Department of Dermatology, Odense University Hospital, Odense, Denmark.
Clin Exp Dermatol. 2010 Mar;35(2):140-4. doi: 10.1111/j.1365-2230.2009.03446.x. Epub 2009 Jul 29.
Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression.
To evaluate the course of azathioprine treatment in people with TPMT heterozygosity and whether this deterred clinicians in prescribing the drug.
This was a retrospective analysis on patients who had TPMT assays undertaken with the intention of treating their skin disorder with azathioprine. Primary outcome measurements were: (i) whether or not azathioprine was started, (ii) azathioprine dosage, and (iii) duration of treatment. Secondary outcome measures were the effect of the drug, any reported side-effects and reasons for not starting azathioprine.
TPMT assays were undertaken in 212 patients, of whom 90.6% were TPMT wild type and the remaining 9.4% were TPMT heterozygous. None of the patients was TPMT homozygous. Of the 192 wild-type patients, 103 (53.6%) received azathioprine, as did 7 (35%) of the 20 heterozygotes (P = 0.16). Mean azathioprine dose was 84.1 mg/day for wild-type patients and 64.3 mg/day for heterozygotes (P = 0.10). Mean treatment duration was 21.4 and 22.7 weeks for wild-type and heterozygotes, respectively (P = 0.52). Azathioprine treatment was stopped in 4 of 7 heterozygotes and 54 of 103 wild-type patients, because of side-effects, lack of effect or a combination of both. The commonest reason for not starting azathioprine treatment in heterozygous patients was their heterozygosity. For wild-type patients, the reasons were remission of disease or the patient's lack of interest in the treatment.
TPMT heterozygosity was a deterring factor for the prescription of azathioprine in our department, and the dose for wild-type patients was lower than recommended guidelines. Treatment duration and occurrence of adverse effects were similar for heterozygotes and wild-type patients.
在使用巯嘌呤甲基转移酶（TPMT）治疗前确定基因型和表型可预测哪些患者最有可能发生骨髓抑制。
评估 TPMT 杂合子接受巯嘌呤治疗的过程，以及这是否会阻止临床医生开这种药物。
这是一项回顾性分析，研究对象是接受 TPMT 检测以治疗其皮肤疾病的患者。主要观察指标为：（i）是否开始使用巯嘌呤，（ii）巯嘌呤剂量，和（iii）治疗持续时间。次要观察指标为药物的疗效、任何报告的副作用以及未开始使用巯嘌呤的原因。
对 212 名患者进行了 TPMT 检测，其中 90.6%为 TPMT 野生型，其余 9.4%为 TPMT 杂合子。无患者为 TPMT 纯合子。在 192 名野生型患者中，有 103 名（53.6%）接受了巯嘌呤治疗，20 名杂合子中有 7 名（35%）接受了治疗（P=0.16）。野生型患者的平均巯嘌呤剂量为 84.1mg/天，杂合子为 64.3mg/天（P=0.10）。野生型和杂合子的平均治疗持续时间分别为 21.4 和 22.7 周（P=0.52）。巯嘌呤治疗在 7 名杂合子中的 4 名和 103 名野生型患者中的 54 名中停止，原因是副作用、无效或两者兼有。在杂合子患者中，不开始巯嘌呤治疗的最常见原因是他们的杂合性。对于野生型患者，原因是疾病缓解或患者对治疗缺乏兴趣。
TPMT 杂合性是我们科室开具巯嘌呤处方的一个阻碍因素，且野生型患者的剂量低于推荐指南。杂合子和野生型患者的治疗持续时间和不良反应发生率相似。
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