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Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design
The observation of an infusion reaction (IR) in a nonclinical study can cause concern among investigators and regulators in the development of biotherapeutics. Biomarkers can be informative to determine whether the reactions are immune-mediated or test-article related and if there is a potential ris...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893855/ https://www.ncbi.nlm.nih.gov/pubmed/29658009 http://dx.doi.org/10.1016/j.cotox.2017.03.005 |
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author | Mease, Kirsten M. Kimzey, Amy L. Lansita, Janice A. |
author_facet | Mease, Kirsten M. Kimzey, Amy L. Lansita, Janice A. |
author_sort | Mease, Kirsten M. |
collection | PubMed |
description | The observation of an infusion reaction (IR) in a nonclinical study can cause concern among investigators and regulators in the development of biotherapeutics. Biomarkers can be informative to determine whether the reactions are immune-mediated or test-article related and if there is a potential risk to human subjects. IRs encompass a broad range of adverse events with a variety of triggers; the focus of this paper is IRs due to cytokine release syndrome or immune complex formation and the associated biomarkers. Such reactions generally do not preclude clinical development or marketing approval, because it is widely accepted that immune-mediated reactions in nonclinical species are not predictive of human outcomes. Several US approved products (from 2004 to 2016) have documented IRs in nonclinical species. This review article discusses recent examples, the biomarkers evaluated, and implications for study design and conduct. |
format | Online Article Text |
id | pubmed-5893855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier B.V |
record_format | MEDLINE/PubMed |
spelling | pubmed-58938552018-04-11 Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design Mease, Kirsten M. Kimzey, Amy L. Lansita, Janice A. Curr Opin Toxicol Article The observation of an infusion reaction (IR) in a nonclinical study can cause concern among investigators and regulators in the development of biotherapeutics. Biomarkers can be informative to determine whether the reactions are immune-mediated or test-article related and if there is a potential risk to human subjects. IRs encompass a broad range of adverse events with a variety of triggers; the focus of this paper is IRs due to cytokine release syndrome or immune complex formation and the associated biomarkers. Such reactions generally do not preclude clinical development or marketing approval, because it is widely accepted that immune-mediated reactions in nonclinical species are not predictive of human outcomes. Several US approved products (from 2004 to 2016) have documented IRs in nonclinical species. This review article discusses recent examples, the biomarkers evaluated, and implications for study design and conduct. Elsevier B.V 2017-06 /pmc/articles/PMC5893855/ /pubmed/29658009 http://dx.doi.org/10.1016/j.cotox.2017.03.005 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Mease, Kirsten M. Kimzey, Amy L. Lansita, Janice A. Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
title | Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
title_full | Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
title_fullStr | Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
title_full_unstemmed | Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
title_short | Biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
title_sort | biomarkers for nonclinical infusion reactions in marketed biotherapeutics and considerations for study design |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5893855/ https://www.ncbi.nlm.nih.gov/pubmed/29658009 http://dx.doi.org/10.1016/j.cotox.2017.03.005 |
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