New Anti-Eosinophil Drugs for Asthma and COPD: Targeting the Trait!
Asthma and COPD are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and they are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade, several monoclonal antibodies and small molecule therapies have been developed to target this trait. These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, and benralizumab), IL-13 (lebrikizumab and tralokinumab), IL-4 receptor alpha (dupilumab), IgE (omalizumab), and anti-thymic stromal lymphopoietin (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant and timapiprant). Although these novel biologic agents have shown promising results in many patients with asthma and COPD who have eosinophilic airway inflammation, it is evident that not all patients respond equally well, despite similar clinical, functional, and inflammatory characteristics. This heterogeneity in treatment response is probably related to different molecular pathways or endotypes leading to eosinophilic airway inflammation, including adaptive immune pathways mediated by T helper 2 cells and innate immune pathways mediated by innate lymphoid cells. The relative contribution of these pathways in asthma and COPD is not yet clarified, and there are currently no reliable biomarkers that represent the various pathways. Therefore, there is an urgent need for easily measurable and reproducible biomarkers that are linked to underlying pathophysiologic disease mechanisms and can predict and monitor responses to novel biologic agents.