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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...

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Autores principales: Chia, Yen Lin, Yan, Li, Yu, Binbing, Wang, Bing, Barker, Peter, Goldman, Mitchell, Roskos, Lorin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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.
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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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