硫唑嘌呤治疗炎症性肠病的疗效及骨髓抑制相关不良反应分析研究  

Efficacy of azathioprine and adverse reactions related to bone marrow suppression in inflammatory bowel diseases

作　　者：郭玲 罗雪梅[2] GUO Ling;LUO Xue-mei(Department of Pharmacy,Nanjing Stomatological Hospital,Medical School of Nanjing University,Nanjing 210008;Department of Pharmacy,Affiliated Drum Tower Hospital of Nanjing University,Nanjing 210008)

机构地区：[1]南京大学医学院附属口腔医院(南京市口腔医院)药学部,南京210008 [2]南京大学医学院附属鼓楼医院药学部,南京210008

出　　处：《中南药学》2021年第1期137-142,共6页Central South Pharmacy

基　　金：江苏省药学会——天晴医院药学基金资助项目(No.Q2019042)。

摘　　要：目的探讨影响硫唑嘌呤(AZA)治疗炎症性肠病(IBD)的疗效和骨髓抑制相关不良反应的因素。方法以2017年11月-2019年6月期间消化内科收治的IBD住院患者为研究对象,收集患者基本临床资料、6-硫鸟嘌呤核苷酸(6-TGN)血药浓度以及各项生化指标,统计分析疾病活动度、患者性别、年龄、6-TGN浓度等因素对于AZA疗效和骨髓抑制相关不良反应的影响。结果 本研究共纳入131例IBD患者,入院时处于缓解期和活动期患者经AZA治疗后,白蛋白(ALB)、D-二聚体差异具有统计学意义(P<0.05),且处于缓解期患者的治疗有效率显著高于活动期患者(P<0.001);男性和女性患者的ALB、红细胞沉降率(ESR)水平的差异具有统计学意义(P<0.05),且女性患者治疗无效率更高(P=0.042);同时低6-TGN浓度组患者治疗无效率也较高。女性患者白细胞减少症发生率比男性患者高(P=0.046);发生白细胞减少的患者年龄显著偏高(P=0.004);随着6-TGN浓度的升高,白细胞水平显著降低(P=0.031),白细胞减少症发生率逐渐增高。Logistics回归分析显示疾病活动度是影响AZA疗效的关键因素,年龄是AZA致白细胞减少症发生的危险因素。结论处于疾病活动期的患者疗效较差,年龄大的患者更易出现以白细胞减少为代表的骨髓抑制相关不良反应,临床需更加关注中老年、病情较重患者的AZA安全用药,及时测定6-TGN血药浓度,避免骨髓抑制相关不良反应的发生并优化IBD治疗效果。Objective To determine the factors affecting the efficacy of azathioprine (AZA) and adverse reactions related to bone marrow suppression in the treatment of patients with inflammatory bowel disease (IBD).Methods Basic clinical data,concentrations of 6-thioguanine nucleotide (6-TGN),and biochemical parameters of inpatients with IBD admitted to the Department of Gastroenterology from November 2017 to June 2019 were collected.Disease activity,age,gender,6-TGN concentration and other factors on the efficacy and adverse reactions of AZA were analyzed.Results Totally 131 patients with IBD were included.After AZA treatment,the difference in albumin and D-dimer levels among the patients in remission and active phase on admission was significant (P <0.05),and the effective rate of patients in remission was significantly higher than that of active patients (P < 0.001).The difference in albumin and erythrocyte sedimentation rate between male and female patients was also significant (P<0.05).Females and patients with lower 6-TGN concentrations showed higher ineffective rate (P=0.042).The incidence of leukocytopenia in female patients was higher than that in male patients (P=0.046).In addition,patients with leukopenia were significantly older (P=0.004).With the increase of 6-TGN concentration,leukocyte levels decreased significantly (P=0.031),and the incidence of leukopenia gradually increased.Logistics regression analysis showed that disease activity was key to the efficacy of AZA,while age was a risk factor for ALA-induced leucopenia.Conclusion Patients in the active phase show poor efficacy,senior patients tend to have myelosuppression-related adverse reactions represented by leukopenia.We need to pay more attention to the safe use of AZA in the elderly and patients with severe IBD,timely measure the 6-TGN concentrations,avoid the occurrence of adverse reactions related to bone marrow suppression,and optimize the treatment of IBD.

关 键 词：炎症性肠病 硫唑嘌呤 6-硫鸟嘌呤核苷酸 血药浓度 骨髓抑制 

分 类 号：R96[医药卫生—药理学]