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.

Regulating Bcl2L12 expression in mast cells inhibits food allergy

“…Over production of Th2 cytokines is one of the features of allergic diseases and some other inflammations 29. IL-5 is the key cytokine to promote the development of eosinophils 30. The present data add novel information to the characteristics of IL-5; IL-5 not only regulates eosinophil development, but it also regulates mast cell activities by inducing the expression of Bcl2L12 in mast cells.…”

Modulating Th2 Cell Immunity for the Treatment of Asthma

“…Three different biologic drugs targeting IL-5 signaling are available, and FDA-approved. All three treatments have been consistently shown to reduce blood eosinophil counts and sputum eosinophils ( 47 , 52 , 53 ). Mepolizumab is a humanized IgG1 monoclonal antibody that recognizes and blocks IL-5 and prevents its binding to IL-5 receptor alpha subunit (IL-5Rα or CD125) on the surface of eosinophils.…”

European Respiratory Society International Congress 2018: Allied Respiratory Professionals’ report of highlighted sessions

“…[6] and their study that indicated that dyspnoea is a better predictor of 5-year survival than measures of airways obstruction in patients with COPD. In eosinophilic asthmatics, mepolizumab has been shown to improve exacerbation rates but does not show any consistent effect on objective measures such as FEV 1 [7, 8]. O. Usmani referenced the clinical utility of forced vital capacity (FVC) (measured during the same manoeuvre as FEV 1 ).…”