Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders

Abstract

Purpose of reviewHuman eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin. Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines.Recent findingsEosinophils are the major source of interleukin-5 and highly express the interleukin-5Rα on their surface. Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5Rα (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD). Overall, targeting interleukin-5/interleukin-5Rα is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma. Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA. A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD.SummaryThe review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD. Interleukin-5/interleukin-5Rα-targeted treatments offer promises to patients with eosinophilic respiratory disorders.

Nordic consensus statement on the systematic assessment and management of possible severe asthma in adults

“…Importantly, the major advances in the management of severe asthma are associated with phenotypes of Type 2-high asthma (e.g. atopic and eosinophilic phenotypes) [163,164], whereas both predictive biomarkers and treatments for asthmatics, whose disease does not show presence of the type 2 inflammation are very limited. Furthermore, it is important to mention that the phenotyping, endotyping, and selecting biomarkers for the personalized approach do not necessarily include single biomolecules, but rather be composed of properly selected constellations or signatures of proteins and other peptides, transcriptomes, genes, microRNAs [164] and metabolites [165,166].…”

“…atopic and eosinophilic phenotypes) [163,164], whereas both predictive biomarkers and treatments for asthmatics, whose disease does not show presence of the type 2 inflammation are very limited. Furthermore, it is important to mention that the phenotyping, endotyping, and selecting biomarkers for the personalized approach do not necessarily include single biomolecules, but rather be composed of properly selected constellations or signatures of proteins and other peptides, transcriptomes, genes, microRNAs [164] and metabolites [165,166]. Finally, there is a need for more evidence on the consistency of severe asthma phenotypes, throughout the clinical course of severe asthma [23,159,163,167–169].…”

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“…There was no decrease in the medication dose in the placebo group. In 2015, the FDA in the United States and the European EMA approved mepolizumab as maintenance therapy in severe eosinophilic BA in adults [31].…”

“…Eosinophils induce the secretion of cytokines by Th2 cells [13]. There is growing evidence that eosinophilic inflammation is a sign of BA, and its formation is associated with elevated levels of IL-5 in the bronchi of these patients [16]. The mechanisms of the eosinophilic type of BA include stimulation of Th2 by allergens, which is accompanied by the release of cytokines (IL-4, -5, -9, -13).…”

“…There was no decrease in the medication dose in the placebo group. In 2015, the FDA in the United States and the European EMA approved mepolizumab as maintenance therapy in severe eosinophilic BA in adults [31].Reslizumab is a humanized monoclonal antibody to IL-5. Castro M et al [32] used reslizumab to treat 53 adult patients with severe eosinophilic asthma.…”