Anti-cytokine biologics for asthma in adults

Abstract

An estimated 3–10% of patients with asthma are unable to reach full control with currently available inhaled therapies. In a large proportion of these patients, asthma can be driven in whole or in part by type 2 (T2) inflammation, which is usually initiated by an immunological response to stimulation at mucosal surfaces. The introduction of monoclonal antibodies, which target T2 inflammatory processes, provides important options for this population. In the past decade, five anticytokine biologics (ACBs) that block specific T2 inflammatory cytokines have been introduced. Three biologics, mepolizumab, reslizumab, and benralizumab, inhibit the IL-5 or IL-5 receptor pathway; dupilumab blocks IL-4 and IL-13 through its activity on the IL-4 receptor-alpha; and tezepelumab prevents activation of the thymic stromal lymphopoietin cytokine production cascade. These drugs reduce exacerbations and improve lung function and patient-reported asthma quality of life in individuals with a history of asthma exacerbations and evidence of T2 inflammation. Some also allow oral corticosteroid reduction or elimination in patients dependent on these therapies for asthma control. The effect of ACBs varies by the degree of T2 inflammation, which is most easily assessed by blood eosinophil counts and exhaled nitric oxide. The use of ACBs guided by these biomarkers and phenotypic characteristics of patients with severe asthma allows a personalised medicine approach that increases the likelihood of improvement.