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 M. Salter, Ruth P. Cusack, Terence Ho, Christiane E. Whetstone, Nadia Alsaji, Imran Satia, Kieran J. Killian, Patrick D. Mitchell, Iain P. Magee, Celine Bergeron, Mohit Bhutani, Viktoria Werkström, Tomasz Durżyński, Kathryn Shoemaker, Rohit K. Katial, Maria Jison, Paul Newbold, Christopher McCrae, Paul M. O'Byrne
European Respiratory Journal 2024 64: 2400512; DOI: 10.1183/13993003.00512-2024 

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.