Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2 inflammation. In the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) in patients with uncontrolled, moderate-to-severe asthma, add-on dupilumab 200 mg or 300 mg every 2 weeks reduced exacerbations and improved forced expiratory volume in 1 s (FEV(1)) and quality of life over 52 weeks. This analysis evaluates dupilimab's effect on lung function in the overall population, and subgroups with baseline elevated type 2 inflammatory biomarkers. METHODS: Patients were randomised to 52 weeks of subcutaneous dupilumab 200 mg every 2 weeks, 300 mg every 2 weeks, or matched-volume placebos. Lung function outcomes were analysed in the overall population, in patients with ≥150 eosinophils·µL(−1), ≥300 eosinophils·µL(−1), ≥25 ppb fractional exhaled nitric oxide (F(eNO)), and both ≥150 eosinophils·µL(−1) and ≥25 ppb F(eNO), at baseline. RESULTS: Dupilumab treatment (200 mg and 300 mg every 2 weeks) resulted in significant improvements versus placebo after 52 weeks in pre-bronchodilator FEV(1) (0.20 and 0.13 L, respectively, versus placebo) and post-bronchodilator FEV(1) (0.19 and 0.13 L, respectively), forced vital capacity (FVC) (0.20 and 0.14 L, respectively), forced expiratory flow (0.19 and 0.13 L·s(−1), respectively) and pre-bronchodilator FEV(1)/FVC ratio (1.75% and 1.61%, respectively) in the overall population (p<0.001). Difference versus placebo in post-bronchodilator FEV(1) slope of change (weeks 4–52) was significant (0.04 L·year(−1); p<0.05). Greater improvements were achieved in patients with elevated baseline blood eosinophil and/or F(eNO) levels for most outcomes. CONCLUSIONS: Dupilumab improves lung function outcomes, including large and small airway measurements and fixed airway obstruction, in patients with uncontrolled, moderate-to-severe asthma; particularly in patients with elevated biomarkers of type 2 inflammation.