Chen Liang, Kang Dengfeng, Fang Leilei, Sun Mingming, Li Mingsong, Zhou Guangxi, Xu Chunjin, Pang Zhi, Ye Yulan, Feng Baisui, Wu Huili, Lin Jian, Ding Baijing, Liu Changqin, Shi Yanhong, Liu Zhanju
Department of Gastroenterology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Therap Adv Gastroenterol. 2024 May 30;17:17562848241256237. doi: 10.1177/17562848241256237. eCollection 2024.
Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn's disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial.
To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.
Cross-sectional study.
The simplified endoscopic activity score for CD (SES-CD), Crohn's disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed.
The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort ( < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD ( < 0.001), CDAI ( < 0.001), and C-reactive protein (CRP) ( < 0.001) at week 14 post-IFX therapy in the development cohort. Furthermore, the receiver operating characteristic curve revealed that an optimal level of IFX (4.80 μg/mL) and ADA (8.80 μg/mL) exhibited the best performance in predicting endoscopic response. Concomitantly, we developed a novel nomogram prediction model based on the results of multivariate logistic regression analysis, which consisted of CRP, albumin (Alb), and anti-TNF trough levels at week 14. The nomogram showed significant discrimination and calibration for both IFX and ADA in the development cohort and performed well in the external validation cohort.
This study demonstrates a robust association between serum concentrations of IFX, ADA, Alb, and CRP and primary endoscopic response in active CD patients. Importantly, the TDM- and laboratory marker-based nomogram may be used to evaluate the primary endoscopic response to anti-TNF therapy, especially for optimizing treatment strategies and switching therapy in CD patients.
抗肿瘤坏死因子（TNF）单克隆抗体，尤其是英夫利昔单抗（IFX）和阿达木单抗（ADA），被认为是活动性克罗恩病（CD）的一线治疗药物。然而，血清抗TNF治疗药物监测（TDM）在炎症性肠病（IBD）治疗监测中的预测作用仍存在争议。
使用基于TDM的列线图探讨活动性CD患者血清抗TNF水平与早期内镜反应之间的相关性。
横断面研究。
评估CD的简化内镜活动评分（SES-CD）、克罗恩病活动指数（CDAI）、实验室参数以及IFX和ADA的血清谷浓度。
在开发队列中，内镜反应患者的IFX或ADA谷浓度显著高于无反应者（<0.001）。在开发队列中，IFX和ADA水平在IFX治疗后第14周与SES-CD（<0.001）、CDAI（<0.001）和C反应蛋白（CRP）（<0.001）呈弱但显著的负相关。此外，受试者工作特征曲线显示，IFX的最佳水平（4.80μg/mL）和ADA的最佳水平（8.80μg/mL）在预测内镜反应方面表现最佳。同时，我们基于多因素逻辑回归分析结果开发了一种新型列线图预测模型，该模型由第14周的CRP、白蛋白（Alb）和抗TNF谷浓度组成。该列线图在开发队列中对IFX和ADA均显示出显著的区分度和校准度，并且在外部验证队列中表现良好。
本研究表明，活动性CD患者血清中IFX、ADA、Alb和CRP的浓度与主要内镜反应之间存在密切关联。重要的是，基于TDM和实验室标志物的列线图可用于评估抗TNF治疗的主要内镜反应，特别是用于优化CD患者的治疗策略和转换治疗方案。
