ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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Oral Corticosteroid-Sparing Effect of Tezepelumab in Adults with Severe Asthma
Session Title
D7 - D007 ADVANCES IN ASTHMA THERAPIES
Abstract
A1197 - Oral Corticosteroid-Sparing Effect of Tezepelumab in Adults with Severe Asthma
Author Block: M. Wechsler1, A. Menzies Gow2, C. E. Brightling3, P. Kuna4, S. Korn5, T. Welte6, J. M. Griffiths7, K. Sałapa8, Å. Hellqvist9, G. Almqvist10, P. Kaur11, T. Skärby10, G. Colice12; 1National Jewish Health, Denver, CO, United States, 2Royal Brompton Hospital, London, United Kingdom, 3NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 4Department of Internal Medicine, Asthma and Allergy, Medical University of Łódź, Łódź, Poland, 5Pulmonary Department, Mainz University Hospital, Mainz, Germany, 6Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany, 7Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, United States, 8Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland, 9Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 10Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 11Global Development, Amgen, Thousand Oaks, CA, United States, 12Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
RATIONALE
Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in asthma pathogenesis. SOURCE evaluated the oral corticosteroid (OCS)-sparing effects of tezepelumab in adults with severe, OCS-dependent asthma.
METHODS
SOURCE was a phase 3, multicenter, randomized, double-blind, placebo-controlled study (NCT03406078). After an OCS optimization period of ≤8 weeks, patients (18-80 years old) were randomized 1:1 to receive tezepelumab 210 mg subcutaneously or placebo every 4 weeks for 48 weeks (comprising a 4-week induction phase, a 36-week OCS reduction phase and an 8-week maintenance phase). The primary endpoint was the categorized percentage reduction from baseline in maintenance daily OCS dose at week 48, while not losing asthma control. This was also evaluated in patients grouped by baseline blood eosinophil count (<300 or ≥300 cells/µL and <150 or ≥150 cells/µL). The key secondary endpoint was the annualized asthma exacerbation rate (AAER) over 48 weeks. An additional secondary endpoint was the change from baseline to week 48 in pre-bronchodilator forced expiratory volume in 1 second (FEV1).
RESULTS
Overall, 150 patients were randomized (tezepelumab 210 mg, n=74; placebo, n=76). The (cumulative) odds of achieving a category of greater percentage reduction in maintenance OCS dose at week 48 were numerically higher with tezepelumab than placebo (odds ratio 1.28, 95% CI: 0.69, 2.35; p=0.43). Tezepelumab numerically reduced the AAER versus placebo over 48 weeks by 31% (95% CI: -9, 56; p=0.11). Compared with placebo, tezepelumab improved pre-bronchodilator FEV1 by 0.26 L (95% CI: 0.13, 0.39), despite reductions in maintenance OCS dose. Improvements in FEV1 occurred as early as the first post-baseline measurement time point (week 4) and were sustained throughout the treatment period. In patients with a baseline blood eosinophil count ≥150 cells/µL and ≥300 cells/µL, the (cumulative) odds of achieving a category of greater percentage reduction in maintenance OCS dose at week 48 were 2.58 (95% CI: 1.16, 5.75) and 3.49 (95% CI: 1.16, 10.49) times higher with tezepelumab than placebo, respectively (Figure). No effects of tezepelumab versus placebo on OCS dose reduction were observed in patients with low baseline blood eosinophil counts (<300 cells/µL and <150 cells/µL).
CONCLUSIONS
Tezepelumab reduced OCS use in patients with OCS-dependent asthma, but statistical significance versus placebo was not achieved. Improvements in pre-bronchodilator FEV1 were observed despite reductions in OCS use. Tezepelumab increased the odds of a reduction in OCS use versus placebo in patients with high baseline blood eosinophil counts.
Author Block: M. Wechsler1, A. Menzies Gow2, C. E. Brightling3, P. Kuna4, S. Korn5, T. Welte6, J. M. Griffiths7, K. Sałapa8, Å. Hellqvist9, G. Almqvist10, P. Kaur11, T. Skärby10, G. Colice12; 1National Jewish Health, Denver, CO, United States, 2Royal Brompton Hospital, London, United Kingdom, 3NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, United Kingdom, 4Department of Internal Medicine, Asthma and Allergy, Medical University of Łódź, Łódź, Poland, 5Pulmonary Department, Mainz University Hospital, Mainz, Germany, 6Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany, 7Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, United States, 8Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland, 9Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 10Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, 11Global Development, Amgen, Thousand Oaks, CA, United States, 12Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
RATIONALE
Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, an epithelial-derived cytokine implicated in asthma pathogenesis. SOURCE evaluated the oral corticosteroid (OCS)-sparing effects of tezepelumab in adults with severe, OCS-dependent asthma.
METHODS
SOURCE was a phase 3, multicenter, randomized, double-blind, placebo-controlled study (NCT03406078). After an OCS optimization period of ≤8 weeks, patients (18-80 years old) were randomized 1:1 to receive tezepelumab 210 mg subcutaneously or placebo every 4 weeks for 48 weeks (comprising a 4-week induction phase, a 36-week OCS reduction phase and an 8-week maintenance phase). The primary endpoint was the categorized percentage reduction from baseline in maintenance daily OCS dose at week 48, while not losing asthma control. This was also evaluated in patients grouped by baseline blood eosinophil count (<300 or ≥300 cells/µL and <150 or ≥150 cells/µL). The key secondary endpoint was the annualized asthma exacerbation rate (AAER) over 48 weeks. An additional secondary endpoint was the change from baseline to week 48 in pre-bronchodilator forced expiratory volume in 1 second (FEV1).
RESULTS
Overall, 150 patients were randomized (tezepelumab 210 mg, n=74; placebo, n=76). The (cumulative) odds of achieving a category of greater percentage reduction in maintenance OCS dose at week 48 were numerically higher with tezepelumab than placebo (odds ratio 1.28, 95% CI: 0.69, 2.35; p=0.43). Tezepelumab numerically reduced the AAER versus placebo over 48 weeks by 31% (95% CI: -9, 56; p=0.11). Compared with placebo, tezepelumab improved pre-bronchodilator FEV1 by 0.26 L (95% CI: 0.13, 0.39), despite reductions in maintenance OCS dose. Improvements in FEV1 occurred as early as the first post-baseline measurement time point (week 4) and were sustained throughout the treatment period. In patients with a baseline blood eosinophil count ≥150 cells/µL and ≥300 cells/µL, the (cumulative) odds of achieving a category of greater percentage reduction in maintenance OCS dose at week 48 were 2.58 (95% CI: 1.16, 5.75) and 3.49 (95% CI: 1.16, 10.49) times higher with tezepelumab than placebo, respectively (Figure). No effects of tezepelumab versus placebo on OCS dose reduction were observed in patients with low baseline blood eosinophil counts (<300 cells/µL and <150 cells/µL).
CONCLUSIONS
Tezepelumab reduced OCS use in patients with OCS-dependent asthma, but statistical significance versus placebo was not achieved. Improvements in pre-bronchodilator FEV1 were observed despite reductions in OCS use. Tezepelumab increased the odds of a reduction in OCS use versus placebo in patients with high baseline blood eosinophil counts.
