Early treatment response to dupilumab on airway inflammation, airway dynamics, and mucus plugging in VESTIGE

<bold>BACKGROUND:</bold> 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 (<ext-link>NCT04400318</ext-link>) assesses early treatment responses to dupilumab, 4 weeks after initiation, on airway inflammation, airway dynamics, and mucus score. <bold>METHODS:</bold> 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. <bold>RESULTS:</bold> 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]. <bold>CONCLUSION:</bold> 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.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa3933
Citations
1
Primary Topic
Eosinophilic Esophagitis
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article
Field-Weighted Citation Impact
0.57
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article

Early treatment response to dupilumab on airway inflammation, airway dynamics, and mucus plugging in VESTIGE

Ana Margarida Pereira, Amelie Rodrigues, Njira Lucia Lugogo, Mario Castro et al.
1 citations
Eosinophilic Esophagitis
0.57
article

Early treatment response to dupilumab on airway inflammation, airway dynamics, and mucus plugging in VESTIGE

Ana Margarida Pereira, Amelie Rodrigues, Njira Lucia Lugogo, Mario Castro, Alberto Papi, Juby A. Jacob‐Nara, Maria Staevska, ARNAUD AB BOURDIN, Christopher Edward Brightling, Charles Fogarty, Lucía De Prado Gómez, Rufai Nadama, Pai-Chien Chou, Francisco Javier González‐Barcala, Celeste Porsbjerg, Liliana Duca, Мykola Ostrovskyy, Mei Zhang, Paul J. Rowe, Harry Sacks, Yamo Deniz, Xavier Soler
article en
1 citations

Abstract

<bold>BACKGROUND:</bold> 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 (<ext-link>NCT04400318</ext-link>) assesses early treatment responses to dupilumab, 4 weeks after initiation, on airway inflammation, airway dynamics, and mucus score. <bold>METHODS:</bold> 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. <bold>RESULTS:</bold> 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]. <bold>CONCLUSION:</bold> 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.

Centre National de la Recherche Scientifique (FR), Ivano-Frankivsk National Medical University (UA), University of Kansas (US), University of Leicester (GB), Inserm (FR), Universidade de Santiago de Compostela (ES), University of Ferrara (IT), University of Michigan (US), Frederiksberg Hospital (DK), Spartanburg Regional Medical Center (US), The University of Kansas Health System (US), Taipei Medical University Hospital (TW), Medical University of Sofia (BG), Transylvania University of Brașov (RO), Physiologie et Médecine Expérimentale du Coeur et des Muscles (FR), Sanofi (Spain) (ES), Honeywell (France) (FR), Sanofi (United States) (US), CUF Porto Hospital (PT), Michigan Medicine (US), Progenics Pharmaceuticals (United States) (US), University of Kansas Medical Center (US), Centre for Health Technology and Services Research (PT), King Khalid University Hospital (SA), Sofia University "St. Kliment Ohridski" (BG), King Khalid University (SA)
Clean water and sanitation
Openalex Percentile: Top 28%
Eosinophilic Esophagitis
0.57
DOISourceOpenAlex
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