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[慢性炎症性肠病中的生物疗法]

[Biologic therapies in chronic inflammatory bowel diseases].

作者信息

Reenaers C, Louis E, Belaiche J

机构信息

Université de Liège, CHU de Liège, Belgique.

出版信息

Rev Med Liege. 2009 May-Jun;64(5-6):301-4.

Abstract

Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases which can be difficult to control with conventional therapies. Thanks to a better knowledge of their physiopathology, new therapies aimed at specific targets of the inflammatory cascade were developed. Three monoclonal anti-TNF antibodies were produced. Infliximab and adalimumab, currently widely used, can induce sustained remission in Crohn's disease. Infliximab is also efficacious in UC. Certolizumab pegol provides good short term results; its long term efficacy, however, remains to be assessed by further clinical trials. Therapies targeting leucocyte trafficking (anti-integrine) have also been provided and are associated with good clinical responses in Crohn's disease. Natalizumab (anti-alpha4) is responsible for significant side effects and is no longer in use in gasrtoenterology in Europe whereas MLN02 (anti-alpha417) has a good profile in terms of efficacy and safety. Monoclonal anti bodies targeting other cytokines are under development, mainly ustekinumab which inhibits IL12 and IL23. Ustekinumab generates favourable clinical responses in Crohn's disease. The development of biologic therapies in inflammatory bowel disease has dramatically altered the course and management of these disorders.

摘要

克罗恩病和溃疡性结肠炎是慢性炎症性肠病,传统疗法难以对其进行控制。由于对其生理病理学有了更深入的了解,针对炎症级联反应特定靶点的新疗法得以研发。已生产出三种单克隆抗TNF抗体。目前广泛使用的英夫利昔单抗和阿达木单抗可诱导克罗恩病持续缓解。英夫利昔单抗对溃疡性结肠炎也有效。赛妥珠单抗短期效果良好;然而,其长期疗效仍有待进一步临床试验评估。针对白细胞迁移(抗整合素)的疗法也已出现,且在克罗恩病中与良好的临床反应相关。那他珠单抗(抗α4)会引发严重副作用,在欧洲已不再用于胃肠病学领域,而MLN02(抗α4β7)在疗效和安全性方面表现良好。针对其他细胞因子的单克隆抗体正在研发中,主要是抑制IL12和IL23的优特克单抗。优特克单抗在克罗恩病中产生了良好的临床反应。炎症性肠病生物疗法的发展极大地改变了这些疾病的病程和治疗方式。

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