2022 CSACI annual scientific meeting book of abstracts

Background: Tezepelumab, a human monoclonal antibody, targets thymic stromal lymphopoietin (TSLP).In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma with high or low baseline blood eosinophil counts (BECs) and across all seasons in the overall population.This pre-specified exploratory analysis evaluated the effect of tezepelumab on seasonal asthma exacerbation rates in NAVIGATOR patients grouped by baseline BEC.Methods: NAVIGATOR was a multicentre, 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.The annualized asthma exacerbation rate (AAER) was assessed by season in patients grouped by baseline BEC.Data from patients in the southern hemisphere were transformed to align with northern hemisphere seasons.Results: Of 1059 treated patients, 618 had a BEC of < 300 cells/μL and 441 had a BEC of ≥ 300 cells/μL at baseline.In the placebo group, there were seasonal variations in the AAER, with a peak in winter of 2.32 (95% confidence interval CI: 1.85, 2.91) and 3.07 (95% CI: 2.36, 4.00) in patients with BEC of < 300 cells/µL and ≥ 300 cells/μL, respectively.In patients with a BEC of < 300 cells/μL, tezepelumab reduced the AAER versus placebo by 31% (95% CI: -4, 54) in spring, 37% (95% CI: 5, 58) in summer, 43% (95% CI: 20, 59) in fall and 55% (95% CI: 36, 68) in winter.In patients with a BEC of ≥ 300 cells/μL, tezepelumab reduced the AAER versus placebo by 62% (95% CI: 38, 77) in spring, 80% (95% CI: 67, 88) in summer, 66% (95% CI: 49, 77) in fall and 72% (95% CI: 57, 82) in winter.Conclusions: Tezepelumab reduced exacerbations versus placebo across all seasons in patients with severe, uncontrolled asthma with high or low baseline BECs, consistent with the overall NAVIGATOR population.