血清英夫利西单克隆抗体谷浓度联合C反应蛋白水平对英夫利西单克隆抗体继发性失应答的预测  

Predictive value of the combination of infliximab trough levels and C reactive protein in secondary loss of response to infliximab after induced remission

作　　者：张启维 孙颖[1] 王天蓉[1] 沈骏[1] 郑青[1] 冉志华[1] Zhang Qiwei;Sun Ying;Wang Tianrong;Shen Jun;Zheng Qing;Ran Zhihua(Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicin;Shanghai Institute of Digestive Diseas;Shanghai Inflammatory Bowel Disease Research Center, Shanghai 200127, Chin)

机构地区：[1]上海交通大学医学院附属仁济医院消化内科上海市消化疾病研究所上海市炎症性肠病研究中心,200127

出　　处：《中华消化杂志》2018年第4期232-237,共6页Chinese Journal of Digestion

基　　金：国家自然科学基金（81770545、81470820）

摘　　要：目的 评估英夫利西单克隆抗体（IFX）开始诱导治疗14周时的血清IFX谷浓度和CRP水平在预测IFX维持治疗CD患者发生继发性失应答方面的作用.方法 纳入2015年11月至2016年10月接受IFX治疗的43例CD患者,在第0、2、6周予5 mg/kg静脉滴注IFX进行诱导治疗,随后每隔8周予相同剂量的IFX进行长期维持治疗.在第1次注射IFX后14周时检测患者血清IFX谷浓度和CRP水平,采用 Harvey-Bradshaw指数评分对CD患者的疾病活动度进行评估.根据随访结果,将入组患者分成失应答组和持续应答组,分析两组患者诱导治疗开始14周时的IFX谷浓度和CRP水平的差异.统计学分析采用Mann-Whitney U检验和ROC曲线.结果 经过中位随访时间54周后,43例CD患者中,18例（41.9%）对IFX持续应答,11例（25.6%）对IFX失应答.在IFX诱导治疗后14周时,失应答组血清 IFX 谷浓度为2.30 μg/mL（0.52 μg/mL,2.92 μg/mL）,低于持续应答组的5.10 μg/mL （3.54 μg/mL,9.34 μg/mL）,差异有统计学意义（Z= -3.236,P=0.001）;失应答组血清CRP水平为3.10 mg/L（0.38 mg/L,21.70 mg/L）,高于持续应答组的0.51 mg/L（0.27 mg/L,1.50 mg/L）,差异有统计学意义（Z= -1.732,P=0.015）.ROC曲线分析显示,诱导治疗开始后14周时,血清IFX谷浓度和CRP水平预测失应答的 AUC值分别为0.864（95% CI 0.728-0.999）和0.694（95% CI 0.469-0.920）,灵敏度分别为83.3% 和81.8%,特异度分别为94.4% 和54.5%,准确度最高临界值分别为3.115 μg/mL和5.93 mg/L.结论 CD患者在 IFX诱导治疗开始后14周时的血清 IFX 谷浓度〈3.115 μg/mL和CRP水平〉5.93 mg/L可能是IFX维持治疗期间发生失应答的有效预测因素.Objective To evaluate the role of infliximab trough levels（IFX-TL）and C reactive protein（CRP）concentration in prediction secondary loss of response（LOR）to infliximab（IFX）in patients with Crohn′s disease（CD）during IFX maintenance therapy since 14 weeks after induced treatment.Methods From November 2015 to October 2016,43 CD patients received IFX treatment were enrolled.IFX was initially given at zero,two,and six weeks at 5 mg/kg as induced therapy,and then the same dose was given every eight weeks as long-term maintenance treatment.Serum IFX-TL and CRP concentration were measured at 14thweek after the first IFX injection.The disease activity of CD was assessed by the Harvey-Braddshaw index.According to the follow-up results,the enrolled patients were divided into LOR group and continuous response group,and then the differences in IFX-TL and CRP concentrations at the 14thweek after induced therapy were compared between two groups.Mann-Whitney U test and receiver operating characteristic（ROC）curve were performed for statistical analysis.Results After a median 54 weeks of follow-up,18（41.9%）of 43 CD patients achieved a sustained response to IFX therapy,while 11 patients（25.6%）were LOR to IFX therapy.At the 14thweek after induced therapy,serum IFX-TL of LOR group was 2.30 μg/mL（0.52 μg/mL,2.92 μg/mL）,which was lower than that of continuous response group（5.10 μg/mL（3.54 μg/mL,9.34 μg/mL））,and the difference was statistically significant（Z=-3.236,P=0.001）.The CRP concentration of LOR group was 3.10 mg/L （0.38 mg/L,21.70 mg/L）,which was higher than that of continuous response group（0.51 mg/L（0.27 mg/L, 1.50 mg/L））,and the difference was statistically significant（Z=-1.732,P=0.015）.The results of ROC curve analysis indicated that at 14thweek after induced therapy the area under curve（AUC）value of predictive role of serum IFX-TL and CRP level in LOR to IFX was 0.864（95% confidence interval（CI）0.728 to 0.999）,sensitivities were 83.3% and 81.

关 键 词：CROHN病 C反应蛋白 英夫利西单克隆抗体 谷浓度 继发性失应答 

分 类 号：R446.6[医药卫生—诊断学] R574[医药卫生—临床医学]