Stability of Blood Eosinophil Counts in Patients With Chronic Obstructive Pulmonary Disease (COPD) and Type 2 Inflammation in the BOREAS and NOTUS Trials

Abstract RATIONALE: A subset of patients with COPD have elevated blood eosinophil counts (BEC), a marker for type 2 (T2) inflammation. Dupilumab blocks interleukin-4 and 13, central drivers of T2 inflammation. In BOREAS and NOTUS, dupilumab reduced exacerbations and improved lung function in patients with COPD and T2 inflammation. This post-hoc analysis assesses BEC stability over time in data pooled from BOREAS and NOTUS. METHODS: BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, placebo-controlled trials, randomized 1,874 patients (40-85 years) with COPD, moderate-to-severe airflow limitation, and screening BEC ≥300 cells/µL to dupilumab 300mg (n=938) or placebo (n=936) q2w for 52 weeks. BEC were measured at screening, baseline (treatment day 1), and Weeks 4, 8, 12, 24, 36, 52, and 64. Proportions of patients with BEC <150, 150 to <300, and ≥300 cells/µL and BEC change from screening over the 52-week treatment period and 12-week follow were assessed. RESULTS: Median baseline BEC (Q1, Q3) were 340.0 (240.0, 460.0) and 330.0 (230.0, 460.0) cells/μL in the dupilumab and placebo arms, respectively. Median BEC were reduced by -10.0 (- 130.0, 110.0) and – 20.0 (- 120.0, 70.0) cells/μL at Week 12; by -30.0 (-140.0, 90.0) and -20.0 (-130.0, 80.0) cells/μL at Week 24; by -40.0 (-160.0, 80.0) and-40.0 (-140.0, 50.0) cells/µL at Week 52; and by -50.0 (-160.0, 40.0) and -30.0 (-140.0, 60.0) cells/μL after the 12-week follow-up period, for dupilumab and placebo, respectively. The proportion of patients with BEC <150, 150 to <300, and ≥300 cells/μL were 8.8%, 30.1%, and 61.2% (dupilumab) and 9.4%, 30.6%, and 60.0% (placebo) at baseline; 16.2%, 40.2%, 43.6% (dupilumab) and 15.2%, 35.4%, 49.3% (placebo) at Week 52; and 17.3%, 36.1%, 46.7% (dupilumab) and 13.4%, 37.7%, 48.9% (placebo) in the 12-week follow-up period (Figure). Approximately 62% of all participants had an BEC ≥150 at all visit times and approximately 20% of all participants were above 300 at all visit times (excluding screening). After 64 weeks, around 50% of patients had a BEC of ≥300 cells/mL in both dupilumab and placebo groups. Safety was consistent with the known dupilumab profile. CONCLUSIONS: For patients in BOREAS and NOTUS, BEC remained largely stable and elevated over the treatment and follow-up periods. Some variability in BEC may exist, and a review of BEC over time may be appropriate to identify patients with T2 inflammation.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.