硫唑嘌呤不良反应文献分析

Literature Analysis of Azathioprine Adverse Reactions

目的探讨硫唑嘌呤不良反应(ADR)发生情况及相关因素。方法检索中国期刊全文数据库(CNKI)、万方数据库和中文科技期刊全文数据库(VIP)的临床研究及ADR报告。提取纳入文献中ADR患者的原患疾病、性别、年龄及ADR类型。结果627篇文献中最终纳入98篇,其中不良反应报告(A类)文献42篇报告中有55例ADR,临床研究(B类)文献56篇(449例ADR),回顾性研究共13篇(317例ADR患者)。ADR患者女性略多于男性,主要为30~59岁。A类文献中,ADR主要表现为骨髓抑制、粒细胞缺乏、白细胞减少及脱发,原患疾病主要为系统性红斑狼疮、溃疡性结肠炎、重症肌无力;ADR患者中有13例死亡。B类文献中,ADR主要表现为肝功能异常、胃肠道反应、白细胞减少、骨髓抑制、感染;原患疾病为炎症性肠病、克罗恩病、视神经性脊髓炎、溃疡性结肠炎、重症肌无力。结论硫唑嘌呤主要的ADR为血液系统损害、肝功能损害,其中骨髓抑制严重者可致命。临床可通过用药前硫代嘌呤甲基转移酶基因检测、实验室指标监测及患者用药后的密切监护,避免或减少严重ADR的发生。

Objective To analyze the adverse drug reaction( ADR) of azathioprine and relevant influence factors. Methods All clinical studies and ADR reports of azathioprine were searched from the China National Knowledge Infrastructure( CNKI) database,Chinese Wan-fang database and Chinese Periodical Full Text Database of Science and Technology. Relevant information such as types of disease,gender,the age and the category of ADR were extracted. Results In all of the 627 papers,98 were included,in which 42 controlled studies( type A) reported 55 ADR cases,56 clinical studies( type B) reported 449 ADR cases,and 13 retrospective studies( type C) reported 317 ADR cases. Of all the ADR cases,females contributed slightly more than males and could be mainly observed in the age group of 30-59 years. In type A articles,the ADR cases mainly included myelosuppression,granulocytopenia,leukopenia,and alopecia;13 of the ADR cases resulted in death and the main primary diseases of these patients were systemic lupus erythematosus,ulcerative colitis,and myasthenia gravis. In type B articles,the ADR cases mainly focused on liver dysfunction,gastrointestinal reactions,leukopenia,bone marrow suppression and infection;the primary diseases of these patients were inflammatory bowel disease,Crohn’s disease,optic neuromyelitis,ulcerative colitis,and myasthenia gravis. Conclusion The main ADRs of azathioprine are damage to the blood system and liver function,and severe bone marrow suppression can be fatal. Clinically,the incidence of severe ADR can be reduced through thiopurine methyltransferase gene testing before drug administration,monitoring of laboratory indicators,and close monitoring of patients after medication.