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

Liuh Ling Goh; Chia Wei Lim; Khai Pang Leong; Kiat Hoe Ong

doi:10.3389/fphar.2022.837164

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

Front Pharmacol. 2022 Sep 23:13:837164. doi: 10.3389/fphar.2022.837164. eCollection 2022.

Authors

Liuh Ling Goh¹, Chia Wei Lim¹, Khai Pang Leong^{1

2}, Kiat Hoe Ong^{1

3}

Affiliations

¹ Molecular Diagnostic Laboratory, Personalized Medicine Service, Tan Tock Seng Hospital, Singapore, Singapore.
² Department of Rheumatology, Allergy & Immunology, Tan Tock Seng Hospital, Singapore, Singapore.
³ Department of Haematology, Tan Tock Seng Hospital, Singapore, Singapore.

Abstract

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.

Keywords: NUDT15; TPMT; pharmacogenetics; precision medicine; thiopurine.