在炎症性肠病(IBD)中,传统的硫嘌呤使用者在5年内停止治疗的病例中有60%,主要是因为不良事件或无应答。在这项研究中,作者旨在研究6-硫代鸟嘌呤核苷酸(TGN)测量的作用,硫嘌呤S-甲基转移酶(TPMT)的基因/表型,及其与IBDTG治疗的相互关系。
国际回顾展,多中心队列研究在荷兰(马西玛医疗中心)和英国(盖伊和圣托马斯医院,伊丽莎白女王医院,和东萨里医院)。
总的来说,对316例IBD患者进行了526次6-TGN测量。TG的中位日剂量为20mg/d(范围为10-40mg/d),TG使用的中位持续时间为21.1个月(SD,28.0)。总的来说,129例患者(40.8%)具有已知的TPMT状态。在变异型和野生型TPMT基因型代谢组中,中位6-TGN值分别为1126[四分位距(IQR)948-1562]和467.5pmol/8×10E8红细胞(RBC)(IQR334-593).两组之间观察到显着差异(P=0.0001,t检验)。对于TPMT表型,在缓慢的,快,和正常代谢组,6-TGN的中值为772.0(IQR459-1724),296.0(IQR200-705),和774.5pmol/8×10E8红细胞(IQR500.5-981.5),组间观察到显著差异(P<0.001,方差分析)。
我们的发现表明,TG开始时的TPMT测量可能是有用的,但不是日常实践所必需的。TPMT基因型和表型均与代谢组之间6-TGN水平的显着差异相关。然而,TG的优势在于,RBC6-TGN测量对于IBD患者的治疗监测并不重要,因为这些测量与实验室结果异常无关.在患者无法获得这些诊断测试的国家中,这是一个主要优势。
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.
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).
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).
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.