Efficacy of Biologics in Patients with Moderate to Very Severe COPD: A Systematic Review.

A growing number of biologics are approved or in development for the treatment of chronic obstructive pulmonary disease (COPD). Many reduce acute exacerbations of COPD (AECOPD), particularly among patients with an elevated blood eosinophil count (BEC). In this systematic review, PubMed and Ovid (MEDLINE and Embase) were searched for phase 2 and 3 randomized controlled trials of biologics in patients with moderate to very severe COPD published between database inception and July 9, 2025. AECOPD rates and changes from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) and St George's Respiratory Questionnaire (SGRQ)/SGRQ for COPD (SGRQ-C) total scores were evaluated for each biologic, overall and by baseline BEC. Sixteen publications were included, covering 12 studies of seven biologics (astegolimab, benralizumab, dupilumab, itepekimab, mepolizumab, tezepelumab and tozorakimab). In overall study populations with no baseline BEC limits, no biologics tested (astegolimab, benralizumab, itepekimab and tezepelumab) reduced AECOPD versus placebo. AECOPD reductions were seen in patients with a baseline BEC ≥300 cells/µL (benralizumab, dupilumab and mepolizumab), BEC <300 cells/µL (astegolimab), and BEC ≥150 cells/µL (mepolizumab and tezepelumab). Only benralizumab and tezepelumab were assessed in patients with a baseline BEC <150 cells/µL; neither reduced AECOPD in this subgroup. Patients with a baseline BEC ≥300 cells/µL (dupilumab and tezepelumab), BEC ≥250 cells/µL (itepekimab) and BEC ≥150 cells/µL (tozorakimab) had improvements in pre-BD FEV1 versus placebo. Improvements in SGRQ total score were observed in patients with BEC ≥300 cells/µL (dupilumab and tezepelumab) and astegolimab improved SGRQ-C total score in patients with BEC >170 cells/µL. Overall, AECOPD reductions and improvements in lung function and health-related quality of life in patients with moderate to very severe COPD varied by biologic and baseline BEC subgroup; within studies, efficacy was generally greater in patients with an elevated baseline BEC, suggesting these patients may benefit most from biologic treatment.