Effect of dupilumab on small airways measured by airway oscillometry in VESTIGE.

Abstract

Patients with asthma are at risk of airflow obstruction due to small-airway dysfunction (SAD), which responds poorly to current therapies. VESTIGE (NCT04400318) was a phase 4 study that evaluated the impact of dupilumab on airway inflammation using spirometry, airway oscillometry, and functional respiratory imaging. We sought to evaluate the effect of dupilumab on SAD in moderate to severe asthma. Patients with moderate to severe asthma and blood eosinophils greater than or equal to 300 cells/μL and fractional exhaled nitric oxide greater than or equal to 25 parts per billion at screening were randomized 2:1 to dupilumab 300 mg every 2 weeks or matched placebo for 24 weeks. SAD-related secondary and exploratory end points were change from baseline over time in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (FEF_25%-75%), frequency dependence of airway resistance, reactance area, airway wall area and thickness at total lung capacity, and air trapping at functional residual capacity. Of 109 patients, 72 received dupilumab and 37 received placebo. At week 24, dupilumab versus placebo nominally significantly improved prebronchodilator FEF_25%-75% (least squares mean difference [95% CI], 0.51 L/s [0.21 to 0.80]) and postbronchodilator FEF_25%-75% (0.50 L/s [0.19 to 0.80]). Dupilumab decreased frequency dependence of airway resistance and improved reactance area at week 24 versus placebo. Dupilumab also nominally significantly reduced airway wall thickness at week 24 versus placebo (least squares mean difference [95% CI], -0.04 mm [-0.07 to -0.01]) and led to reductions in airway wall area and air trapping. Dupilumab improved SAD in patients with moderate to severe asthma.