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Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma
We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic (PK) exposure and end points of asthma exacerbation rates (AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV (1)) for patients with severe, uncontroll...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767326/ https://www.ncbi.nlm.nih.gov/pubmed/30661249 http://dx.doi.org/10.1002/cpt.1371 |
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author | Chia, Yen Lin Yan, Li Yu, Binbing Wang, Bing Barker, Peter Goldman, Mitchell Roskos, Lorin |
author_facet | Chia, Yen Lin Yan, Li Yu, Binbing Wang, Bing Barker, Peter Goldman, Mitchell Roskos, Lorin |
author_sort | Chia, Yen Lin |
collection | PubMed |
description | We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic (PK) exposure and end points of asthma exacerbation rates (AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV (1)) for patients with severe, uncontrolled eosinophilic asthma in the SIROCCO/CALIMA phase III trials. In empirical assessment, AER ratios in SIROCCO were similar across PK quartiles. However, the lowest PK quartile in CALIMA had reduced efficacy; low CALIMA placebo AER possibly confounded this result. In population modeling, estimated benralizumab 90% effective concentration for AER reduction was 927 ng/mL, below the Q8W dosage steady‐state average PK concentration (1,066 ng/mL). Benralizumab treatment resulted in more rapid FEV (1) improvement vs. placebo (estimated half‐maximum time: 7.6 vs. 18 days); this response was greater for patients with greater baseline eosinophil counts. These results confirmed 30 mg Q8W is the optimal benralizumab dosage for patients with severe eosinophilic asthma. |
format | Online Article Text |
id | pubmed-6767326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67673262019-10-01 Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma Chia, Yen Lin Yan, Li Yu, Binbing Wang, Bing Barker, Peter Goldman, Mitchell Roskos, Lorin Clin Pharmacol Ther Research We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic (PK) exposure and end points of asthma exacerbation rates (AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second (FEV (1)) for patients with severe, uncontrolled eosinophilic asthma in the SIROCCO/CALIMA phase III trials. In empirical assessment, AER ratios in SIROCCO were similar across PK quartiles. However, the lowest PK quartile in CALIMA had reduced efficacy; low CALIMA placebo AER possibly confounded this result. In population modeling, estimated benralizumab 90% effective concentration for AER reduction was 927 ng/mL, below the Q8W dosage steady‐state average PK concentration (1,066 ng/mL). Benralizumab treatment resulted in more rapid FEV (1) improvement vs. placebo (estimated half‐maximum time: 7.6 vs. 18 days); this response was greater for patients with greater baseline eosinophil counts. These results confirmed 30 mg Q8W is the optimal benralizumab dosage for patients with severe eosinophilic asthma. John Wiley and Sons Inc. 2019-03-22 2019-08 /pmc/articles/PMC6767326/ /pubmed/30661249 http://dx.doi.org/10.1002/cpt.1371 Text en © 2019 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Chia, Yen Lin Yan, Li Yu, Binbing Wang, Bing Barker, Peter Goldman, Mitchell Roskos, Lorin Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma |
title | Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma |
title_full | Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma |
title_fullStr | Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma |
title_full_unstemmed | Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma |
title_short | Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma |
title_sort | relationship between benralizumab exposure and efficacy for patients with severe eosinophilic asthma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767326/ https://www.ncbi.nlm.nih.gov/pubmed/30661249 http://dx.doi.org/10.1002/cpt.1371 |
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