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肿瘤坏死因子抑制剂在克罗恩病中的应用。

Use of the tumor necrosis factor-blockers for Crohn's disease.

机构信息

Division of Gastroenterology, Department of Medicine, University of Western Ontario, London, Canada.

出版信息

World J Gastroenterol. 2012 Sep 21;18(35):4823-54. doi: 10.3748/wjg.v18.i35.4823.

Abstract

The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1) for persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy, and when or if TNFB may be weaned and discontinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

摘要

抗肿瘤坏死因子-α 治疗在炎症性肠病的应用代表了自三十年前国家合作性克罗恩病研究发表以来这些患者治疗方面最重要的进展。现在,来自全球众多共识小组的建议得到了大量临床试验和几项荟萃分析的支持。一般来说,建议肿瘤坏死因子-α 阻滞剂(TNFB)适用于以下人群:(1)对两种或两种以上糖皮质激素治疗无效且接受过免疫调节剂(如硫唑嘌呤或甲氨蝶呤)治疗 8 至 12 周的中重度克罗恩病或溃疡性结肠炎患者;(2)对非甾体抗炎药治疗无效的肛周疾病;(3)对 3 至 5 天激素治疗无反应的重度溃疡性结肠炎。一旦引入 TNFB 且患者有反应,必须继续通过静脉注射和皮下注射给药。是否需要在 TNFB 维持治疗时同时使用免疫调节剂,以及何时或是否可以逐渐减少和停止 TNFB,仍需要明确的证据。关于 TNFB 在患者疾病过程中早期或晚期引入的作用的单中心研究的支持证据需要得到证实。只要在开始 TNFB 治疗前对患者进行免疫接种和结核及病毒性肝炎检测,并且长期对淋巴瘤和其他肿瘤的发展没有不良影响,TNFB 的风险/获益情况似乎是可以接受的。由于从人群角度来看,TNFB 的获益率适中,且治疗费用非常高,因此 TNFB 的最终应用可能取决于成本/效益研究。

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