Impact of Dupilumab on Type 2 Inflammatory Biomarkers in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Abstract RATIONALE: Up to 40% of patients with COPD have type 2 inflammation, indicated by elevated blood eosinophil counts. Dupilumab, a monoclonal antibody, blocks interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation. In the BOREAS and NOTUS trials, dupilumab significantly reduced moderate or severe exacerbations and improved lung function in patients with COPD and type 2 inflammation. Safety was generally consistent with the known dupilumab safety profile. This post hoc analysis of pooled data assessed the impact of dupilumab on type 2 biomarkers in patients with COPD and type 2 inflammation. METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), both phase 3, randomized, placebo-controlled trials, enrolled 1,874 patients (aged 40 to 85 years) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (blood eosinophil count ≥300 cells/L at screening). Patients were treated with dupilumab 300 mg (n = 938) or placebo (n = 936) every 2 weeks. Endpoints assessed included change from baseline to Week 52 in blood eosinophil count, fractional exhaled nitric oxide (FeNO), and IgE levels in the intention-to-treat population. All data are shown as median (Q1 to Q3). RESULTS: Baseline blood eosinophil counts were 340.0 (240.0 to 460.0) cells/μL for patients receiving dupilumab and 330.0 (230.0 to 460.0) for those on placebo. By Week 52, similar median change from baseline in blood eosinophil count was observed in the dupilumab group (−40 [-160 to 80] cells/μL [14% decrease]) and in the placebo group (-40 [-140 to 50] cells/µL [11% decrease]). Patients receiving dupilumab had baseline FeNO of 17.0 (10.0 to 29.0) ppb and those on placebo 16.0 (10.0 to 30.0) ppb. By Week 52, median change from baseline in FeNO was -3 (-13 to 10) ppb (23.3% decrease) in the dupilumab group and 0 (-7 to 4) ppb (no change) in the placebo group. Baseline IgE levels were 126.5 (46.1 to 423.0) IU/mL for patients on dupilumab and 123.0 (40.2 to 347.0) for those on placebo. Median change from baseline to Week 52 in IgE levels in dupilumab recipients was -77 (-255 to -20) IU/mL (65% decrease) and in placebo was -2 (-39 to 21) IU/mL (4% decrease). CONCLUSIONS: Overall, treatment with dupilumab resulted in reductions in type 2 inflammatory biomarkers, including serum IgE and FeNO levels over time; blood eosinophil counts remained stable, consistent with the known mechanism of action of dupilumab.