The past, present, and future of monoclonal antibodies to IL-5 and eosinophilic asthma: a review

Abstract

Asthma is a heterogeneous syndrome that might be better described as a constellation of phenotypes or endotypes, each with distinct cellular and molecular mechanisms, rather than as a singular disease. One of these phenotypes is eosinophilic asthma. As the development of eosinophilic inflammation is categorically dependent on the biological activity of Interleukin (IL)-5, IL-5 antagonism became an obvious target for therapy in this phenotype. Early trials of monoclonal antibodies targeting the biological activity of IL-5, including reslizumab, mepolizumab, and benralizumab, were performed on asthmatics with no concern for evidence of eosinophilia. These trials were largely unsuccessful. However, during these trials, researchers recognized the need to quantify eosinophilia in asthma subjects in order to identify those asthmatics in whom these medications would be more likely to improve symptoms and lung function. Using biomarkers, such as sputum and blood eosinophilia, recent studies of these medications have shown improvements in blood and sputum eosinophilia, forced expiratory volume in 1 second, and quality of life assessments as well as reducing occurrences of exacerbations. Moving forward, better and less invasive biomarkers of eosinophilia are necessary to ensure that the correct patients are chosen to receive these medications to receive maximal benefit.

Keywords:

• eosinophilic asthma
• reslizumab
• mepolizumab
• benralizumab
• IL-5
• eosinophils

Disclosure

Dr Megan F Patterson and Dr Larry Borish do not report any conflicts of interest in this work. Dr Joshua L Kennedy has grants to study asthma from the National Institutes of Health (KL2TR000063, UL1TR000039, P20GM103625) and the Arkansas Biosciences Institute.