Nomogram to predict primary non-response to infliximab in patients with Crohn’s disease:a multicenter study  

预测克罗恩病患者对英夫利昔单抗原发无应答的nomogram模型:一项多中心研究

作　　者：Xiao-Qi Ye Jing Cai Qiao Yu Xiao-Cang Cao Yan Chen Mei-Xin Rao Bai-Li Chen Yao He Zhi-Rong Zeng Hao Chen Yi-Mou Lin Qian Cao Min-Hu Chen Sheng-Hong Zhang 

机构地区：[1]Department of Gastroenterology,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China [2]Department of Gastroenterology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,P.R.China [3]Department of Gastroenterology,Wenzhou Central Hospital,Wenzhou,Zhejiang,P.R.China [4]Department of Gastroenterology,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,P.R.China [5]Department of Gastroenterology,Tianjin Medical University General Hospital,Tianjin,P.R.China

出　　处：《Gastroenterology Report》2021年第4期329-338,I0002,共11页胃肠病学报道（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(#81870374,#81670498);Guangdong Science and Technology(#2017A030306021);Science and Technology Innovation Young Talents of Guangdong Special Support Plan(#2016TQ03R296);the Fundamental Research Funds for the Central Universities(#19ykzd11).

摘　　要：Background:Infliximab(IFX)is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn’s disease(CD);however,9%–40%of patients do not respond to primary IFX treatment.This study aimed to construct and validate nomograms to predict IFX response in CD patients.Methods:A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort(n=240)and a validation cohort(n=103).The primary outcome was primary non-response(PNR)and the secondary outcome was mucosal healing(MH).Nomograms were constructed from the training cohort using multivariate logistic regression.Performance of nomograms was evaluated by area under the receiver-operating characteristic curve(AUC)and calibration curve.The clinical usefulness of nomograms was evaluated by decision-curve analysis.Results:The nomogram for PNR was developed based on four independent predictors:age,C-reactive protein(CRP)at week 2,body mass index,and non-stricturing,non-penetrating behavior(B1).AUC was 0.77 in the training cohort and 0.76 in the validation cohort.The nomogram for MH included four independent factors:baseline Crohn’s Disease Endoscopic Index of Severity,CRP at week 2,B1,and disease duration.AUC was 0.79 and 0.72 in the training and validation cohorts,respectively.The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model.The decision curve indicated the clinical usefulness of the PNR nomogram.Conclusions:We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients.This graphical tool is easy to use and will assist physicians in therapeutic decision-making.背景:英夫利昔单抗(IFX)治疗克罗恩病(CD)可诱导并维持临床缓解及黏膜愈合,但有9%40%的患者对IFX治疗原发无应答。本研究旨在建立并预测CD患者对IFX原发无应答的Nomogram模型。方法:2008年9月至2019年9月间在四家三甲医院接受IFX诱导治疗的343例CD患者纳入研究,并被随机分为训练队列(240例)和验证队列(103例)。主要结局指标是原发无应答,次要结局指标是黏膜愈合。基于训练队列,采用多因素逻辑回归分析建立Nomogram模型,通过曲线下面积(AUC)和校准曲线评估模型的预测价值,并采用决策曲线分析评估模型的临床实用性。结果:基于年龄、治疗2周时C反应蛋白水平、体质指数和非狭窄非穿透型(B1)病变四个独立预测因素,建立原发无应答的Nomogram预测模型,该模型在训练队列和验证队列的AUC分别为0.77和0.76。基于治疗前克罗恩病内镜严重度指数、治疗2周时C反应蛋白水平、B1型病变和病程四个独立预测因素,建立黏膜愈合的Nomogram预测模型,其在训练队列和验证队列的AUC分别为0.79和0.72。这两个Nomogram模型在训练队列和验证队列都显示出良好的拟合度,优于上述单个的预测因素以及文献报道的矩阵模型。决策曲线显示出了原发无应答Nomogram模型的临床实用性。结论:我们建立并验证了预测CD患者对IFX原发无应答和黏膜愈合的Nomogram模型,这种图像模型使用简单,并能为临床医生的治疗决策提供支持。

关 键 词：Crohn’s disease INFLIXIMAB NOMOGRAM primary non-response mucosal healing 

分 类 号：R57[医药卫生—消化系统]