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Dupilumab Efficacy in Patients with Type 2 Asthma with and without Elevated Blood Neutrophils
Eugene R Bleecker1, Reynold A Panettieri2, Njira L Lugogo3
1University of Arizona, College of Medicine, Division of Genomics and Precision Medicine, Department of Medicine, 1230 North Cherry Street, Suite 251, Tucson, AZ 85721, USA.
Introduction:
Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts.
Methods:
Annualized severe exacerbation rates during the 52-week treatment period and least-squares mean change from baseline in FEV1 over time were evaluated for patients with elevated type 2 biomarkers at baseline (blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 ppb; and eosinophils ≥ 300 cells/µL or FeNO ≥ 50 ppb) and low (<4,000 cells/µL) or high (≥4,000 cells/µL) neutrophil counts.
Results:
Dupilumab significantly reduced annualized severe exacerbation rates compared with placebo during the 52-week treatment period in patients with elevated type 2 biomarkers, irrespective of baseline neutrophil count (P < 0.0001 for all comparisons). Significant improvements in FEV1 versus placebo were observed as early as Week 2 and over the 52-week treatment period, irrespective of baseline neutrophil count (P < 0.001 for all comparisons). Safety findings were similar across all subgroups, regardless of neutrophil counts at baseline.
Conclusions:
Dupilumab treatment significantly reduced annualized severe exacerbation rates and improved lung function in patients with uncontrolled, moderate-to-severe, type 2 asthma, irrespective of baseline blood neutrophil count. This trial is registered with NCT02414854.
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