Claire Emson,1 Jonathan Corren,2 Kinga Saapa,3 sa Hellqvist,4 Jane R Parnes,5 Gene Colice6

1Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA; 2David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; 3Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland; 4Biometrics, Late-Stage Development, Respiratory and Immunology, AstraZeneca, Gothenburg, Sweden; 5Amgen, Thousand Oaks, CA, USA; 6Late-Stage Development Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA

Correspondence: Claire EmsonAstraZeneca, One MedImmune Way, Gaithersburg, MD, 20878, USATel +13013980304Email Claire.emson@astrazeneca.com

Background: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis, from binding to its heterodimeric receptor. In the phase 2b PATHWAY study, tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control, in adults with severe, uncontrolled asthma. This post hoc analysis assessed the efficacy of tezepelumab in adults with severe, uncontrolled asthma with and without nasal polyposis (NP).Methods: In this post hoc analysis of the PATHWAY study (NCT02054130), participants (N=550) were randomized 1:1:1:1 to receive subcutaneous tezepelumab 70 mg every 4 weeks (Q4W), 210 mg Q4W or 280 mg every 2 weeks (Q2W), or placebo Q2W, for 52 weeks. The AAER over 52 weeks and the change from baseline to week 52 in blood eosinophil count, fractional exhaled nitric oxide (FeNO) levels and serum levels of interleukin (IL)-5 and IL-13 with tezepelumab 210 mg (the phase 3 dose) and placebo were analyzed in patients grouped by self-reported presence (NP+) or absence (NP) of NP at screening.Results: At baseline, NP+ patients had higher blood eosinophil counts, higher FeNO levels and higher serum IL-5 and IL-13 levels than NP patients. Tezepelumab 210 mg reduced the AAER versus placebo to a similar extent in both NP+ and NP patients (NP+, 75% [95% confidence interval (CI): 15, 93], n=23; NP, 73% [95% CI: 47, 86], n=112). Patients treated with tezepelumab 210 mg demonstrated greater reductions in blood eosinophil count and levels of FeNO, IL-5 and IL-13 than placebo-treated patients, irrespective of NP status.Discussion: Tezepelumab reduced exacerbations and reduced type 2 inflammatory biomarkers in patients with and those without NP, supporting its efficacy in a broad population of patients with severe asthma.

Keywords: asthma, biomarkers, nasal polyps, sinusitis, tezepelumab, thymic stromal lymphopoietin

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Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma w | JAA - Dove Medical Press