Abstract Rationale The type 2 cytokines interleukin (IL)-4 and IL-13 promote mucus overproduction and plugging, contributing to airflow limitation in asthma. Dupilumab is a fully human monoclonal antibody that blocks IL-4 and IL-13 signaling. This post hoc analysis of the VESTIGE study (NCT04400318) evaluated reductions in mucus score and volume following dupilumab treatment in subgroups stratified by baseline exacerbation history and lung function. Methods In the phase 4 VESTIGE trial, 109 adults aged 21-70 years with uncontrolled moderate-to-severe asthma (5-item Asthma Control Questionnaire score ≥1.5, pre-bronchodilator percent predicted forced expiratory volume in 1 second ppFEV1 ≤80%, and ≥1 asthma exacerbation in the previous year) and type 2 inflammation (blood eosinophil count ≥300 cells/μL and fractional exhaled nitric oxide ≥25 parts per billion) were randomized 2:1 to receive dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Mucus plug scores were measured using multidetector CT scans; the number of completely occluded bronchopulmonary segments was quantified (score 0-18). Mucus volume was calculated by voxel quantification of all detectable mucus plugs. Outcomes were evaluated in patient subgroups with 1 or 2 severe asthma exacerbations in the year prior to the study, subgroups with baseline pre-bronchodilator forced expiratory volume in 1 second FEV1 ≤1.75 L or 1.75 L, and subgroups with baseline pre-bronchodilator ppFEV1 60% or 60-80%. Results At Week 24, the reduction in mucus score from baseline was significantly greater for dupilumab than for placebo, regardless of baseline severe exacerbation history or lung function (Table). Decreases in mucus volume were significantly greater with dupilumab than with placebo across all baseline exacerbation history and lung function groups (Table). Conclusion Dupilumab reduced mucus plug score and volume in patients with uncontrolled moderate-to-severe asthma and type 2 inflammation, regardless of baseline exacerbation history or lung function. This abstract is funded by: Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifier: NCT04400318
Castro et al. (Fri,) studied this question.