克罗恩病患者英夫利西单抗谷浓度分布及影响因素分析  

Distribution of infliximab trough concentration and its influencing factors in patients with Crohn’s disease

作　　者：林荣芳[1] 郑玮玮[2] 林玮玮[1] 林珅 王飞羽[1] 王承党[2] 王长连[1] 黄品芳[1,3] LIN Rong-fang;ZHENG Wei-wei;LIN Wei-wei;LIN Shen;WANG Fei-yu;WANG Cheng-dang;WANG Chang-lian;HUANG Pin-fang(Department of Pharmacy,First Affiliated Hospital,Fujian Medical University,Fujian Fuzhou 350005,China;Department of Gastroenterology,First Affiliated Hospital,Fujian Medical University,Fujian Fuzhou 350005,China;Fujian Provincial Key Laboratory of Precise Diagnosis&Treatment of Tumor,Fujian Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院药学部,福建福州350005 [2]福建医科大学附属第一医院消化内科,福建福州350005 [3]福建省肿瘤精准诊疗重点实验室,福建福州350005

出　　处：《中国医院药学杂志》2021年第10期1035-1039,共5页Chinese Journal of Hospital Pharmacy

基　　金：福建省卫生计生科研人才培养项目(编号:2018-ZQN-53);福建省卫计委医学创新课题(编号:2018-CX-32);福建医科大学启航基金项目(编号:2018QH1071)。

摘　　要：目的:考察克罗恩病患者维持治疗期英夫利西单抗(IFX)稳态谷浓度的分布特点,分析影响IFX谷浓度的相关因素。方法:收集接受IFX常规给药方案治疗的克罗恩病患者相关临床资料,采用多重PCR技术结合高通量测序技术的靶向测序法获得患者相关基因多态性信息,借助酶联免疫吸附法检测IFX谷浓度,利用SPSS 20.0软件分析患者遗传因素、病理生理因素及相关临床指标对IFX谷浓度水平(低、中、高浓度)的影响。结果:研究共纳入117例患者,其中低浓度组(Cmin<3μg·mL^(-1)) 89例,中浓度组(3μg·mL^(-1)≤Cmin≤7μg·mL^(-1)) 25例,高浓度组(Cmin>7μg·mL^(-1)) 3例,3种浓度水平分别占总例数的76.1%,21.4%,2.5%。经统计分析结果显示,ALB值参数估算值0.273(P=0.002,OR=1.314),ATI(-)参数估算值1.666(P=0.039,OR=5.293)。结论:IFX维持缓解常规剂量下,患者ALB值及ATI是否阳性是影响IFX谷浓度水平的主要因素,未发现其他因素显著影响IFX谷浓度水平。临床在使用IFX时可结合患者ALB值及ATI状态适当调整方案,以提高IFX谷浓度达标效率,同时减少不良反应的发生。OBJECTIVE To explore the distribution characteristics of infliximab(IFX) steady-state trough concentration in patients with Crohn’s disease(CD) during maintenance treatment and examine the relevant influencing factors of IFX trough concentration.METHODS Clinical data were collected from CD patients on IFX conventional dosage regimen. Gene polymorphism was detected by targeted sequencing using multiple polymerase chain reaction(PCR) plus high throughput sequencing. The IFX steady-state trough concentration was determined by enzyme-linked immunosorbent assay(ELISA). SPSS20.0 software was utilized for examining the influence of genetic factors, pathophysiological factors and related clinical parameters on IFX trough low/medium/high concentration. RESULTS A total of 117 patients were recruited, including 89 patients in low concentration group(Cmin< 3 μg·mL^(-1)), 25 in medium concentration group(3 μg·mL^(-1) ≤ Cmin ≤ 7 μg·mL^(-1)) and 3 in high concentration group(Cmin> 7 μg·mL^(-1)), accounting for 76.1%, 21.4%, and 2.5% of total cases respectively. The results of statistical analysis indicated that the estimated value of albumin(ALB) was 0.273(P=0.002, OR=1.314) and the estimated value of antibody to infliximab(ATI)(-)was 1.666(P=0.039, OR=5.293).CONCLUSION ALB value and ATI antibody positivity of patients are the major influencing factors of IFX trough concentration under the routine dose of IFX in the maintenance remission stage and no other factors significantly affect the concentration level of IFX. For CD patients using IFX, the ALB value and ATI status may be combined to adjust the protocol appropriately so as to improve the efficiency of reaching the target IFX concentration and lower the occurrence of adverse reactions.

关 键 词：克罗恩病 英夫利西单抗 谷浓度 影响因素 

分 类 号：R969[医药卫生—药理学]