Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease
Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease
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DOI：
10.1097/00054725-200407000-00003
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发表时间：
2004-07-01
影响因子：
4.9
通讯作者：
Lashner, B
中科院分区：
文献类型：
--
作者：
Achkar, JP;Stevens, T;Lashner, B
目的：关于如何在炎症性肠病患者中最佳剂量和治疗监测6-巯基嘌呤或硫唑嘌呤存在一些不确定性。本研究的目的是评估临床反应，6-巯基嘌呤代谢物水平，相对白细胞减少症，和药物dose.Methods：60例炎症性肠病谁是稳定剂量的6-巯基嘌呤或硫唑嘌呤3个月，谁有测量6-巯基嘌呤代谢物水平进行了评价。将患者分为完全应答者（N = 24）、部分应答者（N = 7）或无应答者（N = 29）。结果：当我们分析基于药物分子量的调整剂量时，药物剂量与临床应答相关（P = 0.002）。6-硫鸟嘌呤水平也与临床反应相关（P = 0.003），反应者和无反应者之间的最大差异见于6-硫鸟嘌呤水平大于260 pmol/8 × 10（8）RBC。相对白细胞减少（定义为白色细胞计数低于5.0或4.0 K/uL）与临床反应无关（P分别为0.13和0.77）。药物剂量和6-硫鸟嘌呤水平与炎症性肠病患者对6-巯基嘌呤或硫唑嘌呤的临床反应有关。2.对于6-硫鸟嘌呤水平，存在相当数量的重叠，但在> 260 pmol/8 x 10（8）RBC的水平下观察到应答者和非应答者之间的最大差异。3.相对白细胞减少症与临床反应不相关。
Objectives: There is some uncertainty regarding how to best dose and therapeutically monitor 6-mercaptopurine or azathioprine in patients with inflammatory bowel disease. The purpose of this study was to assess the relation between clinical response, 6-mercaptopurine metabolite levels, relative leukopenia, and drug dose.Methods: 60 patients with inflammatory bowel disease who were on stable doses of 6-mercaptopurine or azathioprine for 3 months and who had measurements of 6-mercaptopurine metabolite levels were evaluated. Patients were classified as complete responders (N = 24), partial responders (N = 7), or non-responders (N = 29).Results: Drug dose was associated with clinical response when we analyzed adjusted doses based on molecular drug weight (P = 0.002). 6-Thioguanine levels also were associated with clinical response (P = 0.003) and the maximal difference between responders and non-responders was seen at 6-thioguanine levels greater than 260 pmol/8 x 10(8) RBC. Relative leukopenia, defined as white blood cell count less than either 5.0 or 4.0 K/uL, was not associated with clinical response (P = 0.13 and 0.77 respectively).Conclusions: 1. Drug dose and 6-thioguanine levels are related to clinical response in patients with inflammatory bowel disease on 6-mercaptopurine or azathioprine. 2. For 6-thioguanine levels, there is a fair amount of overlap, but maximal differentiation between responders and non-responders is seen at levels > 260 pmol/8 x 10(8) RBC. 3. Relative leukopenia does not correlate well with clinical response.