Dupilumab Improves Lung Function and Asthma Control While Reducing Systemic Corticosteroid Use in Patients With Allergic Bronchopulmonary Aspergillosis: The Phase 2 LIBERTY ABPA AIRED Study
Author(s)
Arnaud Bourdin, MD, PhD1, Jonathan Corren, MD2, Anand Shah, MD3, Caroline G. Baxter, MD4, Lavina Davidescu, MD, PhD5, Heather Paleczny, BS6, Joseph Chiarappa, PhD6, Andrew Fontenot, MD6, Paula Dakin, MBChB6, Elizabeth Laws, PhD7, Jennifer Maloney, MD6, Lacey B. Robinson, MD7, Allen Radin, MD6.
1PhyMedExp, University of Montpellier, Montpellier, France, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 3Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 4Manchester University NHS Foundation Trust, Manchester, United Kingdom, 5University of Oradea, Oradea, Romania, 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, 7Sanofi, Cambridge, MA, USA.
1PhyMedExp, University of Montpellier, Montpellier, France, 2David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, 3Royal Brompton and Harefield Hospitals, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 4Manchester University NHS Foundation Trust, Manchester, United Kingdom, 5University of Oradea, Oradea, Romania, 6Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA, 7Sanofi, Cambridge, MA, USA.
OBJECTIVES: ABPA, driven by type 2 inflammation, is characterized by hypersensitivity to Aspergillus fumigatus following airway colonization in patients with asthma. Current ABPA therapies have adverse effects and do not address the immunological basis of ABPA. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins 4/13, key and central drivers of type 2 inflammation. The phase 2 LIBERTY ABPA AIRED study (NCT04442269) evaluated dupilumab efficacy in patients with ABPA.
METHODS: 62 adults with asthma and ABPA per International Society for Human and Animal Mycology (ISHAM) criteria were randomized to receive dupilumab 300 mg (n=35) or placebo (n=27) every 2 weeks for 24 to 52 weeks. Primary endpoint: change from baseline to Week 24 in pre-bronchodilator forced expiratory volume in 1 second (FEV1), assessed through formal hypothesis testing. Other endpoints: annualized rate of severe respiratory exacerbations, change from baseline in St. George’s Respiratory Questionnaire (SGRQ) score, and proportion of patients with ≥50% reduction in systemic corticosteroid (SCS) dose, assessed through within-group, descriptive statistics.
RESULTS: Change from baseline in pre-bronchodilator FEV1 at Week 24 was significantly greater for dupilumab vs placebo (LS mean difference [95% CI]: 0.201 L [0.077, 0.326]; P=0.002). Dupilumab vs placebo reduced severe respiratory exacerbations by 55.2%, with adjusted annualized rates (95% CI) of 0.695 (0.355, 1.360) vs 1.551 (0.747, 3.218) events per person-year. Patients receiving dupilumab achieved a >12 mean point reduction in SGRQ score at each post-baseline timepoint vs the largest mean reduction of 9.46 points at Week 12 in patients receiving placebo. At Week 24, 85.7% of patients on SCS at baseline who received dupilumab reduced SCS dosage by ≥50% vs 28.6% of patients receiving placebo.
CONCLUSIONS: Dupilumab significantly improved lung function and substantially reduced severe exacerbations while enhancing quality of life and reducing SCS use in patients with ABPA and asthma.
METHODS: 62 adults with asthma and ABPA per International Society for Human and Animal Mycology (ISHAM) criteria were randomized to receive dupilumab 300 mg (n=35) or placebo (n=27) every 2 weeks for 24 to 52 weeks. Primary endpoint: change from baseline to Week 24 in pre-bronchodilator forced expiratory volume in 1 second (FEV1), assessed through formal hypothesis testing. Other endpoints: annualized rate of severe respiratory exacerbations, change from baseline in St. George’s Respiratory Questionnaire (SGRQ) score, and proportion of patients with ≥50% reduction in systemic corticosteroid (SCS) dose, assessed through within-group, descriptive statistics.
RESULTS: Change from baseline in pre-bronchodilator FEV1 at Week 24 was significantly greater for dupilumab vs placebo (LS mean difference [95% CI]: 0.201 L [0.077, 0.326]; P=0.002). Dupilumab vs placebo reduced severe respiratory exacerbations by 55.2%, with adjusted annualized rates (95% CI) of 0.695 (0.355, 1.360) vs 1.551 (0.747, 3.218) events per person-year. Patients receiving dupilumab achieved a >12 mean point reduction in SGRQ score at each post-baseline timepoint vs the largest mean reduction of 9.46 points at Week 12 in patients receiving placebo. At Week 24, 85.7% of patients on SCS at baseline who received dupilumab reduced SCS dosage by ≥50% vs 28.6% of patients receiving placebo.
CONCLUSIONS: Dupilumab significantly improved lung function and substantially reduced severe exacerbations while enhancing quality of life and reducing SCS use in patients with ABPA and asthma.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO78
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)