硫唑嘌呤治疗炎症性肠病的不良反应分析

Adverse Effects of Azathioprine in the Treatment of Inflammatory Bowel Disease

目的了解硫唑嘌呤(AZA)治疗炎症性肠病不良反应的类型、发生率、发生时间及转归。方法 回顾性分析1995年3月～2009年9月北京协和医院接受硫唑嘌呤治疗的85例炎症性肠病患者的病历资料,其中溃疡性结肠炎37例,克罗恩病48例。结果 37例(43.5%)患者出现不良反应共43次,其中48%(20/43)的不良反应发生在用药1个月内。常见不良反应为:血液系统损害16例,感染10例,胃肠道反应9例,肝功能损害5例,其他不良反应有头晕或头痛、乏力、关节痛、皮疹。15%患者(11/85)因不良反应停药,其中白细胞减少3例,感染、胃肠道反应、头晕或头痛各2例,关节痛、皮疹各1例;55%(6/11)停药发生在用药1月内。Logistic回归分析显示:女性患者白细胞减少发生率是男性患者的5.98倍,增加AZA剂量≥75mg/d的患者白细胞降低的总发生率是未增加者的4.89倍。患者年龄、性别、用药剂量、联用SASP、联用激素及用药时间相对感染的发生率、AZA不耐受对总不良反应发生率没有影响。所有不良反应自行恢复或相应治疗后恢复。结论 AZA治疗炎症性肠病因不良反应停药的比例约15%,应特别注意对用药第1个月的不良反应的监测。未出现不可逆或致死性不良反应。女性患者和增加用药剂量者白细胞降低的风险增加。

Objective The aims of this study were to probe the type,frequency,and time of appearance of the adverse events in the patients with inflammatory bowel disease treated with azathioprine.Methods We retrospectively analyzed the data of 85 patients（48 Crohn＇s disease,37 ulcerative colitis） treated with azathioprine from March,1995 to September,2009 in Peking union medical hospital.Results We observed 43 adverse reactions in 37 patients,and 48 percent of adverse reactions occurred within the first month of therapy.The main adverse events were as follows：haematological disorder（16 patients）,infection（10 patients）,digestive intolerance（9 patients）,hepatic dysfunction（5 patients）.Other adverse reaction included headache,dizziness,fatigue,joint pain and rash.Withdrawal of azathioprine caused by side effects occurred in 11 patients（leucopenia,5 patients;infection,2 patients;digestive intolerance,2 patients;headache,2 patients;dizziness,2 patients;joint pain,1 patient;rash,1 patient）.55 percent of withdrawal occurred first month after incicte of therapy.Logistic regression analysis showed leucopenia occured 5.98 times more in female patients than in male patients,and 4.89 times more in patients treated with AZA at a dose of 75 mg/day or more than those treated at a dose less than 75 mg/day.There were no statistical differences in the prevalence of adverse events and infection respective of the age,gender,dosage,course of treatment,combined with SASP or corticosteroid.All adverse reactions recovered with or without proper treatment.Conclusion It is especially important to monitor the adverse events of AZA within the first month of therapy.There are no irreversible and fatal adverse reactions in this study.The risk of leucopenia increases in female patients and patients treated with AZA at a higher dosage.