Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study
Andrew Menzies‐Gow, Christopher S. Ambrose, Gene Colice, Gillian Hunter, Bill Cook, Néstor A. Molfino, Jean‐Pierre Llanos, Elliot Israel
Abstract
Severe asthma is associated with airway inflammation and airway obstruction. In the phase 3 NAVIGATOR study, tezepelumab treatment significantly improved pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the effect of tezepelumab versus placebo on additional lung function parameters in patients from NAVIGATOR. NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) receiving medium- or high-dose inhaled corticosteroids and at least one additional controller medication, with or without oral corticosteroids, were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline to week 52 in pre-bronchodilator FEV 1 , post-bronchodilator FEV 1 , forced vital capacity (FVC), pre-bronchodilator FEV 1 /FVC ratio, pre-bronchodilator forced expiratory flow between 25 and 75% of vital capacity (FEF 25–75 ), and morning and evening peak expiratory flow (PEF) were assessed. Tezepelumab treatment improved all evaluated lung function parameters over 52 weeks compared with placebo [least-squares mean difference (95% confidence interval): pre-bronchodilator FEV 1 , 0.13 (0.08, 0.18) L; post-bronchodilator FEV 1 , 0.12 (0.07, 0.16) L; FVC, 0.13 (0.07, 0.19) L; FEV 1 /FVC ratio, 2.06% (1.22%, 2.90%); FEF 25–75 , 0.13 (0.07, 0.19) L/s; morning PEF, 16.6 (8.1, 25.1) L/min; and evening PEF, 14.9 (6.3, 23.4) L/min]. Improvements were observed as early as weeks 1–2 and were maintained over 52 weeks. Greater improvements in lung function compared with placebo were observed in patients with a disease duration of less than 20 years, those with baseline post-bronchodilator FEV 1 reversibility of at least 20%, and in patients with a baseline post-bronchodilator FEV 1 /FVC ratio of less than 0.7. These findings further support the benefits of tezepelumab treatment in improving airflow limitation in patients with severe, uncontrolled asthma. NAVIGATOR (NCT03347279).