Roblin X, Serre-Debeauvais F, Phelip J-M, Faucheron J-L, Hardy G, Chartier A, Helluwaert F, Bessard G, Bonaz B
Département d'Hépato-Gastroentérologie, CHU de Grenoble, 38043 Grenoble Cedex, France.
Aliment Pharmacol Ther. 2005 Apr 1;21(7):829-39. doi: 10.1111/j.1365-2036.2005.02419.x.
6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine.
The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine.
Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients.
A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 x 10(8) RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 x 10(8) RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells was a predictive factor of favourable clinical remission.
Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 x 10(8) red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).
6-硫鸟嘌呤核苷酸是硫唑嘌呤的活性代谢产物。
本研究旨在评估接受硫唑嘌呤治疗的激素依赖型克罗恩病和溃疡性结肠炎患者在不使用类固醇情况下的临床缓解率、中长期疗效以及监测6-硫鸟嘌呤时临床反应的预测因素。
前瞻性纳入接受或未接受硫唑嘌呤治疗（后期每日剂量为2.5mg/kg）的激素依赖型克罗恩病和溃疡性结肠炎患者。在第1个月和第2个月监测6-硫鸟嘌呤，此后每3个月监测1年。调整硫唑嘌呤剂量以使6-硫鸟嘌呤水平达到>250pmol/8×10⁸红细胞。对部分患者评估硫嘌呤甲基转移酶基因型/表型。
共前瞻性纳入106例患者（70例克罗恩病，36例溃疡性结肠炎）。在意向性分析中，接受硫唑嘌呤治疗的患者在6个月和12个月时不使用类固醇的临床缓解率分别为72%和59%。6-硫鸟嘌呤>250pmol/8×10⁸红细胞的患者缓解率显著更高（6个月和12个月时分别为86%和69%；P<0.01）。纳入时接受或未接受硫唑嘌呤治疗的克罗恩病和溃疡性结肠炎患者之间未观察到显著差异。单因素分析中，无克罗恩病狭窄、6-硫鸟嘌呤水平>250pmol/8×10⁸红细胞以及红细胞平均体积增加是临床反应良好的预测因素。多因素分析中，仅6-硫鸟嘌呤水平>250pmol/8×10⁸红细胞是临床缓解良好的预测因素。
在接受硫唑嘌呤治疗的激素依赖型克罗恩病和溃疡性结肠炎患者中，监测6-硫鸟嘌呤以使水平达到>250pmol/8×10⁸红细胞时，不使用类固醇实现临床缓解的可能性显著更高（6个月和12个月时分别为86%和69%）。
