BIOLOGICS directed at type 2 inflammation appear to offer the most promising therapeutic option for patients with eosinophilic chronic obstructive pulmonary disease (COPD), according to a multicriteria decision analysis of clinical trials. The evaluation, which examined the strength of evidence across 20 randomized trials, underscores the importance of biomarker stratification in guiding biologic use for COPD management.
Researchers analyzed 12 biologics tested in 9,294 patients and assessed outcomes across four domains: reduction in exacerbations, improvements in lung function, biomarker-guided patient selection, and trial design quality. Dupilumab, an anti–IL-4Rα agent, ranked highest, demonstrating consistent reductions in exacerbation rates and meaningful improvements in FEV1 among patients with eosinophilic COPD. These findings were reinforced by the high quality of supporting trial designs.
Other biologics targeting IL-5 pathways, such as mepolizumab and benralizumab, showed moderate efficacy, but primarily in populations selected for eosinophilic biomarkers. By contrast, anti-alarmin therapies including tozorakimab, itepekimab, astegolimab, and tezepelumab yielded mixed results. While some improvement in lung function was observed, these agents largely failed to achieve significant reductions in exacerbations.
Biologics directed at non–type 2 inflammatory pathways, such as TNF-α, IL-1β, IL-1R1, IL-17A, and IL-8 inhibitors, consistently showed a lack of clinical benefit. Many of these trials were limited by small sample sizes, early-phase designs, and an absence of biomarker-driven stratification.
Overall, the analysis highlights that biologics targeting type 2 inflammation offer the clearest therapeutic advantage in biomarker-selected eosinophilic COPD. In contrast, the current generation of biologics for non-eosinophilic disease has not demonstrated reliable efficacy, emphasizing the critical need for improved patient phenotyping and more targeted intervention strategies in future COPD research.
Reference: Matera MG et al. Multi-Criteria Decision Analysis of Biologics in Chronic Obstructive Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2025;20:3163-3173.
