Konidari Anastasia, Matary Wael El
Anastasia Konidari, Department of Paediatric Gastroenterology, Alder Hey Children's NHS Foundation Trust, Liverpool L12 2AP, United Kingdom.
World J Gastrointest Pharmacol Ther. 2014 May 6;5(2):63-76. doi: 10.4292/wjgpt.v5.i2.63.
Thiopurines are widely used for maintenance treatment of inflammatory bowel disease. Inter-individual variability in clinical response to thiopurines may be attributed to several factors including genetic polymorphisms, severity and chronicity of disease, comorbidities, duration of administration, compliance issues and use of concomitant medication, environmental factors and clinician and patient preferences. The purpose of this review is to summarise the current evidence on thiopurine safety and toxicity, to describe adverse drug events and emphasise the significance of drug interactions, and to discuss the relative safety of thiopurine use in adults, elderly patients, children and pregnant women. Thiopurines are safe to use and well tolerated, however dose adjustment or discontinuation of treatment must be considered in cases of non-response, poor compliance or toxicity. Drug safety, clinical response to treatment and short to long term risks and benefits must be balanced throughout treatment duration for different categories of patients. Treatment should be individualised and stratified according to patient requirements. Enzymatic testing prior to treatment commencement is advised. Surveillance with regular clinic follow-up and monitoring of laboratory markers is important. Data on long term efficacy, safety of thiopurine use and interaction with other disease modifying drugs are lacking, especially in paediatric inflammatory bowel disease. High quality, collaborative clinical research is required so as to inform clinical practice in the future.
硫嘌呤类药物广泛用于炎症性肠病的维持治疗。个体对硫嘌呤类药物临床反应的差异可能归因于多种因素,包括基因多态性、疾病的严重程度和病程、合并症、给药持续时间、依从性问题以及联合用药情况、环境因素以及临床医生和患者的偏好。本综述的目的是总结关于硫嘌呤类药物安全性和毒性的现有证据,描述药物不良事件并强调药物相互作用的重要性,并讨论硫嘌呤类药物在成人、老年患者、儿童和孕妇中使用的相对安全性。硫嘌呤类药物使用安全且耐受性良好,然而,在无反应、依从性差或出现毒性的情况下,必须考虑调整剂量或停止治疗。在整个治疗期间,必须平衡不同类别患者的药物安全性、临床治疗反应以及短期至长期的风险和益处。治疗应根据患者需求进行个体化和分层。建议在开始治疗前进行酶学检测。定期门诊随访监测和实验室指标监测很重要。关于硫嘌呤类药物长期疗效、使用安全性以及与其他改善病情药物相互作用的数据尚缺乏,尤其是在儿童炎症性肠病方面。需要开展高质量的协作性临床研究,以便为未来的临床实践提供依据。