Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin (TSLP). In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced exacerbations and improved lung function, asthma control and health-related quality of life versus placebo in patients with severe, uncontrolled asthma. This post hoc analysis evaluated the efficacy of tezepelumab in NAVIGATOR patients receiving maintenance treatment meeting step 4 or step 5 of the Global Initiative for Asthma (GINA) guidelines at study entry.

NAVIGATOR was a multicentre, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) receiving medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS; 500 µg/day or > 500 μg/day fluticasone propionate or equivalent, respectively) and at least one additional controller medication with or without oral corticosteroids (OCS) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The annualized asthma exacerbation rate (AAER) over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV₁) and Asthma Control Questionnaire (ACQ)-6 score were assessed in patients receiving MD ICS (−OCS) (GINA 4 subgroup) and those receiving MD ICS (+OCS) or HD ICS (+/−OCS) (GINA 5 subgroup) at study entry.

Overall, 1059 patients received tezepelumab (n = 528) or placebo (n = 531). At study entry, the GINA 4 and 5 subgroups had 252 and 806 patients, respectively. Patients in the GINA 5 subgroup were slightly older and had higher blood eosinophil counts and fractional exhaled nitric oxide levels than those in the GINA 4 subgroup. Among placebo recipients, the AAER over 52 weeks was lower in the GINA 4 subgroup than in the GINA 5 subgroup. Tezepelumab reduced the AAER over 52 weeks versus placebo by 30% (95% CI: −4, 53) and by 61% (95% CI: 51, 68) in the GINA 4 and GINA 5 subgroups, respectively (Figure). At week 52, there were directional improvements in FEV₁ and ACQ-6 score with tezepelumab in both subgroups, both from baseline and versus placebo (Table). 

Tezepelumab reduced exacerbations versus placebo in patients receiving GINA step 4 or step 5 treatment in NAVIGATOR, with similar exacerbation rates observed with tezepelumab in both subgroups. These findings further support the benefits of tezepelumab in a broad population of patients with severe, uncontrolled asthma.