Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma with and without Nasal Polyposis: A Post Hoc Analysis of the Phase 2b PATHWAY Study
Open Access
- 1 February 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Journal of Asthma and Allergy
- Vol. ume 14, 91-99
- https://doi.org/10.2147/jaa.s288260
Abstract
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.This publication has 36 references indexed in Scilit:
- Omalizumab for asthma in adults and childrenEmergencias, 2014
- Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitisJournal of Allergy and Clinical Immunology, 2013
- The Biology of Thymic Stromal Lymphopoietin (TSLP)Published by Elsevier BV ,2013
- Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthmaJournal of Allergy and Clinical Immunology, 2012
- Association between Severity of Asthma and Degree of Chronic RhinosinusitisAmerican Journal of Rhinology and Allergy, 2011
- Diesel Exhaust Particle-Exposed Human Bronchial Epithelial Cells Induce Dendritic Cell Maturation and Polarization via Thymic Stromal LymphopoietinJournal of Clinical Immunology, 2007
- Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cellsThe Journal of Experimental Medicine, 2007
- Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis: Is the histopathology similar to asthma?Journal of Allergy and Clinical Immunology, 2003
- Human epithelial cells trigger dendritic cell–mediated allergic inflammation by producing TSLPNature Immunology, 2002
- Nasal polyps in asthma and rhinitis: A review of 6,037 patientsJournal of Allergy and Clinical Immunology, 1977