Targeting Eosinophils in Asthmatic Inflammation: Benefits and Drawbacks.

Abstract

Asthma is associated with eosinophilic airway inflammation which contributes to poor asthma outcomes in a subset of severe asthmatics. This review traces the scientific rationale as well as the clinical development of novel therapeutics to target either IL-5 or the IL-5α receptor to deplete eosinophils from the airway to improve asthma outcomes in severe asthma with eosinophilic airway inflammation. The importance of IL-5 to eosinophil growth, survival, and function was initially identified in mice, and has been confirmed in studies of human eosinophils. As both IL-5 and the IL-5α receptor were identified as therapeutic targets to deplete eosinophils in the airway in asthmatics, humanized IgG antibodies were developed to target either IL-5 or the IL-5α receptor in eosinophilic asthma. The current availability of three biologics that deplete eosinophils (mepolizumab, reslizumab, and benralizumab) has provided a novel therapeutic approach to treat severe asthma with eosinophilic inflammation not controlled by inhaled corticosteroids in combination with long acting bronchodilators. Two of these eosinophil targeted biologics (mepolizumab, reslizumab) target IL-5 an eosinophil growth factor, while the third eosinophil targeted biologic (benralizumab) targets the IL-5α receptor expressed by eosinophils. Each of these eosinophil targeted therapies significantly deplete eosinophils in the blood, sputum, and airway and are associated with a significant approximately 50% reduction in asthma exacerbations in most studies without significant side effects. In addition, selected studies have shown that eosinophil targeted biologics improve asthma symptom quality of life scores and lung function. At present, there are no direct head to head comparison studies to determine whether any of the three eosinophil targeted biologics has a better asthma outcome profile/safety profile. The development of eosinophil targeted biologics has been a significant advance in the treatment of severe asthma with eosinophilic inflammation.