Using biomarkers and independent predictors of therapy response to optimize treatment of uncontrolled severe asthma in the biologic era

Severe asthma is a chronic respiratory disease characterized by a lack of control with maximal standard therapy or exacerbation upon therapy reduction. Recent advances in the diagnosis and management of severe asthma have improved patient outcomes. An improved mechanistic understanding of asthma has revealed that many cases are driven by type 2 inflammation, which can be targeted with biologic agents including omalizumab (anti-IgE), mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5R<i>α</i>), dupilumab (anti-IL-4Rα), and tezepelumab (anti-thymic stromal lymphopoietin). Biomarkers, including elevated fractional exhaled nitric oxide, blood eosinophil counts, and serum IgE levels, have been validated for the diagnosis of severe asthma and can be used to help guide disease management. These biologic agents and biomarkers have changed the clinical management of severe asthma, making it possible to pursue the goal of clinical remission. However, despite these advances, a proportion of patients continue to experience uncontrolled severe asthma, which has significant implications for disease management and quality of life. In this review, I briefly examine the current state of biologics and biomarkers in the treatment of uncontrolled severe asthma, and draw on my clinical experience to highlight limitations to optimal management, including persistent treatment heterogeneity. After discussing emerging biomarkers and predictors of disease status and treatment response, I provide my perspective on future approaches and research directions that may enhance clinical treatment and improve patient outcomes.