Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study.

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 1s (FEV1) 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 (12-80years 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 210mg or placebo subcutaneously every 4weeks for 52weeks. Changes from baseline to week 52 in pre-bronchodilator FEV1, post-bronchodilator FEV1, forced vital capacity (FVC), pre-bronchodilator FEV1/FVC ratio, pre-bronchodilator forced expiratory flow between 25 and 75% of vital capacity (FEF25-75), and morning and evening peak expiratory flow (PEF) were assessed. Tezepelumab treatment improved all evaluated lung function parameters over 52weeks compared with placebo [least-squares mean difference (95% confidence interval): pre-bronchodilator FEV1, 0.13 (0.08, 0.18) L; post-bronchodilator FEV1, 0.12 (0.07, 0.16) L; FVC, 0.13 (0.07, 0.19) L; FEV1/FVC ratio, 2.06% (1.22%, 2.90%); FEF25-75, 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 52weeks. Greater improvements in lung function compared with placebo were observed in patients with a disease duration of less than 20years, those with baseline post-bronchodilator FEV1 reversibility of at least 20%, and in patients with a baseline post-bronchodilator FEV1/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).