Tezepelumab Reduces Exacerbations Across All Seasons in Patients with Severe, Uncontrolled Asthma: A Post Hoc Analysis of the PATHWAY Phase 2b Study
Authors Corren J, Karpefors M, Hellqvist Å, Parnes JR, Colice G
Received 13 October 2020
Accepted for publication 19 December 2020
Published 11 January 2021 Volume 2021:14 Pages 1—11
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Amrita Dosanjh
Jonathan Corren,1 Martin Karpefors,2 Åsa Hellqvist,3 Jane R Parnes,4 Gene Colice5
1Departments of Medicine and Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; 2Data Science and AI, AstraZeneca, Gothenburg, Sweden; 3Biometrics, Late-Stage Development, Respiratory and Immunology, AstraZeneca, Gothenburg, Sweden; 4Amgen, Thousand Oaks, CA, USA; 5Late-Stage Development, Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA
Correspondence: Jonathan Corren
Departments of Medicine and Pediatrics, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA
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: allergens, asthma, eosinophil, seasonal variation, tezepelumab, thymic stromal lymphopoietin