Eosinophil depletion with benralizumab is associated with attenuated mannitol airway hyperresponsiveness in severe uncontrolled eosinophilic asthma

Rory Chan, Chris RuiWen Kuo, Sunny Jabbal, Brian Lipworth (Lead / Corresponding author)

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    12 Citations (Scopus)
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    Abstract

    Background: Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma.

    Objective: We investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design.

    Methods: After a 4-week run-in period with provision of usual inhaled corticosteroids and/or long-acting β-agonist (baseline), adults with mannitol-responsive uncontrolled severe eosinophilic asthma received 3 doses of open-label benralizumab 30 mg every 4 weeks, followed by 16 weeks’ washout after the last dose. The primary outcome was doubling difference (DD) in provocative dose of mannitol required to decrease FEV 1 by 10% (PD 10) at the end point after 12 weeks, powered at 90% with 18 patients required to detect 1 DD. Secondary outcomes included measures assessed by the asthma control questionnaire and mini-asthma quality of life questionnaire.

    Results: Twenty-one patients completed 12 weeks’ benralizumab therapy at the end point at week 12. Mean (SEM) age was 53 (4) years, and FEV 1 80.2% (4.1%) inhaled corticosteroid dose was 1895 (59) μg, with 12 receiving long-acting muscarinic antagonist and 13 leukotriene receptor antagonists. Improvement in AHR was significant by 8 weeks, with a mean 2.1 DD (95% confidence interval 1.0, 3.3; P <.01) change in PD 10 at week 12, while mean changes in asthma control questionnaire and mini-asthma quality of life questionnaire were significant by week 2 and sustained over 12 weeks, both exceeding the minimal important difference. Peripheral blood eosinophils were depleted by 2 weeks (439 to 6 cells/μL). No significant improvement occurred in lung function after 12 weeks. Domiciliary peak flow and symptoms also improved with benralizumab.

    Conclusion: Eosinophil depletion results in clinically meaningful attenuated AHR in severe uncontrolled asthma patients.

    Original languageEnglish
    Pages (from-to)700-705.e10
    Number of pages16
    JournalJournal of Allergy and Clinical Immunology
    Volume151
    Issue number3
    Early online date16 Nov 2022
    DOIs
    Publication statusPublished - 3 Mar 2023

    Keywords

    • Airway hyperresponsiveness
    • asthma control
    • benralizumab
    • mannitol
    • quality of life
    • severe asthma

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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