dupilumab efficacy by baseline mucus plug score. 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 (<i>n</i>=72) or placebo (<i>n</i>=37) every 2 weeks for 24 weeks. <i>Post hoc</i> analyses included mucus plug score change from baseline, and patient proportion achieving FeNO <25 ppb, percent predicted FEV<sub>1</sub>, 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). 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; <i>P</i> = 0.003/8.54; <i>P</i> = 0.024). Dupilumab versus placebo significantly increased pre-/post-bronchodilator percent predicted FEV<sub>1</sub> (least squares mean difference (LSMD) [95% CI]: 16.77 percentage points [9.81-23.73]; <i>P</i> <0.0001/12.70 [3.87-21.52]; <i>P</i> = 0.0055) and pre-bronchodilator FVC (LSMD [95% CI]: 0.42 mL [0.17-0.66]; <i>P</i> = 0.001), and numerically improved post-bronchodilator FVC (LSMD [95% CI]: 0.30 mL [0.01-0.59]; <i>P</i> = 0.0399) in the high-mucus-plug score subgroup. 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. gov, ID: NCT04400318.