Type 2 Inflammatory Biomarkers and Lung function Improvement in Patients with Chronic Obstructive Pulmonary Disease (COPD) Receiving Placebo Therapy

Rationale: Type 2 inflammation in chronic obstructive pulmonary disease (COPD) is characterized by elevated blood eosinophil counts. In BOREAS and NOTUS, add-on dupilumab vs placebo reduced exacerbation rates and improved lung function in patients with COPD and type 2 inflammation. Safety was consistent with the known dupilumab safety profile. This post hoc analysis of pooled data from BOREAS and NOTUS assessed the predictive value of blood eosinophil counts and FeNO on lung function in patients who received placebo. Methods: BOREAS (NCT03930732) and NOTUS (NCT04456673), both Phase 3, randomized, placebo-controlled trials, enrolled 1,874 patients aged 40–85 years with COPD with moderate-to-severe airflow limitation and type 2 inflammation (screening blood eosinophil counts≥300 cells/µL). Patients were randomized to dupilumab 300 mg or placebo every second week for 52 weeks. Regression analyses were conducted to investigate change in pre-bronchodilator forced expiratory volume in 1 second (FEV 1 ) from baseline to Week 52 according to blood eosinophil counts and FeNO levels in patients with available data (N=865; subgroup 1), including former (N=654; subgroup 2) and current smokers (N=282; subgroup 3). Baseline biomarkers were log-transformed; post-bronchodilator FEV 1 is reported as ( r ) ( P -value) for lung function as well as least square [LS] mean change from baseline to Week 52. Results : Univariate regression analysis showed weak correlations between baseline blood eosinophil counts and worsening lung function in patients from subgroup 1 ( r =0.029; P =0.298), subgroup 2 ( r =0.035; P =0.270), and subgroup 3 ( r =−0.012; P =0.782). We also observed weak correlations between baseline FeNO levels and worsening lung function in patients from subgroup 1 ( r =0.094; P