硫唑嘌呤治疗炎症性肠病患者的不良反应分析

Analysis of adverse drug reactions of azathioprine in the treatment of patients with inflammatory bowel disease

目的 总结炎症性肠病患者服用硫唑嘌呤药物(AZA)产生不良反应的现状,处理措施及预后.方法 对1994年12月至2015年9月在浙江大学医学院附属邵逸夫医院接受硫唑嘌呤治疗的364例炎症性肠病患者的病历资料进行回顾性分析,其中克罗恩病292例,溃疡性结肠炎72例.结果 364例炎症性肠病患者中147例(40.4%)患者出现不良反应共178例次,包括骨髓毒性74例,肝功能异常31例,胃肠道反应18例,感染14例,关节痛11例,其他不良反应有胰腺炎、头晕头痛、皮疹、脱发、发热等共30例.其中发生在用药1个月内的不良反应占42.1%(75/178).因不良反应停药的患者占20.1%(73/364),停药患者中的52.1%(38/73)发生在用药1个月内.所有不良反应或自行好转或相应处理后恢复,未出现不可逆的严重不良反应.结论 硫唑嘌呤治疗炎症性肠病不良反应发生率及停药率较高,且表现多样,以骨髓毒性及肝损害多见,需重视不良反应的监测,尤其是用药早期.特殊感染、胰腺炎及粒细胞缺乏病例相对少见.硫唑嘌呤药物治疗炎症性肠病相对安全.

Objective To summarize the current situation,management and prognosis of adverse drug reactions(ADRs)of azathioprine(AZA)in treating patients suffered from inflammatory bowel disease(IBD).Methods A retrospective analysis was conducted based on the data of 364 IBD patients,including 292 cases of Crohn′s disease and 72 cases of ulcerative colitis,who were treated with AZA from December 1994 to September 2015 at Sir Run Run Shaw Hospital.Results Among the 364 patients with inflammatory bowel disease,a total of 178 adverse events were observed in 147 patients(40.4%of all the patients),including myelotoxicity in 74 cases,hepatic dysfunction in 31 cases,gastrointestinal reaction in 18 cases,infection in 14 cases,arthralgia in 11 cases,besides,other 30 adverse events included pancreatitis,dizziness,headache,tetter,alopecia,fever and so on.42.1%(75/178)of adverse events occurred within the first month of therapy.20.1%of patients(73/364)stopped the administration because of the side effects,and among them,52.1%(38/73)of patients stopped in the first month of therapy.All the adverse reactions could be self-recovered or recovered under proper treatment.There were no irreversible and fatal cases in this study.Conclusions Rates of adverse reactions and drug-withdraw in IBD patients treated by AZA are quite high.The clinical manifestations of ADRs are varied,usually in myelotoxicity and abnormal liver function.Close attention should be paid to the ADRs caused by AZA,especially at the beginning of therapy.ADRs about special infections,pancreatitis and agranulocytosis are rare.AZA is relatively safe.