Type 2 inflammation biomarkers and their association with response to dupilumab in COPD (BOREAS): an analysis of a randomised, placebo-controlled, phase 3 trial

BACKGROUND: A raised blood eosinophil count (≥300 cells per μL), a marker of type 2 inflammation, can identify patients with chronic obstructive pulmonary disease (COPD) with higher exacerbation risk. Dupilumab reduced exacerbations in patients with COPD and type 2 inflammation in the BOREAS trial. In this post-hoc analysis, we evaluated the predictive value and longitudinal changes in type 2 inflammatory biomarkers in patients with COPD and type 2 inflammation from the BOREAS trial who received dupilumab treatment. METHODS: BOREAS, a phase 3, multicentre, double-blind, randomised trial was conducted at 275 sites in 24 countries and included patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells per μL). Patients were randomly assigned (1:1) to receive 300 mg of dupilumab every 2 weeks for 52 weeks or matching placebo. Randomisation was stratified by country and inhaled corticosteroid dose at baseline. This post-hoc analysis assessed blood eosinophil counts, fractional exhaled nitric oxide (FeNO), serum eotaxin-3, total plasma immunoglobulin E (IgE), and serum pulmonary and activation-regulated chemokine (PARC) concentrations in the safety population. The study was registered at ClinicalTrials.gov, NCT03930732 and is complete. FINDINGS: BOREAS was conducted between April 15, 2019, and May 2, 2023, and included 939 patients with COPD and type 2 inflammation. 468 patients were randomly assigned to receive 300 mg of dupilumab every 2 weeks for 52 weeks and 471 were randomly assigned to receive matching placebo. 319 (34%) participants were female and 620 (66%) were male. 657 (70%) were former smokers and 282 (30%) were current smokers. At week 52, greater median percentage reductions were observed in dupilumab versus placebo for most biomarkers (total IgE: -22·5% IQR -30·4 to -16·5 vs -0·9% -6·5 to 4·8; FeNO: -28·6% -57·1 to 0 vs -6·9% -35·7 to 25·0; eotaxin-3: -8·8% -15·6 to -2·9 vs -0·4% -5·6 to 5·0; and PARC: -14·4% -29·2 to 2·1 vs -0·8% -13·9 to 17·2). Reductions were similar across treatment groups by blood eosinophil counts. Exacerbation risk overall was reduced, with a greater magnitude of reduction in those with higher baseline blood eosinophil count (p=0·0056) and baseline FeNO (p=0·043). INTERPRETATION: Patients with COPD and type 2 inflammation who were given dupilumab showed reduced type 2 inflammatory biomarkers, with elevated blood eosinophil count and FeNO predicting greater treatment response. These findings support biomarker-driven treatment strategies to optimise therapy. FUNDING: Sanofi and Regeneron Pharmaceuticals.