Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma

Jonathan Corren, Mario Castro, Thomas O'Riordan, Nicola A. Hanania, Ian D. Pavord, Santiago Quirce, Bradley E. Chipps, Sally E. Wenzel, Karthinathan Thangavelu, Megan S. Rice, Sivan Harel, Alexandre Jagerschmidt, Asif H. Khan, Siddhesh Kamat, Jaman Maroni, Paul Rowe, Yufang Lu, Nikhil Amin, Gianluca Pirozzi, Marcella RuddyNeil M.H. Graham, Ariel Teper

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Background: Dupilumab blocks the shared receptor component for IL-4 and IL-13, key drivers of type 2 inflammation, including IgE-mediated allergic inflammation in asthma. In the LIBERTY ASTHMA QUEST (NCT02414854) study, dupilumab reduced severe asthma exacerbations and improved forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers (blood eosinophils and fractional exhaled nitric oxide) at baseline. Objective: We assessed dupilumab's effect on key asthma outcomes in QUEST patients with/without evidence of allergic asthma (total serum IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline). Methods: Severe exacerbation rates and change from baseline in FEV1, asthma control, and markers of type 2 inflammation during the 52-week treatment period were assessed. Results: In the allergic asthma subgroup (n = 1083), dupilumab 200/300 mg every 2 weeks versus placebo reduced severe asthma exacerbation rates (−36.9%/−45.5%; both P < .01), improved FEV1 at week 12 (0.13 L/0.16 L; both P < .001; improvements were evident by the first evaluation at week 2) with greater efficacy observed in patients with elevated type 2 inflammatory biomarkers at baseline, and improved asthma control. Dupilumab treatment also resulted in rapid and sustained reductions in type 2 inflammatory biomarkers. Comparable results were observed in patients without evidence of allergic asthma (n = 819). Conclusion: Dupilumab reduced severe exacerbation rates, improved FEV1 and asthma control, and suppressed type 2 inflammatory biomarkers in patients with uncontrolled, moderate-to-severe asthma with or without evidence of allergic asthma, highlighting the key role of IL-4 and IL-13 in airway inflammation.

Original languageEnglish
Pages (from-to)516-526
Number of pages11
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume8
Issue number2
DOIs
StatePublished - Feb 2020

Keywords

  • ACQ-5
  • Allergic
  • Asthma
  • Biomarkers
  • Dupilumab
  • Exacerbation
  • FEV
  • IL-13
  • IL-4
  • IgE

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