Predictors of Immunogenicity and Loss of Response to ANTI-TNFα Therapy in Crohn Disease-A Systematic Review.

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Simona Grad, Radu A Farcas, Dan L Dumitrascu, Teodora Surdea-Blaga, Abdulrahman Ismaiel, Stefan Popa
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Abstract

Background: As the use of anti-tumor necrosis factor-α (TNFα) therapies in Crohn disease (CD) is spread, the loss-of-response (LOR) to it is increasingly encountered. Discovering a pathological pathway and biomarkers that can predict LOR would assist in the management of patients with CD. In this article, we provide a comprehensive systematic review of studies assessing predictors of immunogenicity and loss-of-response to anti-TNFα drugs in patients with CD.

Data sources: We performed a systematic review of PubMed to identify citations pertaining to predictors of immunogenicity and loss-of-response to anti-TNFα drugs in patients with CD through April 27, 2024, using a predefined string of keywords. Data extraction and quality assessment were performed independently by 2 reviewers.

Results: A total of 18 eligible studies were included in the review. Four major groups of studies were identified: genetic factors, factors linked with colonic inflammation, serum and anthropological markers, and prevention of LOR. Promising predictors of LOR to infliximab or adalimumab include the carriage of HLA-DQA1*05, visceral adiposity, intestinal abundant presence of CD96, IL-17, and IL-23. Substantial heterogeneity was observed, and none of the markers had undergone formal validation. Specific limitations to acceptance of these factors included failure to use a standardized definition of LOR to anti-TNFα treatment, lack of specificity, and insufficient relevance to the pathogenesis of LOR.

Conclusions: This review underlines the lack of well-defined studies and controlled trials investigating predictors of LOR to anti-TNFα therapies in CD. A research priority is the development of reliable and accurate biomarkers that can shed light on the pathogenesis of the implied LOR. These biomarkers, along with genetic factors, have the potential to enhance clinical management by aiding in patient stratification and monitoring.

克罗恩病免疫原性和抗tnf α治疗反应丧失的预测因素——系统综述
背景:随着抗肿瘤坏死因子-α (tnf -α)治疗在克罗恩病(CD)中的应用的扩大,越来越多地遇到了对它的反应丧失(LOR)。发现一种可以预测LOR的病理途径和生物标志物将有助于CD患者的管理。在本文中,我们提供了一项全面的系统综述,评估CD患者免疫原性和抗tnf α药物反应丧失的预测因素。我们对PubMed进行了系统回顾,以确定到2024年4月27日为止与CD患者抗tnf α药物免疫原性和反应丧失预测因子相关的引文,使用预定义的关键词字符串。数据提取和质量评估由2名审稿人独立完成。结果:共纳入18项符合条件的研究。确定了四大类研究:遗传因素,与结肠炎症相关的因素,血清和人类学标记物,以及LOR的预防。对英夫利昔单抗或阿达木单抗有希望的预测因素包括HLA-DQA1*05的携带、内脏肥胖、肠道中CD96、IL-17和IL-23的丰富存在。观察到实质性的异质性,并且没有任何标记物经过正式验证。接受这些因素的具体限制包括:对抗tnf α治疗未能使用LOR的标准化定义,缺乏特异性,以及与LOR发病机制的相关性不足。结论:这篇综述强调了缺乏明确的研究和对照试验来研究抗tnf α治疗在CD中的LOR的预测因素。研究的重点是开发可靠和准确的生物标志物,可以揭示隐含的LOR的发病机制。这些生物标志物,连同遗传因素,有可能通过帮助患者分层和监测来加强临床管理。
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来源期刊
American journal of therapeutics
American journal of therapeutics PHARMACOLOGY & PHARMACY-
CiteScore
5.50
自引率
9.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: American Journal of Therapeutics is an indispensable resource for all prescribing physicians who want to access pharmacological developments in cardiology, infectious disease, oncology, anesthesiology, nephrology, toxicology, and psychotropics without having to sift through stacks of medical journals. The journal features original articles on the latest therapeutic approaches as well as critical articles on the drug approval process and therapeutic reviews covering pharmacokinetics, regulatory affairs, pediatric clinical pharmacology, hypertension, metabolism, and drug delivery systems.
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