Abstract
BACKGROUND: Chronic airway inflammation is associated with increased mucus production and airway remodeling and therapies targeting these endpoints are needed. Dupilumab blocks the shared receptor for IL-4/IL-13, drivers of type 2 inflammation. This analysis of VESTIGE (NCT04400318) assesses early treatment responses to dupilumab, 4 weeks after initiation, on airway inflammation, airway dynamics, and mucus score.
METHODS: Patients 21 to 70 years with uncontrolled, moderate-to-severe asthma and elevated type 2 biomarkers (blood eosinophil count ≥300 cells/µL and FeNO ≥25 ppb) were randomized 2:1 to add-on dupilumab 300 mg (n=72) or placebo (n=37) every 2 weeks for 24 weeks. We assessed treatment differences at Week 4 in the proportion of patients achieving FeNO <25 ppb, the least squares mean (LSM) (standard error [SE]) percent change from baseline (BL) in mucus plug score and quantitative CT airway volumes ([s]iVaw) at total lung capacity (TLC), and median percent change in airway resistance ([s]iRaw) at TLC.
RESULTS: By Week 4, patients receiving dupilumab vs placebo were 4 times more likely to achieve FeNO <25 ppb (odds ratio [95%CI]: 4.0 [1.7,9.6]). Patients receiving dupilumab vs placebo showed greater improvements from BL in [s]iVaw (LSM [SE; 95%CI]: 24.2 [29.4; 34.11,82.56] and a greater median reduction in [s]iRaw (−16% vs 6.1%) at TLC at Week 4. Mucus plug score was also reduced from BL at Week 4 (LSM [SE; 95%CI]: −3.0 [0.7; −4.39,−1.63].
CONCLUSION: Dupilumab reduced airway inflammation and mucus plugging, and improved airway volume and flow as early as Week 4 after treatment initiation, and these rapid improvements continued steadily throughout the study duration.
METHODS: Patients 21 to 70 years with uncontrolled, moderate-to-severe asthma and elevated type 2 biomarkers (blood eosinophil count ≥300 cells/µL and FeNO ≥25 ppb) were randomized 2:1 to add-on dupilumab 300 mg (n=72) or placebo (n=37) every 2 weeks for 24 weeks. We assessed treatment differences at Week 4 in the proportion of patients achieving FeNO <25 ppb, the least squares mean (LSM) (standard error [SE]) percent change from baseline (BL) in mucus plug score and quantitative CT airway volumes ([s]iVaw) at total lung capacity (TLC), and median percent change in airway resistance ([s]iRaw) at TLC.
RESULTS: By Week 4, patients receiving dupilumab vs placebo were 4 times more likely to achieve FeNO <25 ppb (odds ratio [95%CI]: 4.0 [1.7,9.6]). Patients receiving dupilumab vs placebo showed greater improvements from BL in [s]iVaw (LSM [SE; 95%CI]: 24.2 [29.4; 34.11,82.56] and a greater median reduction in [s]iRaw (−16% vs 6.1%) at TLC at Week 4. Mucus plug score was also reduced from BL at Week 4 (LSM [SE; 95%CI]: −3.0 [0.7; −4.39,−1.63].
CONCLUSION: Dupilumab reduced airway inflammation and mucus plugging, and improved airway volume and flow as early as Week 4 after treatment initiation, and these rapid improvements continued steadily throughout the study duration.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | PA3933 |
| Tidsskrift | The European Respiratory Journal |
| Vol/bind | 64 |
| Udgave nummer | Suppl. 68 |
| Antal sider | 1 |
| ISSN | 0903-1936 |
| DOI | |
| Status | Udgivet - 2024 |
| Udgivet eksternt | Ja |