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综述文章:服用免疫调节剂的炎症性肠病患者的实际管理

Review article: practical management of inflammatory bowel disease patients taking immunomodulators.

作者信息

Siegel C A, Sands B E

机构信息

Gastrointestinal Unit and MGH Crohn's and Colitis Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

出版信息

Aliment Pharmacol Ther. 2005 Jul 1;22(1):1-16. doi: 10.1111/j.1365-2036.2005.02520.x.

Abstract

Azathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity. This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the purine antagonists--azathioprine and mercaptopurine--the evidence for utility of thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitors--ciclosporin and tacrolimus--can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations.

摘要

硫唑嘌呤、巯嘌呤、甲氨蝶呤、环孢素和他克莫司在炎症性肠病的治疗中都有各自的适用范围。这些免疫调节剂是强效且有效的药物;然而,它们可能具有严重的毒性。为了使益处最大化并将风险最小化,临床医生必须了解这些药物的作用机制、适用指征、毒性范围和正确剂量。此外,一旦开始治疗,就需要对患者进行适当监测,以获取疗效和毒性的证据。本综述包括使用免疫调节剂管理和监测患者的推荐背后的基本原理。对于嘌呤拮抗剂——硫唑嘌呤和巯嘌呤——阐述了硫嘌呤甲基转移酶检测和巯嘌呤代谢物监测效用的证据。回顾了肝活检以及对服用甲氨蝶呤患者进行亚甲基四氢叶酸还原酶突变筛查的作用。通过适当监测,钙调神经磷酸酶抑制剂——环孢素和他克莫司——可以安全有效地使用。免疫调节剂是治疗克罗恩病和溃疡性结肠炎的重要药物,开处方的临床医生应能充分认识到它们的价值和局限性。

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