Gastrointestinal Unit, Centre for Molecular Medicine, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK.
Intern Med J. 2013 Mar;43(3):278-86. doi: 10.1111/j.1445-5994.2012.02936.x.
The thiopurines azathioprine and 6-mercaptopurine are recommended for maintenance of remission in inflammatory bowel disease (IBD). Measurement of concentrations of the metabolites 6-thioguanine nucleotide and 6-methylmercaptopurine helps delineate interindividual variation in metabolism that may underlie variability in efficacy and toxicity.
We aimed to perform a retrospective observational study to determine the utility of thiopurine metabolite testing following its introduction into South Australia.
All patients having thiopurine metabolite tests done at Flinders Medical Centre between November 2008 and January 2010 were identified. Case notes of patients with testing done in the context of treatment for IBD were interrogated to determine the reason for testing, clinical context and outcome.
One hundred and fifty-one patients were identified with thiopurine metabolite testing for IBD with 157 testing episodes. Eighty (51.0%) had testing done for flare or inefficacy, 18 (11.5%) for adverse effects, 5 (3.2%) for a combination of inefficacy and adverse effects, and 54 (34.4%) for routine or other reasons. Testing was followed by improved outcomes of increased efficacy, reduced toxicity or change to alternative therapy in 55.0% of the inefficacy/flare group, 27.8% of the suspected adverse reaction group, 60.0% of the combination group, and 13.0% of the routine/other group. Allopurinol was used as cotherapy in 16 patients and led to marked improvements in metabolite concentrations.
Thiopurine metabolite testing has quickly become established in South Australia. When used for inefficacy or adverse effects, it often leads to improved outcomes. Prospective studies are needed to determine whether routine testing to guide dosing is of benefit.
硫嘌呤类药物巯嘌呤和 6-巯基嘌呤被推荐用于维持炎症性肠病（IBD）的缓解。测量代谢产物 6-硫鸟嘌呤核苷酸和 6-甲基巯基嘌呤的浓度有助于描绘代谢个体间的差异，这可能是疗效和毒性变异性的基础。
我们旨在进行一项回顾性观察研究，以确定硫嘌呤代谢产物检测在引入南澳大利亚后的实用性。
确定 2008 年 11 月至 2010 年 1 月在弗林德斯医疗中心进行硫嘌呤代谢产物检测的所有患者。对在 IBD 治疗背景下进行检测的患者的病历进行查询，以确定检测的原因、临床背景和结果。
共确定了 151 例 IBD 患者进行了硫嘌呤代谢产物检测，共进行了 157 次检测。80 例（51.0%）因疾病发作或疗效不佳进行了检测，18 例（11.5%）因不良反应进行了检测，5 例（3.2%）因疗效不佳和不良反应联合进行了检测，54 例（34.4%）因常规或其他原因进行了检测。在疗效不佳/发作组中，55.0%的患者检测后疗效提高、毒性降低或改用替代疗法，在疑似不良反应组中，27.8%的患者检测后疗效提高、毒性降低或改用替代疗法，在联合组中，60.0%的患者检测后疗效提高、毒性降低或改用替代疗法，在常规/其他组中，13.0%的患者检测后疗效提高、毒性降低或改用替代疗法。16 例患者联合使用别嘌呤醇作为辅助治疗，导致代谢产物浓度显著改善。
硫嘌呤代谢产物检测在南澳大利亚迅速得到确立。当用于治疗疗效不佳或不良反应时，它通常会带来更好的结果。需要前瞻性研究来确定常规检测以指导剂量是否有益。
