Jialing Chen, Caiming Liang, Zhen Wang
In eosinophilic COPD patients, type 2 mAbs reduce moderate-to-severe exacerbations without additional safety signals. Improvements in lung function and quality of life were statistically significant but modest. The symptom benefit was also statistically significant, but should be interpreted with caution given the non-robust sensitivity analysis. This evidence supports the use of type 2 mAbs as an add on treatment for these patients. Future studies should establish a uniform clinical threshold and integrate multiple biomarkers for precision phenotyping.
BACKGROUND: As a heterogeneous disease, chronic obstructive pulmonary disease (COPD) presents with eosinophil driven type 2 inflammation in some patients. Monoclonal antibodies targeting this pathway have shown promising therapeutic effects in related COPD clinical trials, but updated evidence on their efficacy and safety is still needed, specifically in strictly defined eosinophilic COPD patients.
METHODS: This study searched 8 databases from inception to March 17, 2026, for randomized controlled trials (RCTs) comparing type 2 mAbs vs. placebo in eosinophilic COPD, defined as a blood eosinophil count (BEC) ≥300 cells/μL. The primary outcome was the annual rate of moderate-to-severe exacerbations; secondary outcomes covered changes in pre-bronchodilator forced expiratory volume in 1 s (pre-BD FEV1), St. George's Respiratory Questionnaire (SGRQ) score, Evaluating Respiratory Symptoms in COPD (E-RS: COPD) score, and safety-related events. A random effects model in RevMan was used for analysis. Risk of bias was assessed with the RoB 2.0 tool, and the certainty of evidence with the GRADE approach.
RESULTS: 6 RCTs (pooled into 5 research units, as METREX and METREO were combined) involving 3,171 participants were included. Type 2 mAbs reduced the annual rate of moderate-to-severe exacerbations vs. placebo (RR = 0.73, 95% CI 0.66 to 0.80), with consistent subgroup efficacy. Among secondary outcomes, pre-bronchodilator FEV1 improved by 61.97 mL (95% CI 5.09 to 118.85). SGRQ score decreased by -3.16 points (95% CI -4.54 to -1.79). E-RS: COPD score decreased by -0.67 points (95% CI -1.20 to -0.14). There was no statistically significant difference between the treatment group and placebo group in the incidence of adverse events. Evidence certainty was high to moderate, downgraded due to indirectness and inconsistency.
CONCLUSIONS: In eosinophilic COPD patients, type 2 mAbs reduce moderate-to-severe exacerbations without additional safety signals. Improvements in lung function and quality of life were statistically significant but modest. The symptom benefit was also statistically significant, but should be interpreted with caution given the non-robust sensitivity analysis. This evidence supports the use of type 2 mAbs as an add on treatment for these patients. Future studies should establish a uniform clinical threshold and integrate multiple biomarkers for precision phenotyping.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261334527, identifier: CRD420261334527.