Monoclonal antibodies targeting inflammatory pathways in chronic obstructive pulmonary disease: Evidence and...

Chronic obstructive pulmonary disease (COPD) is a common and heterogeneous inflammatory lung disease associated with exacerbations that drive morbidity, mortality, and health care utilization worldwide. Although inhaled therapies remain the cornerstone of treatment, many patients continue to experience exacerbations despite optimized therapy, highlighting the need for new targeted approaches. Advances in understanding COPD immunopathology have identified several inflammatory pathways that may be amenable to monoclonal antibody therapies. Traditionally, COPD has been associated with neutrophilic inflammation linked to type-1 and type-3 immune responses. However, clinical trials targeting these pathways, including tumor necrosis factor, interleukin (IL)-1β, and IL-17, have largely failed to demonstrate clinical benefit. In contrast, increasing evidence supports a role for type-2 inflammation and upstream pathways in a subset of patients with COPD, including individuals without a history of asthma. Biomarkers such as blood eosinophils and fractional exhaled nitric oxide can help identify this endotype and guide therapeutic selection. Randomized trials of monoclonal antibodies suppressing inflammatory pathways have demonstrated reductions in exacerbations among carefully selected patients with eosinophilic COPD, leading to the recent recommendation of dupilumab and mepolizumab in international treatment guidelines. Emerging strategies are exploring upstream epithelial mediators, including alarmins such as IL-33, thymic stromal lymphopoietin, and bispecific therapies that suppress multiple inflammatory pathways. A consistent finding is that patients with moderate (nonsevere) COPD and concomitantly elevated blood eosinophils and fractional exhaled nitric oxide derive greater benefit from monoclonal antibodies. These developments suggest that targeted monoclonal antibody therapy may play an expanding role in COPD management, supporting the concept of earlier intervention in high-risk COPD.