英夫利西单克隆抗体治疗克罗恩病的真实世界疗效预测研究  

Real world efficacy prediction analysis of infliximab in the treatment of Crohn's disease

作　　者：吕彩云 陈泳渝 严锋枫 皮斯杰 刘瑶[2,4] 陈瑞东[1] 唐文[1] 张红杰[3] Lyu Caiyun;Chen Yongyu;Yan fengfeng;Pi Sijie;Liu Yao;Chen Ruidong;Tang Wen;Zhang Hongjie(Department of Gastroenterology,the Second Affiliated Hospital,Soochow University,Suzhou 215004,China;Department of Pathology,School of Biology and Basic Medical Sciences,Suzhou Medical College,Soochow University,Suzhou 215123,China;Department of Gastroenterology,the First Affliated Hospital,Nanjing Medical University,Nanjing 210029,China;Department of Pathology,the Second Affiliated Hospital,Soochow University,Suzhou 215004,China)

机构地区：[1]苏州大学附属第二医院消化科,苏州215004 [2]苏州大学基础医学与生物科学学院病理学系,苏州215123 [3]南京医科大学第一附属医院消化科,南京210029 [4]苏州大学附属第二医院病理科,苏州215004

出　　处：《中华炎性肠病杂志（中英文）》2024年第5期378-383,共6页Chinese Journal of Inflammatory Bowel Diseases

基　　金：国家自然科学基金面上项目(81972259);苏州市2022年度第二十八批科技发展计划(医疗卫生科技创新)指导性项目(SKYD2022033)。

摘　　要：目的探讨影响英夫利西单克隆抗体(IFX)治疗克罗恩病(CD)患者疗效的因素。方法本研究为巢式病例对照研究,纳入苏州大学附属第二医院2015年11月至2021年4月和南京医科大学第一附属医院2015年11月至2022年12月经IFX治疗的CD患者,均随访至2023年6月。根据随访期间患者临床表现和肠镜影像的变化将其分为失应答组和有效组。回顾性收集并比较两组患者在入院时、诱导治疗前后炎症指标和诱导治疗后药物谷浓度及抗药抗体浓度等检验数据。使用logistic回归模型识别影响IFX失应答的潜在因素,并采用随机森林机器学习方法识别预测IFX疗效的变量特征值,最后采用ROC曲线评估模型的准确性。结果纳入147例IFX治疗的CD患者,包括苏州大学附属第二医院58例,南京医科大学第一附属医院89例,其中失应答组38例,有效组109例。IFX失应答组患者的诱导治疗后药物谷浓度更低(P<0.001)、抗药抗体浓度更高(P<0.001)、诱导期红细胞沉降率(ESR)下降幅度低(P<0.001)。单因素和多因素Logistic回归模型显示IFX药物谷浓度和诱导期ESR变化幅度与失应答风险有关。诱导期结束后,药物谷浓度每增加1个单位(即1μg/ml),IFX失应答的风险降低23%(RR=0.77,95%CI=0.68~0.89)。诱导治疗后与治疗前的ESR比值每升高1倍,IFX失应答的风险升高1.43倍(RR=2.43,95%CI=1.48~4.00)。随机森林机器学习显示药物谷浓度低于1.5μg/ml可预测IFX失应答,ROC曲线下面积为0.722。结论IFX诱导治疗后药物谷浓度低可以预测IFX失应答,诱导治疗期ESR下降不明显也和IFX失应答显著相关。Objective To identify early predictors of factors influencing the efficacy of infliximab(IFX)treatment in patients with Crohn's disease(CD).Methods This study is a nested case-control study,including CD patients treated with IFX at the Second Affiliated Hospital of Soochow University from November 2015 to April 2021 and at the First Affiliated Hospital of Nanjing Medical University from November 2015 to December 2022.All the patients were followed up until June 2023 and categorized into IFX non-response and treatment-effective groups based on changes in clinical symptoms and endoscopic image during the follow-up.Laboratory data of inflammatory markers,post-induction trough IFX concentration and antibody levels in both groups were retrospectively collected and compared.Logistic regression models were employed to identify potential factors associated with the risk of IFX non-responsiveness.Machine learning using random forest analysis was utilized to quantitatively assess the predictive features for IFX treatment efficacy and ROC curves was used to evaluate the model's accuracy.Results This study included 147 CD patients undergoing IFX treatment,with 58 from the Second Affiliated Hospital of Soochow University and 89 from the First Affiliated Hospital of Nanjing Medical University.Among them,38 were classified as the IFX non-response group,and 109 as the effective group.Patients in the IFX non-response group had lower trough concentration(P<0.001),higher antibody levels(P<0.001),and a less pronounced reduction in ESR during the induction therapy(P<0.001).Univariate and multi-variate Logistic regression models demonstrated that IFX trough concentration and the ratio of ESR before and after induction therapy was associated with the risk of non-responsiveness.After the induction period,for each unit increase in IFX trough concentration(1μg/ml),the risk of IFX non-response decreased by 23%(RR=0.77,95%CI=0.68-0.89),while each doubling of the ESR ratio after induction was associated with a 1.43-fold increase in the risk

关 键 词：克罗恩病 英夫利西单克隆抗体 红细胞沉降率 

分 类 号：R574[医药卫生—消化系统]