Pneumologie 2020; 74(S 01): 89
DOI: 10.1055/s-0039-3403257
Posterbegehung (PO17) – Sektion Allergologie und Immunologie
Posterbegehung der Sektion Allergologie und Immunologie
Georg Thieme Verlag KG Stuttgart · New York

Dupilumab Efficacy in Patients With Uncontrolled, Moderate-to-Severe Asthma and Serologic Evidence of Allergic Bronchopulmonary Aspergillosis

J Corren
1   David Geffen School of Medicine at Ucla
,
L Sher
2   Peninsula Research Associates
,
X Zhu
3   Regeneron Pharmaceuticals, Inc.
,
MS Rice
4   Sanofi
,
Y Deniz
3   Regeneron Pharmaceuticals, Inc.
,
P Rowe
4   Sanofi
,
HW Staudinger
4   Sanofi
,
M Ruddy
3   Regeneron Pharmaceuticals, Inc.
,
N Patel
4   Sanofi
,
NMH Graham
3   Regeneron Pharmaceuticals, Inc.
,
A Teper
4   Sanofi
,
N Amin
3   Regeneron Pharmaceuticals, Inc.
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

Also available at
 

Background: Dupilumab, a fully human VelocImmune®-derived monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2W) vs. placebo reduced severe exacerbations and improved pre-bronchodilator forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated baseline type 2 biomarkers. Allergic bronchopulmonary aspergillosis (ABPA) is characterized by Aspergillus fumigatus hypersensitivity and robust type 2 inflammatory responses leading to poor asthma control and airway fibrosis. This post hoc analysis assessed dupilumabʼs efficacy in patients with serologic evidence of ABPA (baseline serum total IgE > 1,000 IU/mL, serum IgE-A. fumigatus > 0.35 IU/mL, blood eosinophils > 500 cells/µL).

Methods: Annualized severe exacerbation rates during the 52-week treatment period were analyzed using negative binomial regression models; least squares mean change in FEV1 from baseline to Weeks 24 and 52 using mixed-effect models with repeated measures; and total IgE, IgE-A. fumigatus, and fractional exhaled nitric oxide (FeNO) at Week 52 using Wilcoxon rank-sum test.

Results: Dupilumab 200/300 mg combined q2w vs. placebo reduced annualized severe exacerbation rates by 81% (P = 0.01) and improved pre-bronchodilator FEV1 by 0.26 L (P = 0.09) and 0.33 L (P = 0.07) at Weeks 24 and 52, respectively. Dupilumab significantly reduced total IgE (median % change: − 75.65% vs. − 19.65%; P < 0.01), IgE-A. fumigatus (− 74.85% vs. − 40.44%; P = 0.01), and FeNO (− 60.00% vs. − 24.29%; P = 0.03). In the overall population, the most frequent dupilumab vs. placebo adverse event was injection-site reaction (15%/18% vs. 5%/10%).

Conclusion: Dupilumab reduced severe exacerbations, improved lung function, and reduced type 2 inflammatory biomarkers in patients with uncontrolled, moderate-to-severe asthma and serologic evidence of ABPA.