Mount Sinai School of Medicine, New York, NY 10029, USA.
J Pediatr Gastroenterol Nutr. 2013 Mar;56(3):333-40. doi: 10.1097/MPG.0b013e3182844705.
Thiopurines have been used in inflammatory bowel disease (IBD) for >30 years, and measurements of both thiopurine methyltransferase (TPMT) and thiopurine (TP) metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), have been readily available. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Committee on Inflammatory Bowel Disease thought it appropriate to review the present indications for use of TPMT and TP metabolite testing. Substantial evidence demonstrates that TP therapy is useful for both Crohn disease and ulcerative colitis. Review of the existing data yielded the following recommendations. TPMT testing is recommended before initiation of TPs to identify individuals who are homozygote recessive or have extremely low TPMT activity, with the latter having more reliability than the former. Individuals who are homozygous recessive or have extremely low TPMT activity should avoid the use of TPs because of concerns for significant leukopenia. TMPT testing does not predict all cases of leukopenia and has no value to predict hypersensitivity adverse effects such as pancreatitis. Any potential value to reduce the risk of malignancy has not been studied. All individuals taking TPs should have routine monitoring with complete blood cell count and white blood cell count differential to evaluate for leukopenia regardless of TPMT testing results. Metabolite testing can be used to determine adherence with TP therapy. Metabolite testing can be used to guide dose increases or modifications in patients with active disease. Consideration would include either increasing the dose, changing therapy or for those with elevated transaminases or an elevated 6-MMP, using adjunctive allopurinol to help raise 6-thioguanine metabolites and suppress formation of 6-MMP. Routine and repetitive metabolite testing has little or no role in patients who are doing well and taking an acceptable dose of a TP.
硫嘌呤已在炎症性肠病（IBD）中使用超过 30 年，并且可以方便地测量硫嘌呤甲基转移酶（TPMT）和硫嘌呤（TP）代谢物，即 6-硫鸟嘌呤核苷酸（6-TGN）和 6-甲基巯基嘌呤（6-MMP）。北美儿科学会胃肠病学、肝脏病学和营养学会（NASPGHAN）炎症性肠病委员会认为，审查 TPMT 和 TP 代谢产物检测的当前使用指征是合适的。大量证据表明，TP 治疗对克罗恩病和溃疡性结肠炎均有效。对现有数据的回顾得出以下建议。在开始使用 TPs 之前，建议进行 TPMT 检测，以确定纯合隐性或 TPMT 活性极低的个体，后者比前者更可靠。纯合隐性或 TPMT 活性极低的个体应避免使用 TPs，因为担心会出现严重的白细胞减少症。TPMT 检测不能预测所有白细胞减少症病例，也不能预测胰腺炎等过敏不良反应。减少恶性肿瘤风险的任何潜在价值尚未研究。无论 TPMT 检测结果如何，所有服用 TPs 的个体均应进行常规监测，包括全血细胞计数和白细胞分类计数，以评估白细胞减少症。代谢产物检测可用于确定是否遵循 TP 治疗。代谢产物检测可用于指导疾病活动期患者增加剂量或调整治疗方案。考虑因素包括增加剂量、改变治疗方案，或对于那些转氨酶升高或 6-MMP 升高的患者，使用别嘌呤醇辅助提高 6-硫鸟嘌呤代谢物并抑制 6-MMP 的形成。对于病情良好且服用 TP 可接受剂量的患者，常规和重复的代谢产物检测几乎没有作用或没有作用。
