药物遗传学在类风湿关节炎和克罗恩病抗TNF治疗中的潜在作用。
Potential role of pharmacogenetics in anti-TNF treatment of rheumatoid arthritis and Crohn's disease.
作者信息
Kooloos Wouter M, de Jong Dirk J, Huizinga Tom W J, Guchelaar Henk-Jan
机构信息
Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, PO Box 9600, NL 2300 RC Leiden, The Netherlands.
出版信息
Drug Discov Today. 2007 Feb;12(3-4):125-31. doi: 10.1016/j.drudis.2006.11.013. Epub 2006 Dec 4.
Etanercept, infliximab and adalimumab have shown clinical benefit in immune-mediated inflammatory diseases; however, the outcome of treatment with these tumour-necrosis factor inhibitors remains insufficient in approximately 40-60% and approximately 25-40% of individuals with rheumatoid arthritis and Crohn's disease, respectively. Moreover, their use is accompanied by adverse events and unintentional immune suppression. Pharmacogenetics has the potential to increase efficacy and ameliorate adverse events and immune suppression, and its application might be of clinical benefit for patients with rheumatoid arthritis and Crohn's disease. Pharmacogenetic studies have shown associations between single nucleotide polymorphisms in genes encoding enzymes related to the pharmacodynamics of these drugs and treatment outcome. As we discuss here, replication and prospective validation are warranted before pharmacogenetics can be used in clinical practice.
依那西普、英夫利昔单抗和阿达木单抗已在免疫介导的炎症性疾病中显示出临床益处；然而，在类风湿性关节炎患者中，约40%-60%使用这些肿瘤坏死因子抑制剂治疗的结果仍然不尽人意，在克罗恩病患者中这一比例约为25%-40%。此外，使用这些药物会伴随不良事件和无意的免疫抑制。药物遗传学有潜力提高疗效、改善不良事件和免疫抑制，其应用可能对类风湿性关节炎和克罗恩病患者具有临床益处。药物遗传学研究表明，编码与这些药物药效学相关酶的基因中的单核苷酸多态性与治疗结果之间存在关联。正如我们在此所讨论的，在药物遗传学能够应用于临床实践之前，有必要进行重复研究和前瞻性验证。
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