Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled trial
Gail M. Gauvreau, Roma Sehmi, J Mark FitzGerald, Richard Leigh, Donald W. Cockcroft, Beth E. Davis, Irvin Mayers, Louis‐Philippe Boulet, Dhuha Al‐Sajee, Brittany Salter, Ruth P. Cusack, Terence Ho, Christiane E. Whetstone, Nadia Alsaji, Imran Satia, Kieran J. Killian, Patrick Mitchell, Iain P. Magee, Céline Bergeron, Mohit Bhutani, Viktoría Werkström, Tomasz Durżyński, Kathryn Shoemaker, Rohit Katial, Maria Jison, Paul Newbold, Christopher McCrae, Paul M. O’Byrne
Abstract
BACKGROUND: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma. METHODS: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed. RESULTS: 46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively. CONCLUSION: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.