Dupilumab reduces acute exacerbations and improves lung function in patients with COPD with type 2 inflammation irrespective of body mass index, airflow obstruction, dyspnea, and exercise capacity index scores

Respir Med. 2025 May:241:108015. doi: 10.1016/j.rmed.2025.108015. Epub 2025 Feb 28.

Abstract

Background: The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index predicts 5-year mortality risk in chronic obstructive pulmonary disease (COPD); higher scores predict worse outcomes. Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4/13, reduced exacerbations and improved lung function in patients with COPD in the phase 3 BOREAS trial (NCT03930732). We assessed dupilumab efficacy in patients with COPD and type 2 inflammation by baseline BODE index.

Methods: Patients with COPD, moderate-to-severe airflow limitation, screening blood eosinophils ≥300 cells/μL, and high exacerbation risk, on triple therapy, received 300 mg add-on dupilumab or placebo every 2 weeks for 52 weeks. Annualized moderate or severe COPD exacerbation rate and change from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV1) at Weeks 12 and 52 were assessed by baseline BODE index, categorized as low (≤4) or high (>4).

Results: Of 934 patients with reported baseline BODE index scores (dupilumab: 470; placebo: 464), 61.8 % had scores ≤4. Dupilumab reduced exacerbations versus placebo, regardless of baseline BODE index group. Exacerbation reductions were similar by BODE index group; relative risk (95 % confidence interval) for patients with BODE index >4 versus ≤4 was 0.656 (0.496-0.868) versus 0.718 (0.547-0.944). At Weeks 12 and 52, dupilumab consistently improved pre-bronchodilator FEV1 versus placebo, regardless of baseline BODE index group.

Conclusion: Dupilumab reduced exacerbations and improved lung function in patients with COPD and type 2 inflammation irrespective of baseline BODE index score.

Clinical trial registration number: BOREAS trial NCT03930732.

Keywords: BODE index; COPD; Dupilumab; Exacerbations; Lung function; Type 2 inflammation.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Body Mass Index
  • Disease Progression
  • Double-Blind Method
  • Dyspnea / drug therapy
  • Dyspnea / physiopathology
  • Exercise Tolerance / drug effects
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive* / complications
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Respiratory Function Tests
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • dupilumab

Associated data

  • ClinicalTrials.gov/NCT03930732