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)

Research output: Contribution to journalArticlepeer-review

Abstract

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

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

Methods: After a 4-week run-in period on usual ICS/LABA (baseline), adults with mannitol responsive uncontrolled severe eosinophilic asthma received 3 doses of open label Benra 30mg every 4 weeks followed by 16 weeks washout after the last dose. The primary outcome was doubling difference (DD) in mannitol PD10 at end point after 12 weeks, powered at 90% with n=18 patients required to detect 1 DD. Secondary outcomes included asthma control questionnaire (ACQ) and mini asthma quality of life questionnaire (mini-AQLQ).

Results: 21 patients completed 12 weeks with Benra at end point at week 12. Mean (SEM) age was 53 (4) years, FEV1 80.2 (4.1) %, ICS dose 1895 (59)μg, n=12 on LAMA, n=13 on LTRA. Improvement in AHR was significant by 8 weeks with a mean 2.1 DD (95%CI 1.0, 3.3; p<0.01) change in PD10 at week 12, while mean changes in ACQ and mini-AQLQ 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 improvements occurred in lung function after 12 weeks. Domiciliary peak flow and symptoms were also improved with Benra.

Conclusion: Eosinophil depletion results in clinically meaningful attenuated AHR in severe uncontrolled asthma patients
Original languageEnglish
Number of pages16
JournalJournal of Allergy and Clinical Immunology
Early online date15 Nov 2022
DOIs
Publication statusE-pub ahead of print - 15 Nov 2022

Keywords

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

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