Tezepelumab Reduces Exacerbations Across All Seasons in Patients with Severe, Uncontrolled Asthma: A Post Hoc Analysis of the PATHWAY Phase 2b Study
Open Access
- 1 January 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in Journal of Asthma and Allergy
- Vol. ume 14, 1-11
- https://doi.org/10.2147/jaa.s286036
Abstract
Introduction: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), an epithelial cytokine implicated in airway inflammation in asthma, from binding to its heterodimeric receptor. In the PATHWAY phase 2b study, tezepelumab significantly reduced exacerbation rates compared with placebo in adults with severe, uncontrolled asthma, irrespective of baseline disease characteristics. Objective: To evaluate the effect of tezepelumab on asthma exacerbations on a seasonal basis. Methods: This was a post hoc analysis of the PATHWAY study (NCT02054130). Adults (N=550) with severe, uncontrolled asthma 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 annualized asthma exacerbation rate (AAER), total number of days with an exacerbation, proportion of patients with at least one exacerbation or 0, 1 or ≥ 2 exacerbations, and proportion of patients experiencing an exacerbation per day were evaluated by season and over the year, by treatment in the overall study population and in subgroups according to baseline blood eosinophil count (≥ 300 cells/μL or < 300 cells/μL) or atopic asthma status (fluoro-enzyme immunoassay [FEIA]+ or FEIA−). Results: Seasonal variations in exacerbation rates were found, with peaks observed in fall and winter, and greater variations in patients with high blood eosinophil counts (≥ 300 cells/μL). Tezepelumab treatment consistently reduced exacerbation rates across all seasons compared with placebo. Furthermore, there was a trend, which was not significant, toward a reduction in the total number of days with exacerbations and in the proportion of patients with exacerbations during each season in patients treated with tezepelumab compared with those who received placebo, irrespective of blood eosinophil count or atopic asthma status. Conclusion: Tezepelumab reduced exacerbations across all seasons, irrespective of evaluated baseline disease characteristics. These data support the efficacy of tezepelumab in a broad population of patients with severe, uncontrolled asthma.Keywords
This publication has 22 references indexed in Scilit:
- Adherent uncontrolled adult persistent asthma: Characteristics and asthma outcomesThe Journal of Allergy and Clinical Immunology: In Practice, 2015
- The prevalence of severe refractory asthmaJournal of Allergy and Clinical Immunology, 2015
- Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic ResponsesThe New England Journal of Medicine, 2014
- Omalizumab for asthma in adults and childrenEmergencias, 2014
- International ERS/ATS guidelines on definition, evaluation and treatment of severe asthmaEuropean Respiratory Journal, 2013
- Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City ChildrenThe New England Journal of Medicine, 2011
- The development of allergic inflammationNature, 2008
- 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
- Asthma exacerbations {middle dot} 1: EpidemiologyThorax, 2006
- Uncontrolled asthma: A review of the prevalence, disease burden and options for treatmentRespiratory Medicine, 2006