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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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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. |
format | Online Article Text |
id | pubmed-9537458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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