The Current State of Biologic Therapies for Treatment of Refractory Asthma
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The Current State of Biologic Therapies for Treatment of Refractory Asthma Matthew Mavissakalian 1 & Sean Brady 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Asthma is a heterogeneous disease, with the immune processes behind the chronic inflammation underlying this disorder differing between the various identified asthma endotypes. In addition to heterogeneity in underlying disease pathophysiology, asthmatics fall across a broad spectrum of disease severity and can vary greatly in their response to convention asthma therapies. A small percentage of patients with severe persistent asthma will remain uncontrolled despite treatment with high-dose inhaled corticosteroids and a long-acting beta-agonist. Less than two decades ago, there were few options for these treatment-refractory asthmatics beyond chronic systemic steroids, with their myriad of treatment-limiting side effects. However, in recent years, there have been a growing number of Food and Drug Administration (FDA)–approved biologic medications with targets that include immunoglobulin E (IgE), interleukin-5 (IL-5), the IL-5 receptor and the IL-4/IL-13 receptor-alpha subunit. The current FDAapproved biologics for severe persistent asthma are omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. These monoclonal antibodies have been shown to improve asthma control, decrease asthma exacerbations and decrease glucocorticoid dependence in certain subsets of patients with asthma. The optimal biologic for treatment of severe asthma varies from patient to patient, depending on the underlying pathophysiology of the patient’s disease. For each of these medications, there are certain biomarkers that can help predict whether a patient is likely to respond favorably to the medication. This review will discuss the currently approved biologics for severe persistent asthma, including their indications, efficacy and side effects. Keywords Asthma . Biologic therapies . Asthma medications . Eosinophils . IgE . IL-5 . IL-4 . IL-13 . Thymic stromal lymphopoietin (TSLP) . Omalizumab . Mepolizumab . Reslizumab . Benralizumab . Dupilumab
Introduction Asthma was described by Hippocrates nearly 2500 year ago. [1] It received an official definition in 1958 by the CIBA Guest Symposium as “the condition of subjects with widespread narrowing of the bronchial airways, which changes its severity over time spontaneously or under treatment, and is not due to cardiovascular disease.” [2] Included in the definition were characteristics such as “abnormal breathlessness, which may be paroxysmal or persistent, wheezing, and in most cases, relief by bronchodilator drugs (including glucocorticoids).” As asthma has been studied in more depth, it has become apparent that it is a heterogeneous condition that does
* Sean Brady [email protected] 1
Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 100 High Street, Buffalo, NY 14203, USA
not respond in the
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