Effect of Dupilumab on Airway Oscillometry, Ventilation/Perfusion, and Mucus Plugging in Moderate-to-Severe Asthma: the VESTIGE Trial

Rationale: Airway remodeling is poorly responsive to current therapies. VESTIGE (NCT04400318), a phase 4 imaging study assessed effects of dupilumab on airway inflammation via lung imaging, spirometry, and airway oscillometry (AO).

Methods: 109 adult patients with uncontrolled Type 2-high moderate-to-severe asthma were randomized to dupilumab 300 mg (n=72) or placebo (PBO) (n=37) q2w for 24 weeks. Endpoints were change from baseline (BL) to Wk 24 in air trapping at FRC, ventilation/perfusion ratio (iV/Q) at TLC, peripheral airway resistance as heterogeneity between 5 ̶ 20 Hz (R5-R20), peripheral compliance as reactance area (AX) using AO, mucus plugging, and pre-BD FEF_25-75%.

Results: BL demographics were comparable in dupilumab and PBO groups. Substantial improvements in iV/Q at TLC in upper/lower lungs were achieved with dupilumab vs PBO at Wk 4, improvements became significant by Wk 24. Dupilumab vs PBO led to significant improvements in small airway dysfunction (SAD), as measured by peripheral airway resistance and compliance, and to significant improvements in mucus plug score (Tab.). Mean differences in peripheral resistance and compliance exceeded their respective biological values (BV) of 0.04 kPa/L/s and 0.39 kPa/L, indicating clinical relevance. In addition, the mean improvement in SAD as measured by FEF_25-75% exceeded the BV of 0.21 L/s.

Conclusions: Dupilumab produced clinically relevant improvements in measures of SAD, including peripheral lung resistance and compliance, FEF_25-75%, along with ameliorated ventilation/perfusion and mucus plugging.

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Publication History

Article published online:
18 March 2025