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Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease

BACKGROUND: High inter‐individual variability in therapeutic response to drugs used in the management of Inflammatory Bowel Disease (IBD) leads to high morbidity and high costs. Genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis and immunogenicity of...

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Autores principales: Bangma, Amber, Voskuil, Michiel D., Uniken Venema, Werna T. C., Brugge, Harm, Hu, Shixian, Lanting, Pauline, Franke, Lude, Dijkstra, Gerard, Festen, Eleonora A. M., Weersma, Rinse K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318341/
https://www.ncbi.nlm.nih.gov/pubmed/32363635
http://dx.doi.org/10.1111/apt.15762
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author Bangma, Amber
Voskuil, Michiel D.
Uniken Venema, Werna T. C.
Brugge, Harm
Hu, Shixian
Lanting, Pauline
Franke, Lude
Dijkstra, Gerard
Festen, Eleonora A. M.
Weersma, Rinse K.
author_facet Bangma, Amber
Voskuil, Michiel D.
Uniken Venema, Werna T. C.
Brugge, Harm
Hu, Shixian
Lanting, Pauline
Franke, Lude
Dijkstra, Gerard
Festen, Eleonora A. M.
Weersma, Rinse K.
author_sort Bangma, Amber
collection PubMed
description BACKGROUND: High inter‐individual variability in therapeutic response to drugs used in the management of Inflammatory Bowel Disease (IBD) leads to high morbidity and high costs. Genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis and immunogenicity of Tumour Necrosis Factor alpha (TNFα) antagonists have been identified, but uptake of pre‐treatment pharmacogenetic testing into clinical guidelines has been slow. AIM: To explore the efficacy of a pharmacogenetic passport for IBD that includes multiple pharmacogenetic predictors of response. METHODS: Patients with IBD exposed to thiopurines and/or TNFα antagonists were retrospectively evaluated for the presence of thiopurine toxicity and/or immunogenicity of TNFα antagonists. All patients were genotyped using both whole‐exome sequencing and the Illumina Global Screening Array. An in‐house‐developed computational pipeline translated genetic data into an IBD pharmacogenetic passport that predicted risks for thiopurine toxicity and immunogenicity of TNFα antagonists per patient. Using pharmacogenetic‐guided treatment guidelines, we calculated clinical efficacy estimates for pharmacogenetic testing for IBD. RESULTS: Among 710 patients with IBD exposed to thiopurines and/or TNFα antagonists, 150 adverse drug responses occurred and our pharmacogenetic passport would have predicted 54 (36%) of these. Using a pharmacogenetic passport for IBD that includes genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis, and immunogenicity of TNFα antagonists, 24 patients need to be genotyped to prevent one of these adverse drug responses. CONCLUSIONS: This study highlights the clinical efficacy of a pharmacogenetic passport for IBD. Implementation of such a pharmacogenetic passport into clinical management of IBD may contribute to a reduction in adverse drug responses.
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spelling pubmed-73183412020-06-29 Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease Bangma, Amber Voskuil, Michiel D. Uniken Venema, Werna T. C. Brugge, Harm Hu, Shixian Lanting, Pauline Franke, Lude Dijkstra, Gerard Festen, Eleonora A. M. Weersma, Rinse K. Aliment Pharmacol Ther Efficacy of a Pharmacogenetic Passport for Inflammatory Bowel Disease BACKGROUND: High inter‐individual variability in therapeutic response to drugs used in the management of Inflammatory Bowel Disease (IBD) leads to high morbidity and high costs. Genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis and immunogenicity of Tumour Necrosis Factor alpha (TNFα) antagonists have been identified, but uptake of pre‐treatment pharmacogenetic testing into clinical guidelines has been slow. AIM: To explore the efficacy of a pharmacogenetic passport for IBD that includes multiple pharmacogenetic predictors of response. METHODS: Patients with IBD exposed to thiopurines and/or TNFα antagonists were retrospectively evaluated for the presence of thiopurine toxicity and/or immunogenicity of TNFα antagonists. All patients were genotyped using both whole‐exome sequencing and the Illumina Global Screening Array. An in‐house‐developed computational pipeline translated genetic data into an IBD pharmacogenetic passport that predicted risks for thiopurine toxicity and immunogenicity of TNFα antagonists per patient. Using pharmacogenetic‐guided treatment guidelines, we calculated clinical efficacy estimates for pharmacogenetic testing for IBD. RESULTS: Among 710 patients with IBD exposed to thiopurines and/or TNFα antagonists, 150 adverse drug responses occurred and our pharmacogenetic passport would have predicted 54 (36%) of these. Using a pharmacogenetic passport for IBD that includes genetic variants predictive of thiopurine‐induced myelosuppression, thiopurine‐induced pancreatitis, and immunogenicity of TNFα antagonists, 24 patients need to be genotyped to prevent one of these adverse drug responses. CONCLUSIONS: This study highlights the clinical efficacy of a pharmacogenetic passport for IBD. Implementation of such a pharmacogenetic passport into clinical management of IBD may contribute to a reduction in adverse drug responses. John Wiley and Sons Inc. 2020-05-03 2020-06 /pmc/articles/PMC7318341/ /pubmed/32363635 http://dx.doi.org/10.1111/apt.15762 Text en © 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Efficacy of a Pharmacogenetic Passport for Inflammatory Bowel Disease
Bangma, Amber
Voskuil, Michiel D.
Uniken Venema, Werna T. C.
Brugge, Harm
Hu, Shixian
Lanting, Pauline
Franke, Lude
Dijkstra, Gerard
Festen, Eleonora A. M.
Weersma, Rinse K.
Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
title Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
title_full Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
title_fullStr Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
title_full_unstemmed Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
title_short Predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
title_sort predicted efficacy of a pharmacogenetic passport for inflammatory bowel disease
topic Efficacy of a Pharmacogenetic Passport for Inflammatory Bowel Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318341/
https://www.ncbi.nlm.nih.gov/pubmed/32363635
http://dx.doi.org/10.1111/apt.15762
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