Reimagining COPD treatment: are biologics the next frontier?

Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality with persistent symptom burden and frequent exacerbations despite optimized inhaled therapy. Growing recognition of disease heterogeneity such as a distinct type-2/eosinophilic endotype as well as advances in biologic agents motivate reassessment of monoclonal antibodies (mAbs) as targeted treatments. This narrative review summarizes evidence from Phase 2 and 3 studies for mAbs in COPD, grouping agents by molecular targets (IL-1β, IL-4/IL-4 Rα/IL-13, IL-5/IL-5 Rα, IL-8, IL-17, IL-33/ST2/RAGE/EGFR, TSLP, TNF-α). A literature search of MEDLINE and ClinicalTrials.gov was conducted to identify relevant clinical studies of biologic therapies for COPD, with the search updated through November 2025. Trials of canakinumab, dupilumab, mepolizumab, benralizumab, ABX-IL8, CNTO 6785, astegolimab, itepekimab, tozorakimab, tezepelumab, and earlier neutrophil-directed therapies are reviewed, with emphasis on biomarker-guided enrichment, primary and key secondary outcomes, subgroup signals, and safety profiles. Broad anti-inflammatory approaches have largely failed in unselected COPD populations. By contrast, biologics targeting type-2 inflammation or upstream epithelial alarmins show benefit in biomarker-defined subgroups. Future success depends on precise endotype definition, validated biomarkers, and trials designed for enriched populations; careful risk–benefit assessment and real-world validation are essential before designing future clinical trials.