ASTHMA, a chronic inflammatory disease, causes variable airflow limitation and often involves eosinophilic airway inflammation, particularly in allergic asthma triggered by allergens. This subtype predominantly affects younger individuals. Eosinophils, a type of white blood cell, contribute significantly to airway inflammation, particularly during the late asthmatic response (LAR), which follows an allergen-induced early asthmatic response (EAR). The LAR is associated with prolonged airway hyperresponsiveness and increased eosinophilia.
Benralizumab, a monoclonal antibody targeting the interleukin-5 receptor alpha (IL-5Rα), induces near-complete eosinophil and basophil depletion through antibody-dependent cell-mediated cytotoxicity. It has shown efficacy in reducing asthma exacerbations, controlling symptoms, and decreasing systemic corticosteroid dependence in severe eosinophilic asthma. Despite its success in depleting eosinophils and basophils in blood, bone marrow, and sputum, its effect on allergen-induced LAR in mild allergic asthma remains unclear.
In a recent study, benralizumab administered over eight weeks significantly reduced eosinophil counts in blood and sputum and attenuated allergen-induced sputum eosinophilia. However, it did not influence the allergen-induced LAR, suggesting that eosinophils are not critical drivers of allergen-induced bronchoconstriction in mild asthma. This aligns with findings from prior studies using mepolizumab, another anti-IL-5 antibody, which also failed to impact the LAR despite reducing eosinophils.
Other studies highlight the role of mast cells and basophils in LAR through their release of mediators such as histamine and cysteinyl leukotrienes. Pharmacological agents targeting these mediators have partially attenuated EAR and fully inhibited LAR, reinforcing their potential involvement in allergen-induced airway responses.
In conclusion, while benralizumab effectively reduces eosinophil levels, its lack of impact on the LAR suggests that other cell types, such as mast cells and basophils, may play a more significant role in allergen-induced airway responses in mild asthma. Future research should explore these mechanisms to enhance understanding and refine treatment strategies for allergic asthma.
Katie Wright, EMJ
Reference
Gauvreau GM et al. Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled trial. Eur Respir J. 2024;64(3):2400512.
