Biologics in Chronic Obstructive Pulmonary Disease: Current Status and Future Prospects.

Significant progress has been made in managing chronic obstructive pulmonary disease (COPD), yet substantial unmet needs persist due to the disease's heterogeneity and the diverse underlying inflammatory mechanisms. Recent advances have broadened our understanding of COPD beyond a single pathophysiologic model, leading to the development of biologic therapies that target specific immune pathways. This review summarizes current evidence from clinical trials involving biologics in COPD. Early efforts to inhibit non-type 2 inflammation yielded limited results, highlighting the necessity for more refined, endotype-based approaches. Subsequent phase 3 trials have shown considerable clinical benefits in specific patient subsets: dupilumab, which blocks interleukin (IL)-4 and IL-13 signaling, and mepolizumab, which targets IL-5, consistently reduced exacerbation frequency among patients with high blood eosinophil counts (≥300 cells/μL). In contrast, other biologics-such as benralizumab, tezepelumab, and IL-33/suppression of tumorigenicity 2 pathway inhibitors like itepekimab, tozorakimab, and astegolimab-have demonstrated variable efficacy, often influenced by biomarker profiles and patient characteristics. These findings emphasize the importance of precise patient stratification based on inflammatory endotypes. While biologics mark a significant advancement for select COPD populations, further research is needed to clarify long-term outcomes, refine biomarker thresholds, and broaden treatment options for non-eosinophilic COPD.