Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial.

Summary

Dupilumab significantly increased the proportion of patients achieving FeNO <25 ppb (57% vs 11%; OR 9.8) and reduced CT-derived mucus plugging compared with placebo. Functional respiratory imaging showed increases in specific airway volume and flow, consistent with improvements in lung function and asthma control over 24 weeks.

Key Findings

• At week 24, FeNO <25 ppb was achieved in 57% with dupilumab vs 11% with placebo (OR 9.8, p<0.001).
• CT-based mucus plugging score decreased more with dupilumab than placebo (least squares mean difference −2.62; 95% CI −3.92 to −1.31).
• Specific regional airway volume and flow increased with dupilumab, aligning with improved lung function and asthma control.

Clinical Implications

Dupilumab may benefit T2-high asthma by reducing mucus plugging and improving regional airflow; functional respiratory imaging could serve as a biomarker to phenotype patients and monitor response.

Limitations

• Modest sample size and 24-week duration limit long-term generalizability
• Imaging surrogates; not powered for exacerbation outcomes

Future Directions

Validate imaging biomarkers for treatment selection and response monitoring; evaluate long-term exacerbation and mucus-related outcomes; test generalizability across T2 phenotypes and comorbid mucus hypersecretion.