Dupilumab improves large and small airway spirometry-derived ratios in moderate-to-severe asthma

Purpose: Spirometry-derived ratios are used to distinguish between restrictive and obstructive lung disease, assess airflow through large and small airways, and guide treatment decisions in patients with asthma. Dupilumab, a fully human monoclonal antibody that blocks signaling of IL-4/13, key drivers of type 2 inflammation has been shown to improve lung function in patients with moderate-to-severe asthmaThis study assessed the effect of dupilumab on large (forced expiratory volume in 1 second [FEV 1] / forced vital capacity [FVC]) and small ( forced expiratory flow between 25% and 75% of vital capacity [FEF 25–75% ]/FVC) airway dysfunction using spirometry-derived ratios. Methods: In phase 4 VESTIGE (NCT04400318), adults with type 2 (eosinophils≥300 cells/µL and fractional exhaled nitric oxide [FeNO]≥25 ppb), uncontrolled, moderate-to-severe asthma were randomised to receive add-on dupilumab 300 mg (n=72) or placebo (n=37) every two weeks for 24 weeks. Using a mixed model for repeated measures, we evaluated changes from baseline to Week 24 in four pre-bronchodilator ratios: FEV 1 /FVC and FEF 25–75% /FVC (assessing large and small airway dysfunction, respectively, and expressed as a raw percentage), percent predicted (pp)FEV 1 /ppFVC, and ppFEF 25–75% /ppFVC. Results: Mean baseline values in dupilumab and placebo arms were: FEV 1 /FVC, 60.7% and 61.8%; ppFEV 1 /ppFVC, 76.7% and 77.8%; FEF 25–75% /FVC, 34.0% and 37.8%; and ppFEF 25–75% /ppFVC, 46.2% and 49.5%. At Week 24, dupilumab vs placebo improved FEV 1 /FVC (least sqaure mean difference [95% confidence interval]: 6.8% [3.4, 10.2]; P