A comparison of T2 biomarker suppression with Tezepelumab in the real world and phase 3 NAVIGATOR study

<bold>Introduction:</bold> Patients recruited to clinical trials are frequently less severe than those treated in real-world (RW) settings. In the phase 3 NAVIGATOR (NAV) study of the anti-TSLP mAb tezepelumab, only 29.3% of subjects had a baseline FeNO≥50ppb and 15.8% had both a blood eosinophil count (BEC)≥300 cells/mcL and FeNO≥50ppb. Consequently, it remains unclear how effective tezepelumab is at suppressing T2 inflammation in a more severe real-world cohort. <bold>Methods:</bold> T2 biomarker levels at baseline and 6 months post-initiation of tezepelumab were analysed in patients under the care of Guy’s SA centre, UK. These were compared to the biomarker responses from NAV. <bold>Results:</bold> 72 patients (57% female, 61% atopic, 53% child-onset asthma) were analysed. At baseline compared to NAV, 78% vs 60.5% had a FeNO≥25ppb, 43% vs 29.3% had a FeNO≥50ppb and 24% vs 15.8% had a BEC≥300cells/mcL and FeNO≥50ppb. On tezepelumab 23% (RW) vs 11.1% (NAV) still had BEC≥300cells/mcL and 15% (RW) vs 8.4% (NAV) still had FeNO≥50ppb. The proportion with fully suppressed T2 inflammation (BEC<150 and FeNO<25ppb) was 21% (RW) vs 39.1% (NAV) (Figure 1). <bold>Conclusion:</bold> In a RW severe asthma cohort, a large proportion of patients treated with tezepelumab continue to have evidence of T2 inflammation suggesting that other key drivers of IL-5 and IL-13 pathways remain active. The clinical significance requires further assessment. <fig><object-id>erj;64/suppl_68/PA3560/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>