EFFECT OF TEZEPELUMAB ON ASTHMA INFLAMMATORY BIOMARKER LEVELS VARIES BY BASELINE BIOMARKER LEVELS

Abstract

<h3>Introduction</h3> In the phase 3 NAVIGATOR study, tezepelumab reduced exacerbations irrespective of baseline biomarkers, and substantially reduced levels of inflammatory biomarkers (blood eosinophil count [BEC], fractional exhaled nitric oxide [FeNO], and serum total immunoglobulin E [IgE]) in patients with severe, uncontrolled asthma. This <i>post hoc</i> analysis assessed the effect of tezepelumab on biomarker levels in patients grouped by baseline biomarker levels. <h3>Methods</h3> NAVIGATOR (NCT03347279) 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. Changes from baseline to week 52 in BEC, FeNO levels and serum total IgE levels were assessed in patients grouped by baseline levels of the respective biomarker. <h3>Results</h3> Overall, 1059 patients received either tezepelumab (n=528) or placebo (n=531). At week 52, tezepelumab reduced BEC, FeNO levels and serum total IgE levels in those with elevated biomarkers at baseline (<b>Figure</b>). Mean relative reductions from baseline with tezepelumab were generally greater in those with higher baseline biomarker levels versus those with lower baseline biomarker levels. For the lowest baseline BEC and FeNO level subgroups, small decreases from baseline were observed with tezepelumab, while placebo recipients demonstrated an increase from baseline at week 52. <h3>Conclusion</h3> Tezepelumab reduced levels of all key inflammatory biomarkers in patients with severe, uncontrolled asthma, with greater reductions in patients with higher baseline levels of the respective biomarker. These data further support the anti-inflammatory effects of tezepelumab in patients with severe asthma.