Relationship Between Thiopurine S-Methyltransferase Genotype/Phenotype and 6-Thioguanine Nucleotide Levels in 316 Patients With Inflammatory Bowel Disease on 6-Thioguanine.

Autor:	Bayoumy AB; Department of Gastroenterology and Hepatology, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands., Mulder CJJ; Department of Gastroenterology and Hepatology, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands., Loganayagam A; Department of Gastroenterology, Queen Elizabeth Hospital, Woolwich, United Kingdom., Sanderson JD; Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Anderson S; Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Boekema PJ; Department of Gastroenterology, Máxima Medical Centre, Veldhoven, The Netherlands., Derijks LJJ; Department of Clinical Pharmacy and Pharmacology, Máxima Medical Centre, Veldhoven, The Netherlands ; and., Ansari AR; Department of Gastroenterology, Surrey and Sussex NHS, East Surrey Hospital, Surrey, United Kingdom .
Jazyk:	angličtina
Zdroj:	Therapeutic drug monitoring [Ther Drug Monit] 2021 Oct 01; Vol. 43 (5), pp. 617-623.
DOI:	10.1097/FTD.0000000000000869
Abstrakt:	Background: In inflammatory bowel disease (IBD), conventional thiopurine users cease treatment in 60% of cases within 5 years, mostly because of adverse events or nonresponse. In this study, the authors aimed to investigate the role of 6-thioguanine nucleotide (TGN) measurements, geno/phenotyping of thiopurine S-methyltransferase (TPMT), and their mutual relationship with TG therapy in IBD. Methods: An international retrospective, multicenter cohort study was performed at 4 centers in the Netherlands (Máxima Medical Centre) and the United Kingdom (Guy's and St. Thomas' Hospital, Queen Elizabeth Hospital, and East Surrey Hospital). Results: Overall, 526 6-TGN measurements were performed in 316 patients with IBD. The median daily dosage of TG was 20 mg/d (range 10-40 mg/d), and the median duration of TG use was 21.1 months (SD, 28.0). In total, 129 patients (40.8%) had a known TPMT status. In the variant-type and wild-type TPMT genotype metabolism groups, median 6-TGN values were 1126 [interquartile range (IQR) 948-1562] and 467.5 pmol/8 × 10E8 red blood cells (RBCs) (IQR 334-593). A significant difference was observed between the 2 groups (P = 0.0001, t test). For TPMT phenotypes, in the slow, fast, and normal metabolism groups, the median 6-TGN values were 772.0 (IQR 459-1724), 296.0 (IQR 200-705), and 774.5 pmol/8 × 10E8 RBCs (IQR 500.5-981.5), with a significant difference observed between groups (P < 0.001, analysis of variance). Conclusions: Our findings indicated that TPMT measurements at TG initiation can be useful but are not necessary for daily practice. TPMT genotypes and phenotypes are both associated with significant differences in 6-TGN levels between metabolic groups. However, the advantage of TG remains that RBC 6-TGN measurements are not crucial to monitor treatments in patients with IBD because these measurements did not correlate with laboratory result abnormalities. This presents as a major advantage in countries where patients cannot access these diagnostic tests. Competing Interests: The authors declare no conflict of interest. (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)
Databáze:	MEDLINE
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