Role of Targeted Biologic Therapies in the Management of Severe Asthma: A Review

Abstract

Severe asthma is a heterogeneous respiratory disorder characterized by persistent symptoms, recurrent exacerbations, airflow limitation, and inadequate disease control despite optimized standard therapy. Although it affects a relatively small proportion of patients with asthma, it accounts for a substantial burden of morbidity, mortality, healthcare utilization, and reduced quality of life. Advances in asthma immunopathology have led to the identification of distinct inflammatory endotypes, particularly Type 2 (T2)-high and non-Type 2 asthma, facilitating the development of targeted biologic therapies. This review summarizes the current understanding of severe asthma pathogenesis, emphasizing the roles of key inflammatory mediators, including immunoglobulin E (IgE), interleukin (IL)-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP), and IL-33. The mechanisms of action, clinical efficacy, safety, and corticosteroid- sparing benefits of approved biologic agents, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, are comprehensively reviewed. Particular attention is given to biomarker-guided patient selection and precision medicine approaches that optimize therapeutic outcomes. Emerging biologic therapies, strategies for biologic switching and discontinuation, and recent international guideline recommendations are also reviewed. Furthermore, future perspectives involving multi-omics technologies, artificial intelligence, and digital health tools are highlighted. Overall, biologic therapies have transformed the management of severe asthma by enabling more individualized treatment strategies, improving disease control, reducing exacerbation risk, and enhancing long-term clinical outcomes.