S31 Dupilumab reduces severe exacerbations across baseline disease characteristics in patients with elevated baseline type 2 biomarkers: the LIBERTY ASTHMA QUEST study

Introduction Dupilumab, a fully human VelocImmune®-derived monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation in multiple diseases. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks (q2w) vs placebo reduced severe exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated type 2 biomarkers at baseline. This post hoc analysis assessed dupilumab effect on severe asthma exacerbation rates by baseline disease characteristics in patients with baseline blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥20 ppb. Methods Annualized severe exacerbation rates during the 52-week treatment period were assessed using negative binomial regression models. Results Dupilumab 200 mg/300 mg q2w vs placebo reduced the annualized rate of severe exacerbations during the 52-week treatment period in all subgroups of patients defined by controller medications at randomization, pre-bronchodilator FEV1 (≤1.75 L/>1.75 L), number of severe asthma exacerbations (≥1, ≥2, ≥3) in the previous year, smoking history (never smoked/former smoker), and age at asthma onset (≤40 years/>40 years) (figure 1). The effect of dupilumab was significant in all subgroups except for 2 subgroups with relatively fewer patients. Overall, the most frequent dupilumab 200 mg/300 mg vs matched placebo adverse event was injection-site reaction (15%/18% vs 5%/10%). Conclusions Dupilumab significantly reduced severe exacerbations across most baseline disease characteristics in patients with uncontrolled, moderate-to-severe asthma with evidence of type 2 inflammation at baseline. Dupilumab was generally well tolerated.