DUPILUMAB REDUCES MUCUS BURDEN IRRESPECTIVE OF BASELINE RESPIRATORY CHARACTERISTICS IN PATIENTS WITH UNCONTROLLED MODERATE-TO-SEVERE ASTHMA: RESULTS FROM THE VESTIGE STUDY

LUIS PÉREZ DE LLANO; ELEANOR Dunican; NJIRA L Lugogo; MARIO Castro; ALBERTO Papi; ARNAUD Bourdin; ALEJANDRO P Comellas; ARMAN Altincatal; REBECCA Gall; HASHEM Awad; SURYA P Bhatt

doi:10.1016/j.chest.2025.09.073

PURPOSE: In severe asthma mucus plugs are associated with airflow obstruction and impaired lung function. Dupilumab is a fully human monoclonal antibody that blocks interleukin (IL)-4 and IL-13 signaling. In the randomized, placebo-controlled VESTIGE study (NCT04400318), dupilumab treatment reduced airway inflammation and mucus plugging in patients with moderate-to-severe type 2 asthma. This post hoc analysis of VESTIGE assessed the reduction in mucus burden after dupilumab treatment according to the patients’ baseline pre-bronchodilator ppFEV1and FeNO values. METHODS: VESTIGE was an international, randomized, double-blind, placebo-controlled, phase 4 trial that included 109 adults aged 21 to 70 years with uncontrolled moderate-to-severe asthma (defined as 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 previous year) and type 2 inflammation (defined as blood eosinophil count ≥300 cells/μL and fractional exhaled nitric oxide [FeNO] ≥25 parts per billion [ppb]). Patients were randomized 2:1 to receive dupilumab 300 mg (n=72) or placebo (n=37) every 2 weeks for 24 weeks. We evaluated changes from baseline to Week 24 in global lung mucus plug score (range: 0–18; measured by quantifying completely occluded bronchopulmonary segments using pre-bronchodilator multidetector computed tomography scan imaging) and global lung mucus volume (measured by voxel quantification of all detectable mucus plugs). Data were analyzed by subgroups stratified by pre-bronchodilator ppFEV1 (<60% and 60%–80%) or FeNO levels (<50 ppb and ≥50 ppb) at study baseline. RESULTS: From baseline to Week 24, patients receiving dupilumab showed a significantly greater reduction in mucus plug scores compared to placebo in both the baseline pre-bronchodilator ppFEV1 <60%, (least squares [LS] mean difference [95% confidence interval (CI)] dupilumab vs placebo: -4.22 [-6.63, -1.81]; P<0.01) and pre-bronchodilator ppFEV1 60%–80% subgroups (-4.71 [-7.13, -2.29]; P<0.001). Similar results were observed in patients with baseline FeNO <50 (-5.09 [-7.10, -3.09]; P<0.001) and ≥50 ppb (-3.22 [-6.21, -0.24]; P<0.05). Reductions in mucus volume were also significantly greater in patients receiving dupilumab vs placebo in baseline pre-bronchodilator ppFEV1 <60% (-0.07 mL [-0.11, -0.02]; P<0.01) and 60%–80% subgroups (-0.14 mL [-0.21, -0.07]; P<0.001). Similar results were seen for baseline FeNO <50 (-0.12 mL [-0.18, -0.05]; P<0.001) and ≥50 ppb (-0.07 mL [-0.12, -0.02]; P<0.01). CONCLUSIONS: Dupilumab reduced mucus plug score and volume in patients with uncontrolled moderate-to-severe asthma and type 2 inflammation irrespective of baseline pre-bronchodilator ppFEV1 value (<60% or 60%–80%) and baseline FeNO level (<50 ppb or ≥50 ppb). CLINICAL IMPLICATIONS: Regardless of patients’ baseline pre-bronchodilator ppFEV1and FeNO values, dupilumab treatment can improve mucus burden in adults with moderate-to-severe asthma.

DUPILUMAB REDUCES MUCUS BURDEN IRRESPECTIVE OF BASELINE RESPIRATORY CHARACTERISTICS IN PATIENTS WITH UNCONTROLLED MODERATE-TO-SEVERE ASTHMA: RESULTS FROM THE VESTIGE STUDY

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