Safety of Thiopurine Therapy in Inflammatory Bowel Disease: Long-term Follow-up Study of 3931 Patients
Safety of Thiopurine Therapy in Inflammatory Bowel Disease: Long-term Follow-up Study of 3931 Patients
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DOI：
10.1097/mib.0b013e318281f28f
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发表时间：
2013-06-01
影响因子：
4.9
通讯作者：
Gisbert, Javier P.
中科院分区：
文献类型：
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作者：
Chaparro, Maria;Ordas, Ingrid;Gisbert, Javier P.
背景：评价硫嘌呤类药物在炎症性肠病患者中的安全性。为了确定与硫嘌呤诱导的不良事件的发展相关的预测因素。方法：不良事件的长期发生率估计从前瞻性维护的西班牙全国数据库中使用Kaplan-Meier分析的患者。考克斯回归分析，以确定潜在的预测因素的不良事件。95%的患者使用硫唑嘌呤。硫嘌呤的中位随访时间为44个月（范围，0-420）。不良事件发生在开始治疗后中位1个月。不良事件的累积发生率为26%，每患者-年治疗的年风险为7%。最常见的不良事件是恶心（8%）、肝毒性（4%）、骨髓毒性（4%）和胰腺炎（4%）。4例患者患有淋巴瘤。女性和克罗恩病增加了恶心的风险。女性肝毒性风险较低，克罗恩病风险较高。在接受巯基嘌呤治疗的患者和女性中，骨髓毒性的风险显著较高。克罗恩病的胰腺炎风险较高。总体而言，17%的患者因不良事件而停止硫嘌呤治疗。百分之三十七的这些患者开始硫嘌呤再次和40%的人有不良事件against.Conclusions：多达1的4例患者硫嘌呤治疗在随访期间有不良事件。相对较高比例的患者（17%）由于不良事件而不得不停止硫嘌呤治疗。然而，超过一半的患者在因不良事件而停药后重新开始巯基嘌呤治疗，并能耐受。一些不良事件的预测因素已经确定。
Background:To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events.Methods:Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events.Results:Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again.Conclusions:As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.