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原发性克罗恩病患者对 TNF 治疗无反应的凋亡和炎症基因变异。

Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn's disease patients.

机构信息

Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences.

Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.

出版信息

Eur J Gastroenterol Hepatol. 2023 Oct 1;35(10):1088-1096. doi: 10.1097/MEG.0000000000002618. Epub 2023 Jul 31.

Abstract

Anti-TNF therapy has indeed revolutionized the treatment of Crohn's disease, leading to higher rates of response and remission in patients. However, a significant proportion of 20-40% of patients do not respond to the initial therapy, others experience a secondary loss of response with ongoing treatment. Adverse drug reactions also occur in some patients. The effectiveness of anti-TNF treatment may be influenced by genetic variability, including FCGR3A, ADAM17, TNFRSF1A, TNFRSF1B, FAS, FASL, IL1B, CASP9 , and MIF genes. In this article, we provide an overview of the current knowledge and findings in the pharmacogenetics of anti-TNF drugs in CD focusing on the aspect of apoptosis and inflammatory genes variants in primary non-response. Pharmacogenetic investigations have been conducted to identify genetic markers that can predict response to anti-TNF therapy. However, large multi-center validation studies and multi-loci algorithms development are required to effectively prognose the treatment effect. The identification of predictive markers of response to anti-TNF therapy can help clinicians make informed decisions about treatment options and minimize adverse drug reactions in patients.

摘要

抗 TNF 治疗确实改变了克罗恩病的治疗方式,使患者的应答率和缓解率更高。然而,仍有 20-40%的患者对初始治疗无应答,另有部分患者在持续治疗中出现应答丧失。一些患者也会出现药物不良反应。抗 TNF 治疗的有效性可能受到遗传变异性的影响,包括 FCGR3A、ADAM17、TNFRSF1A、TNFRSF1B、FAS、FASL、IL1B、CASP9 和 MIF 基因。本文就 CD 中抗 TNF 药物的药物遗传学概述提供了当前知识和研究结果,重点介绍原发性无应答中凋亡和炎症基因变异方面的内容。已经开展了药物遗传学研究以确定可以预测抗 TNF 治疗应答的遗传标志物。然而,需要进行大型多中心验证研究和多基因座算法开发,以有效预测治疗效果。识别抗 TNF 治疗应答的预测标志物可以帮助临床医生针对治疗方案做出明智决策,并最大程度减少患者的药物不良反应。

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