Martínez F, Nos P, Pastor M, Garrigues V, Ponce J
Servicio de Medicina Digestiva, Hospital La Fe, Valencia, Spain.
Rev Esp Enferm Dig. 2001 Dec;93(12):769-78.
To know the type, frequency and time course for the occurrence of adverse events in our series of patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine.
92 consecutive patients were treated with azathioprine. 70 of them (55 Crohn's disease, 14 ulcerative colitis and 1 undetermined colitis) were suitable for analysis.
We observed 23 adverse reactions in 21 patients. Adverse events were as follows: haematological 11.4%, digestive intolerance 11.4%, infection 7.1%, and pancreatitis 2.8%. The prevalence was increased among ulcerative colitis patients (57.8 vs. 21.8%) (p = 0.02). There were no statistical differences in the prevalence of adverse events respective of the age, gender or location of disease. Digestive intolerance and pancreatitis occurred within the first 6 months of therapy, whereas haematological side effects occurred between 3 months and 4 years after therapy onset. Early occurrence (but not late occurrence) was associated with thiopurine methyltransferase (TMPT) activity levels. All infections took place between 8 months and 5 years of treatment. Azathioprine was definitively withdrawn due to side effects in 9 cases (12.8%).
The frequency of adverse events in our study is similar to that reported in previous studies. Azathioprine withdrawal is required in almost half of the cases because of toxicity. Frequency of side effects is increased in patients with ulcerative colitis. The variability in time course makes clinical-biological monitoring mandatory.
了解在我们使用硫唑嘌呤或6-巯基嘌呤治疗的炎症性肠病患者系列中不良事件的类型、发生频率及时间进程。
92例连续患者接受硫唑嘌呤治疗。其中70例（55例克罗恩病、14例溃疡性结肠炎和1例未定型结肠炎）适合分析。
我们在21例患者中观察到23例不良反应。不良事件如下：血液学不良反应占11.4%，消化不耐受占11.4%，感染占7.1%，胰腺炎占2.8%。溃疡性结肠炎患者中的发生率有所增加（57.8%对21.8%）（p = 0.02）。不良事件的发生率在年龄、性别或疾病部位方面无统计学差异。消化不耐受和胰腺炎发生在治疗的前6个月内，而血液学副作用发生在治疗开始后的3个月至4年之间。早期发生（而非晚期发生）与硫嘌呤甲基转移酶（TMPT）活性水平相关。所有感染均发生在治疗的8个月至5年之间。因副作用，9例（12.8%）患者最终停用了硫唑嘌呤。
我们研究中不良事件的发生率与先前研究报道的相似。由于毒性，几乎一半的病例需要停用硫唑嘌呤。溃疡性结肠炎患者的副作用发生率增加。时间进程的变异性使得临床生物学监测成为必需。
