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硫嘌呤类药物:近期研究热点及其在炎症性肠病治疗中的作用

Thiopurines: Recent Topics and Their Role in the Treatment of Inflammatory Bowel Diseases.

作者信息

Tominaga Keiichi, Sugaya Takeshi, Tanaka Takanao, Kanazawa Mimari, Iijima Makoto, Irisawa Atsushi

机构信息

Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan.

出版信息

Front Pharmacol. 2021 Jan 29;11:582291. doi: 10.3389/fphar.2020.582291. eCollection 2020.

Abstract

Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory bowel diseases (IBD) of unknown etiology, characterized by repeated relapse and remission. The efficacy of thiopurine in IBD was first reported in the late 1960s. Thiopurines are used to alleviate the symptoms of IBD, especially UC. These drugs have a steroid-sparing potential and are widely used for the purpose of maintaining long-term remission in steroid-dependent cases. Therefore, thiopurines tend to be used long-term, but adverse events that accompany long-term use, such as lymphoproliferative disorders, must be monitored with care. In contrast, thiopurine plays a critical role in controlling the immunogenicity of biologics. Furthermore, although thiopurine is an old drug, new findings, including the prediction of serious adverse events such as severe alopecia and acute advanced leukopenia, by nudix hydrolase 15 gene polymorphism analysis, as well as the possibility of appropriate drug monitoring by detailed analysis of 6-thioguanine nucleotides have been clarified. However, the consequences of thiopurine withdrawal have not been determined and further studies, including randomized controlled trials, are necessary to answer the clinical question regarding the scenarios in which thiopurine withdrawal is possible.

摘要

溃疡性结肠炎(UC)和克罗恩病(CD)是病因不明的慢性炎症性肠病(IBD),其特征为反复复发和缓解。硫唑嘌呤在IBD中的疗效最早于20世纪60年代末被报道。硫唑嘌呤用于缓解IBD的症状,尤其是UC。这些药物具有节省类固醇的潜力,被广泛用于维持类固醇依赖型病例的长期缓解。因此,硫唑嘌呤往往长期使用,但必须密切监测长期使用伴随的不良事件,如淋巴增殖性疾病。相比之下,硫唑嘌呤在控制生物制剂的免疫原性方面起着关键作用。此外,尽管硫唑嘌呤是一种老药,但通过nudix水解酶15基因多态性分析预测严重不良事件(如严重脱发和急性进展性白细胞减少)以及通过详细分析6-硫鸟嘌呤核苷酸进行适当药物监测的新发现已经明确。然而,硫唑嘌呤停药的后果尚未确定,需要进一步研究,包括随机对照试验,以回答关于硫唑嘌呤停药可能情况的临床问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d60/7878672/87a7ee904237/fphar-11-582291-g001.jpg

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