Relationship between FeNO suppression and Clinical Remission with Tezepelumab in Severe Asthma

<bold>Introduction:</bold> Despite encouraging clinical trial results with the anti-TSLP mAb tezepelumab in severe asthma (SA), the real-world response is unknown. In addition, it remains unknown whether an early reduction in the T2 biomarker FeNO following initiation of treatment may predict clinical response, including the goal of clinical remission. <bold>Methods:</bold> The clinical and biomarker response to tezepelumab in patients with SA completing a minimum of 6 months of treatment at Guy’s SA Centre, UK was assessed. Clinical remission was defined as no exacerbations or requirement for maintenance OCS, ACQ6<1.5 and stable FEV1. FeNO was recorded at baseline, 4 weeks, and 6 months. <bold>Results:</bold> 72 patients (57% female, 61% atopic, 53% child-onset phenotype), including 47 who had switched from another biologic were analysed. Median (IQR) baseline FeNO was 42.5ppb (26-86). Mean (SD) AER fell from 2.9(1.6) at baseline to 1.0(1.97) and 74% of patients remained exacerbation free at 6 months. Mean(SD) ACQ-6 fell from 2.74(1.4) to 1.7(1.5). 26/72 (36%) achieved clinical remission at 6 months. Attainment of clinical remission was associated with a greater reduction in median FeNO at 4 weeks (−23.5ppb vs -9ppb, p=0.02). <bold>Conclusion:</bold> In a real-world cohort of SA patients, tezepelumab led to marked clinical responses in both biologic naïve and biologic switch patients. The magnitude of FeNO suppression at 4 weeks predicted clinical remission at 6 months highlighting FeNO as a potential biomarker of early clinical response.