克罗恩病患者抗肿瘤坏死因子-α单克隆抗体治疗中发生原发性失应答的危险因素分析与预测模型构建  

Analysis on the risk factors and establishment of a prediction model for primary non-response to the treatment of anti-tumor necrosis factor-α monoclonal antibody in Crohn′s disease patients

作　　者：曾愫琦 刘传 苏文豪 张吉翔[1] 安萍[1] 叶梅[2] 董卫国[1] Zeng Suqi;Liu Chuan;Su Wenhao;Zhang Jixiang;An Ping;Ye Mei;Dong Weiguo(Department of Gastroenterology,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Gastroenterology,Zhongnan Hospital of Wuhan University,Wuhan 430071,China)

机构地区：[1]武汉大学人民医院消化内科,武汉430060 [2]武汉大学中南医院消化内科,武汉430071

出　　处：《中华消化杂志》2023年第1期31-39,共9页Chinese Journal of Digestion

摘　　要：目的探究克罗恩病患者抗肿瘤坏死因子-α(TNF-α)单克隆抗体(简称单抗)治疗中发生原发性失应答(PNR)的独立危险因素并构建预测模型。方法纳入2018年12月1日至2022年7月31日于武汉大学人民医院行抗TNF-α单抗治疗的103例克罗恩病患者(建模组),选择武汉大学中南医院同期行抗TNF-α单抗治疗的109例克罗恩病患者(验证组)。收集所有患者首次行抗TNF-α单抗治疗前的基线临床资料,包括C反应蛋白(CRP)、简化克罗恩病活动指数(CDAI)、克罗恩病改良乘数简化内镜评分(MM-SES-CD)等。采用多因素logistic回归分析筛选克罗恩病患者抗TNF-α单抗治疗中发生PNR的独立危险因素并构建列线图预测模型。通过比较受试者操作特征曲线(ROC)的曲线下面积(AUC),计算净重新分类指数(NRI)、综合判别改善指数(IDI),以及决策曲线分析(DCA)评估预测模型的预测效能和临床应用价值。统计学方法采用DeLong检验。结果多因素logistic回归分析显示,基线CRP较高[OR=1.030,95%置信区间(95%CI)1.002~1.059]、高简化CDAI(OR=1.399,95%CI 1.023~1.913)和高MM-SES-CD(OR=1.100,95%CI 1.025~1.181)为克罗恩病患者抗TNF-α单抗治疗中发生PNR的独立危险因素(P=0.033、0.036、0.008)。ROC分析显示,CRP、简化CDAI、MM-SES-CD、预测模型在建模组和验证组的AUC分别为0.697(95%CI 0.573~0.821)、0.772(95%CI 0.666~0.879)、0.819(95%CI 0.725~0.912)、0.869(95%CI 0.786~0.951)、0.856(95%CI 0.756~0.955),预测模型在建模组的AUC大于CRP和简化CDAI,差异均有统计学意义(Z=3.00、2.75,P=0.003、0.006),与MM-SES-CD和验证组比较,差异均无统计学意义(均P>0.05);但建模组预测模型相对MM-SES-CD的NRI与IDI分别为0.205(95%CI 0.002~0.409,P=0.048)和0.098(95%CI 0.022~0.174,P=0.011),提示预测模型的预测能力较MM-SES-CD更佳。DCA显示,预测模型在建模组和验证组中均有较大的临床获益。结论基于克罗恩病患者抗TNF-α单抗治疗中发生PNR的独立Objective To investigate the risk factors and establish a prediction model of primary non-response(PNR)to anti-tumor necrosis factor-α(TNF-α)monoclonal antibody in Crohn′s disease(CD)patients.Methods From December 1,2018 to July 31,2022,103 patients with CD treated with the anti-TNF-αmonoclonal antibody in Renmin Hospital of Wuhan University were enrolled(modeling group),and at the same time,109 patients with CD treated with anti-TNF-αmonoclonal antibody in Zhongnan Hospital of Wuhan University were selected(validation group).The baseline clinical data of all the patients before the first treatment of anti-TNF-αmonoclonal antibody were collected,which included C-reactive protein(CRP),the simplified Crohn′s disease activity index(CDAI),and modified multiplier simple endoscopic score for Crohn′s disease(MM-SES-CD),etc.Multivariate logistic regression was used to screen the independent risk factors of PNR in patients with CD treated with the anti-TNF-αmonoclonal antibody,and to establish the nomograms prediction model.The area under the curve(AUC)of the receiver operating characteristic curve(ROC),the net reclassification index(NRI),integrated discrimination improvement index(IDI),and decision curve analysis(DCA)were used to evaluate the predictive efficacy and clinical application value of the prediction model.DeLong test was used for statistical analysis.Results The results of multivariate logistic regression analysis showed that high level of CRP(OR=1.030,95%confidence interval(95%CI)1.002 to 1.059),simplified CDAI(OR=1.399,95%CI 1.023 to 1.913),and MM-SES-CD(OR=1.100,95%CI 1.025 to 1.181)in baseline were independent risk factors of PNR in patients with CD treated with the anti-TNF-αmonoclonal antibody(P=0.033,0.036 and 0.008).The results of ROC analysis showed that the AUCs of CRP,simplified CDAI,MM-SES-CD,and the prediction model in the modeling group and the validation group were 0.697(95%CI 0.573 to 0.821),0.772(95%CI 0.666 to 0.879),0.819(95%CI 0.725 to 0.912),0.869(95%CI 0.786 to 0.951)and 0.85

关 键 词：CROHN病 抗肿瘤坏死因子 原发性失应答 列线图 

分 类 号：R574[医药卫生—消化系统]