Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis

William W. Busse, Jorge F. Maspero, Yufang Lu, Jonathan Corren, Nicola A. Hanania, Bradley E. Chipps, Constance H. Katelaris, J. Mark FitzGerald, Santiago Quirce, Linda B. Ford, Megan S. Rice, Siddhesh Kamat, Asif H. Khan, Alexandre Jagerschmidt, Sivan Harel, Paul Rowe, Gianluca Pirozzi, Nikhil Amin, Marcella Ruddy, Neil M.H. GrahamAriel Teper

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Comorbid perennial allergic rhinitis (PAR) or year-round aeroallergen sensitivity substantially contributes to disease burden in patients with asthma. Dupilumab blocks the shared receptor for interleukin (IL) 4 and IL-13, key drivers of type 2 inflammation that play important roles in asthma and PAR. In the LIBERTY ASTHMA QUEST trial (NCT02414854), 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 at baseline (blood eosinophils and fractional exhaled nitric oxide). Objective: To assess dupilumab efficacy in LIBERTY ASTHMA QUEST patients with comorbid PAR. Methods: Severe asthma exacerbation rates, FEV1, asthma control (5-item Asthma Control Questionnaire), rhinoconjunctivitis-specific health-related quality of life (Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores), and type 2 inflammatory biomarkers during the 52-week treatment period were assessed. Results: A total of 814 of the 1902 patients (42.8%) had comorbid PAR (defined as an allergic rhinitis history and ≥1 perennial aeroallergen specific immunoglobulin E (IgE) level ≥0.35 kU/L at baseline). Dupilumab, 200 and 300 mg every 2 weeks, vs placebo reduced severe exacerbations rates by 32.2% and 34.6% (P <.05 for both) and improved FEV1 at week 12 by 0.14 L and 0.18 L (P <.01 for both); greater efficacy was observed in patients with elevated baseline blood eosinophil counts (≥300 cells/μL) and fractional exhaled nitric oxide. Dupilumab treatment also numerically improved the 5-item Asthma Control Questionnaire and Standardized Rhinoconjunctivitis Quality of Life Questionnaire +12 scores and suppressed type 2 inflammatory biomarkers. Conclusion: Dupilumab improved key asthma-related outcomes, asthma control, and rhinoconjunctivitis-specific health-related quality of life while suppressing type 2 inflammatory biomarkers and perennial allergen-specific IgE in patients with moderate-to-severe asthma and comorbid PAR, highlighting its dual inhibitory effects on IL-4 and IL-13 and its role in managing asthma and PAR.

Original languageEnglish
Pages (from-to)565-576.e1
JournalAnnals of Allergy, Asthma and Immunology
Volume125
Issue number5
DOIs
StatePublished - Nov 2020
Externally publishedYes

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