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TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned

Variants in thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and...

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Autores principales: Goh, Liuh Ling, Lim, Chia Wei, Leong, Khai Pang, Ong, Kiat Hoe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537458/
https://www.ncbi.nlm.nih.gov/pubmed/36210828
http://dx.doi.org/10.3389/fphar.2022.837164
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author Goh, Liuh Ling
Lim, Chia Wei
Leong, Khai Pang
Ong, Kiat Hoe
author_facet Goh, Liuh Ling
Lim, Chia Wei
Leong, Khai Pang
Ong, Kiat Hoe
author_sort Goh, Liuh Ling
collection PubMed
description Variants in thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing. The test was most commonly ordered for Gastroenterology (40.0%) and Neurology (31.4%), with an average turnaround time of 2 days. Following testing, 24.3% patients were identified as intermediate or poor metabolizers, resulting in 51 recommendations for a drug or dose change in thiopurine therapy, which were implemented in 28 (54.9%) patients. In the remaining patients, 14 were not adjusted and 9 had no data available. Focusing on drug gene interactions available for testing in our laboratory, multi-gene PGx results would present opportunities for treatment optimization for at least 33.8% of these patients who were on 2 or more concurrent medications with actionable PGx guidance. However, the use of PGx panel testing in clinical practice will require the development of guidelines and education as revealed by a survey with the test providers. The evaluation demonstrated successful implementation of single gene PGx testing and this experience guides the transition to a pre-emptive multi-gene testing approach that provides the opportunity to improve clinical care.
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spelling pubmed-95374582022-10-08 TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned Goh, Liuh Ling Lim, Chia Wei Leong, Khai Pang Ong, Kiat Hoe Front Pharmacol Pharmacology Variants in thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing. The test was most commonly ordered for Gastroenterology (40.0%) and Neurology (31.4%), with an average turnaround time of 2 days. Following testing, 24.3% patients were identified as intermediate or poor metabolizers, resulting in 51 recommendations for a drug or dose change in thiopurine therapy, which were implemented in 28 (54.9%) patients. In the remaining patients, 14 were not adjusted and 9 had no data available. Focusing on drug gene interactions available for testing in our laboratory, multi-gene PGx results would present opportunities for treatment optimization for at least 33.8% of these patients who were on 2 or more concurrent medications with actionable PGx guidance. However, the use of PGx panel testing in clinical practice will require the development of guidelines and education as revealed by a survey with the test providers. The evaluation demonstrated successful implementation of single gene PGx testing and this experience guides the transition to a pre-emptive multi-gene testing approach that provides the opportunity to improve clinical care. Frontiers Media S.A. 2022-09-23 /pmc/articles/PMC9537458/ /pubmed/36210828 http://dx.doi.org/10.3389/fphar.2022.837164 Text en Copyright © 2022 Goh, Lim, Leong and Ong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Goh, Liuh Ling
Lim, Chia Wei
Leong, Khai Pang
Ong, Kiat Hoe
TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned
title TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned
title_full TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned
title_fullStr TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned
title_full_unstemmed TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned
title_short TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned
title_sort tpmt and nudt15 testing for thiopurine therapy: a major tertiary hospital experience and lessons learned
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537458/
https://www.ncbi.nlm.nih.gov/pubmed/36210828
http://dx.doi.org/10.3389/fphar.2022.837164
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