{"title":"开发并验证基于治疗药物监测的新型提名图，用于预测活动性克罗恩病抗 TNF 治疗的初级内镜反应。","authors":"Liang Chen, Dengfeng Kang, Leilei Fang, Mingming Sun, Mingsong Li, Guangxi Zhou, Chunjin Xu, Zhi Pang, Yulan Ye, Baisui Feng, Huili Wu, Jian Lin, Baijing Ding, Changqin Liu, Yanhong Shi, Zhanju Liu","doi":"10.1177/17562848241256237","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (<i>p</i> < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (<i>p</i> < 0.001), CDAI (<i>p</i> < 0.001), and C-reactive protein (CRP) (<i>p</i> < 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143805/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.\",\"authors\":\"Liang Chen, Dengfeng Kang, Leilei Fang, Mingming Sun, Mingsong Li, Guangxi Zhou, Chunjin Xu, Zhi Pang, Yulan Ye, Baisui Feng, Huili Wu, Jian Lin, Baijing Ding, Changqin Liu, Yanhong Shi, Zhanju Liu\",\"doi\":\"10.1177/17562848241256237\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.</p><p><strong>Design: </strong>Cross-sectional study.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (<i>p</i> < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (<i>p</i> < 0.001), CDAI (<i>p</i> < 0.001), and C-reactive protein (CRP) (<i>p</i> < 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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":48770,\"journal\":{\"name\":\"Therapeutic Advances in Gastroenterology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-05-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143805/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Advances in Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17562848241256237\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562848241256237","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：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，血清抗肿瘤坏死因子治疗药物监测（TDM）在监测炎症性肠病（IBD）治疗中的预测作用仍存在争议：使用基于TDM的提名图，探讨血清抗TNF水平与活动性CD早期内镜反应之间的相关性：设计：横断面研究：方法：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 的血清谷值水平：结果：在研究队列中，内镜反应患者的 IFX 或 ADA 谷值水平明显高于非反应患者（p p p p 结论：该研究表明，内镜反应与 IFX 或 ADA 谷值水平之间存在密切联系：这项研究表明，活动性 CD 患者血清中 IFX、ADA、Alb 和 CRP 的浓度与原发性内镜反应之间存在密切联系。重要的是，基于 TDM 和实验室标记物的提名图可用来评估抗肿瘤坏死因子治疗的原发性内镜反应，尤其是用于 CD 患者的治疗策略优化和治疗转换。
Development and validation of a novel therapeutic drug monitoring-based nomogram for prediction of primary endoscopic response to anti-TNF therapy in active Crohn's disease.
Background: 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.
Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram.
Design: Cross-sectional study.
Methods: 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.
Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort (p < 0.001). The IFX and ADA levels showed a weak but significantly negative correlation with SES-CD (p < 0.001), CDAI (p < 0.001), and C-reactive protein (CRP) (p < 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.
Conclusion: 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.
期刊介绍：
Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area.
The editors welcome original research articles across all areas of gastroenterology and hepatology.
The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.
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