Biologic therapies targeting type 2 inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomised controlled trials.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and a subset of patients exhibits type 2 (T2) inflammation. Biologic therapies targeting T2 inflammatory pathways have been evaluated in COPD, but their clinical efficacy remains variable. We performed a systematic review and meta-analysis to assess the efficacy and safety of biologic therapies targeting T2 inflammation in COPD.

Methods: Randomised controlled trials evaluating biologic therapies targeting interleukin (IL)-5, IL-5 receptor α, IL-4/IL-13 or thymic stromal lymphopoietin in patients with COPD and biomarker-defined T2 inflammation were systematically identified. Outcomes included moderate or severe COPD exacerbations, lung function (forced expiratory volume in 1 s (FEV₁)), health-related quality of life assessed by the St George's Respiratory Questionnaire (SGRQ) and serious adverse events. Random-effects meta-analyses were conducted when at least two comparable studies were available. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool.

Results: Seven randomised controlled trials were included in the quantitative synthesis. Biologic therapies targeting T2 inflammation significantly reduced the rate of moderate or severe COPD exacerbations compared with placebo (rate ratio 0.77, 95% CI 0.72 to 0.83; p<0.001; I²=0%). Lung function improved modestly with a pooled increase in FEV₁ of 43 mL (95% CI 12.5 to 73.6; p=0.006; I²=55.3%). SGRQ total scores improved by -2.46 units (95% CI -3.43 to -1.49; p<0.001; I²=0%). Subgroup analyses showed the greatest reduction in exacerbations with IL-4/IL-13-targeting therapy in patients with blood eosinophil counts ≥300 cells/µL. No significant increase in serious adverse events was observed.

Conclusions: Biologic therapies targeting T2 inflammation improve clinical outcomes in certain patients with COPD. The most consistent improvements were observed in studies that focused on inhibiting the IL-4/IL-13 pathway. However, variations in patient selection and in T2 enrichment strategies across trials make direct comparisons challenging. These results favour a biomarker-based, personalised approach over the routine use of biologics in unselected populations with COPD.