TOPLINE:

Dupilumab reduced mucus plugging and volume in patients with moderate-to-severe type 2 asthma within 4 weeks of starting treatment, improving both global and distal lung function. These improvements were more pronounced in patients who had a higher number of mucus plugs in airways.

METHODOLOGY:

• Researchers conducted a post hoc analysis of the VESTIGE study to examine the effect of dupilumab on mucus plugging and mucus volume in patients with moderate-to-severe type 2 asthma.
• Overall, 109 adult patients (18-70 years of age) who received stable treatment with medium- or high-dose inhaled corticosteroids (ICS) with a second or third controller were randomly assigned to receive add-on subcutaneous dupilumab 300 mg (n = 72) or volume-matched placebo (n = 37) every 2 weeks for 24 weeks.
• Mucus plug score quantifies the number of mucus plugs in the airways and were derived from high-resolution CT scans obtained at weeks 0, 4, and 24, using a validated system; scores ranged from 0 to 20 in 0.5-point increments, with 4-20 classified as high scores and 0-3.5 as low scores.
• Efficacy endpoints were the proportion of patients with mucus plug score categories 0, 0.5-3.5, and 4-20 at baseline and weeks 4 and 24 and the change in global lung mucus plug score and volume from baseline to weeks 4 and 24.
• Other efficacy endpoints included the proportion of fractional exhaled nitric oxide (FeNO) responders and changes from baseline in pre- or postbronchodilator forced expiratory volume in 1 second (FEV₁).

TAKEAWAY:

• Dupilumab treatment reduced the proportion of patients with high mucus plug scores from 67.2% at baseline to 32.8% by week 24, whereas the placebo group maintained similar proportions (73.3% at baseline to 76.7% by week 24).
• At week 24, dupilumab significantly reduced global lung mucus plug scores in patients who had received either medium- or high-dose ICS compared with placebo at baseline (P < .001 for both). It also significantly reduced global lung mucus volume in patients on high‑dose (P < .005) or medium‑dose (P < .001) ICS at baseline.
• A significantly higher proportion of patients receiving dupilumab than placebo achieved FeNO < 25 ppb at week 24 in both high (odds ratio [OR], 6.64; P = .003) and low (OR, 8.54; P = .024) baseline mucus plug score subgroups.
• In patients with high mucus plug scores at baseline, dupilumab significantly increased both pre-bronchodilator (P = .0002) and post-bronchodilator (P = .0059) FEV₁ from baseline compared with placebo.

IN PRACTICE:

“By providing a standardized framework for assessing mucus pathology, the mucus plug score complements other exploratory measures, such as mucus volume, in elucidating the role of mucus in airway obstruction,” the authors of the study wrote.

SOURCE:

The study was led by Celeste Porsbjerg, MD, PhD, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. It was published online on October 27, 2025, in the American Journal of Respiratory and Critical Care Medicine.

LIMITATIONS:

The VESTIGE study was not powered to detect statistically significant differences within patient subgroups stratified by baseline mucus plug score. Limited demographic and clinical diversity across subgroups may have restricted the generalizability of the findings. Colocalization analyses linking resolved mucus plugs with specific areas of lung function recovery were not performed.

DISCLOSURES:

The study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Several authors reported receiving grants; speaker and lecture fees; royalties; research, nonfinancial, and travel support; and honoraria for presentations outside speakers bureaus and serving as consultants or advisory board members for various pharmaceutical companies. Five authors reported being employees of the sponsor companies, of whom four reported holding stock and/or stock options and three reported having shareholdings in the sponsor companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.