EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA AND HIGH BASELINE BLOOD EOSINOPHIL COUNTS

Abstract

<h3>Introduction</h3> The efficacy of biologics for severe asthma is greater in patients with higher blood eosinophil counts (BECs) than those with lower BECs. Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma, irrespective of baseline BECs. This exploratory analysis assessed the efficacy of tezepelumab in patients with high baseline BECs (≥ 500 cells/μL) in NAVIGATOR. <h3>Methods</h3> NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. At week 52, AAER and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV₁) were assessed by baseline BEC (≥ 500, ≥ 750 and ≥ 1000 cells/μL). <h3>Results</h3> Of 1059 patients, 209 had BECs ≥ 500 cells/μL, 76 had BECs ≥ 750 cells/μL and 33 had BECs ≥ 1000 cells/μL at baseline. Among placebo recipients, AAERs increased with increasing BEC. Tezepelumab reduced the AAER versus placebo by 74–77% across these BEC subgroups (<b>Figure</b>). Tezepelumab improved pre-BD FEV₁: least squares mean differences versus placebo were 0.26 L (95% confidence interval [CI]: 0.15–0.37), 0.21 L (95% CI: 0.02–0.40) and 0.41 L (95% CI: 0.13–0.69) in patients with baseline BECs ≥ 500, ≥ 750 and ≥ 1000 cells/μL, respectively. <h3>Conclusion</h3> Tezepelumab substantially reduced exacerbations and improved lung function versus placebo in patients with severe, uncontrolled asthma across all subgroups with high baseline BECs.