Number Needed to Treat with Biologics in Type-2 Inflammation COPD: A Systematic Review and Meta-Analysis

In moderate‑to‑severe chronic obstructive pulmonary disease (COPD), the number needed to treat (NNT) quantifies therapeutic benefit but remains underused for type-2-targeted biologics. This meta-analysis quantified the NNT for type-2-targeted biologics in moderate-to-severe COPD and incorporated the recent evidence on exacerbations, lung function, symptoms, health status, and responder outcomes. We searched PubMed, Embase and Web of Science through July 2025 for phase 2 or 3 RCTs of type-2targeted biologics in adults with COPD. The primary outcome was NNT for moderate-to-severe exacerbations; secondary outcomes included pre-bronchodilator forced expiratory volume in 1 s (FEV₁), St. George's Respiratory Questionnaire (SGRQ), Evaluating Respiratory Symptoms in COPD (E-RS-COPD), and responder proportions. Pooled ratios and mean differences were synthesized using fixed‑ or random‑effects models. Patient-based NNT was derived from cumulative incidence, event‑based NNT was derived from annualized exacerbation rates. Pooled NNTs were estimated under selected baseline‑risk scenarios. Under three baseline‑risk scenarios, pooled patient‑based NNTs for reducing moderate‑to‑severe COPD exacerbations were 12-17 for dupilumab and 11-16 for mepolizumab, benralizumab showed no clear reduction. Event-based NNTs at a baseline annual exacerbation rate of 1.055 per year were 3 for dupilumab and 5 for mepolizumab. Dupilumab was associated with improvements in pre-bronchodilator FEV₁, SGRQ, and E-RS-COPD. For mepolizumab, evidence across these non‑exacerbation outcomes was not consistently observed. In conclusion, pooled patient-based and event-based analyses suggest that both dupilumab and mepolizumab consistently reduce moderate-to-severe exacerbations in eosinophilic or type 2 inflammatory COPD, while improvements in lung function and patient-reported outcomes remain less consistent across biologics and warrant further validation. These findings derive from separate placebo‑controlled trials and should not be interpreted as establishing a comparative efficacy hierarchy among biologics.