The Role of Monoclonal Antibodies in the Management of Severe Asthma and Eosinophilic COPD

Severe asthma and chronic obstructive pulmonary disease (COPD) represent a significant global health burden, with a substantial subset of patients remaining uncontrolled despite maximal standard-of-care therapies. The advent of biologic therapies has heralded a paradigm shift in the management of these conditions, moving from a broad, phenotype-based approach to a precise, endotype-driven strategy targeting specific pathophysiological mechanisms. This review discusses the current understanding and evidence for biologic agents in severe obstructive airway disease. It first delineates the immunological basis for targeted therapy, focusing on the central role of the Type 2 (T2) inflammatory cascade, initiated by epithelial alarmins and driven by key cytokines such as interleukin (IL)-4, IL-5, and IL-13. This common pathway provides the rationale for targeting T2 inflammation not only in severe asthma but also in the newly recognized eosinophilic phenotype of COPD. A comprehensive overview of biologics approved for severe asthma is presented, evaluating the data for agents targeting immunoglobulin E (omalizumab), the IL-5 pathway (mepolizumab, reslizumab, benralizumab), the IL-4/IL-13 axis (dupilumab), and the upstream alarmin thymic stromal lymphopoietin (TSLP) (tezepelumab). The review then appraises the recent and transformative application of these therapies to COPD, analyzing the mixed results of anti-IL-5 agents and the landmark success of dupilumab, which has established a new treatment paradigm for eosinophilic COPD. The pivotal role of biomarkers—including blood eosinophil count, fractional exhaled nitric oxide (FeNO), and serum IgE—in guiding patient selection and personalizing therapy is examined. Finally, the article looks to the future, exploring novel molecular targets such as IL-33, the potential of innovative delivery systems like inhaled biologics, and the evolution of therapeutic goals from symptom control toward disease modification and clinical remission.