Dupilumab Is Effective in Patients With Moderate-to-Severe Uncontrolled GINA-Defined Type 2 Asthma Irrespective of an Allergic Asthma Phenotype.

Abstract

The Global Initiative for Asthma report recommends consideration of add-on biologics for patients with type 2 inflammation (blood eosinophils ≥150 cells/μL, fractional exhaled nitric oxide [Feno] ≥20 parts per billion or allergic asthma) whose asthma cannot be controlled by high-dose inhaled corticosteroids. In QUEST (NCT02414854), add-on dupilumab versus placebo was efficacious in patients with uncontrolled, moderate to severe asthma, including those with eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 25 parts per billion. To assess dupilumab efficacy in patients with a type 2 phenotype in the presence or absence of allergic asthma phenotype. Patients aged 12 years or older received add-on dupilumab 200/300 mg versus matched placebo every 2 weeks for 52 weeks. Allergic asthma phenotype was defined as baseline serum total IgE greater than or equal to 30 IU/mL and 1 or more perennial aeroallergen-specific IgE level greater than or equal to 0.35 kU/L. Annualized rate of severe asthma exacerbations and changes from study baseline in prebronchodilator and postbronchodilator FEV₁ were evaluated in patients with allergic and nonallergic phenotype with baseline blood eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 20 parts per billion. Of 1902 patients in QUEST, 83.3% had eosinophils and/or Feno above Global Initiative for Asthma thresholds; 56.9% had evidence for allergic asthma. Dupilumab significantly reduced the rate of severe asthma exacerbations in patients with (48.8%) and without (64.0%) evidence of allergic asthma and improved prebronchodilator and postbronchodilator FEV₁ in patients with elevated type 2 biomarkers, irrespective of whether they showed evidence of an allergic asthma phenotype. In patients with type 2 biomarkers over Global Initiative for Asthma thresholds, dupilumab significantly reduced exacerbations and improved lung function. Efficacy was not impacted by allergic status.