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

• DOI: 10.1016/j.jaci.2022.10.028
• Publication Date: 2022-11-16T06:30:33Z
• Authors: Rory Chan; Chris RuiWen Kuo; Sunny Jabbal; Brian J. Lipworth
• Keywords: Benralizumab; Airway hyperresponsiveness; Clinical endpoint

Airway hyperresponsiveness (AHR) and eosinophilia are hallmarks of persistent asthma.We investigated whether eosinophil depletion with benralizumab might attenuate indirect mannitol AHR in severe uncontrolled asthma using a pragmatic open-label design.After 4-week run-in period provision usual inhaled corticosteroids and/or long-acting β-agonist (baseline), adults mannitol-responsive eosinophilic received 3 doses 30 mg every 4 weeks, followed by 16 weeks' washout after the last dose. The primary outcome was doubling difference (DD) provocative dose required to decrease FEV1 10% (PD10) at end point 12 powered 90% 18 patients detect 1 DD. Secondary outcomes included measures assessed control questionnaire mini-asthma quality life questionnaire.Twenty-one completed therapy week 12. Mean (SEM) age 53 (4) years, 80.2% (4.1%) corticosteroid 1895 (59) μg, receiving muscarinic antagonist 13 leukotriene receptor antagonists. Improvement significant 8 mean 2.1 DD (95% confidence interval 1.0, 3.3; P < .01) change PD10 12, while changes were 2 sustained over both exceeding minimal important difference. Peripheral blood eosinophils depleted weeks (439 6 cells/μL). No improvement occurred lung function weeks. Domiciliary peak flow symptoms also improved benralizumab.Eosinophil results clinically meaningful attenuated patients.