Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma
Mario Castro, Klaus F. Rabe, Jonathan Corren, Ian Pavord, Constance H. Katelaris, Yuji Tohda, Bingzhi Zhang, Megan S. Rice, Jaman Maroni, Paul Rowe, Gianluca Pirozzi, Nikhil Amin, Marcella Ruddy, Bolanle Akinlade, Neil M.H. Graham, Ariel Teper
Abstract
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.