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世界胃肠病学大会与欧洲克罗恩病和结肠炎组织关于 IBD 的生物治疗的伦敦立场声明:何时开始,何时停止,选择哪种药物,以及如何预测应答?

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

机构信息

Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands.

出版信息

Am J Gastroenterol. 2011 Feb;106(2):199-212; quiz 213. doi: 10.1038/ajg.2010.392. Epub 2010 Nov 2.

Abstract

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

摘要

生物疗法的出现彻底改变了炎症性肠病(IBD)的治疗模式。然而,并非所有患者都需要生物治疗。患者的选择取决于临床特征、先前对其他医学治疗的反应以及合并症。生物治疗的一线选择取决于可用性、报销指南和患者偏好,用于治疗腔型克罗恩病(CD)。英夫利昔单抗(IFX)拥有最广泛的临床试验数据,但其他生物制剂(阿达木单抗(ADA)、certolizumab pegol(CZP)和那他珠单抗(NAT))在 CD 中的疗效似乎相似。对于需要起始生物治疗的患者,需要满足以下条件:类固醇难治性、类固醇依赖性或复杂瘘管型 CD,在进行任何感染灶的外科引流后。对于瘘管型 CD,IFX 诱导瘘管闭合的疗效有最佳的证据支持。NAT 具有独特的风险,这使其在某些国家被归类为二线生物制剂。对诱导治疗有反应的患者从系统性再治疗中获益。IFX 联合硫唑嘌呤用于诱导缓解和黏膜愈合的效果优于单药治疗,在两种药物均未使用的患者中,1 年内缓解和黏膜愈合的效果更佳。但这种效果是否适用于其他药物尚不清楚。IFX 也可用于治疗难治性、中度或重度活动期溃疡性结肠炎。对于抗肿瘤坏死因子(TNF)治疗应答降低或丧失的患者,可能需要调整相同药物的剂量或转换为另一种药物。应仔细考虑丧失应答的原因。目前缺乏足够的数据来推荐何时停止抗 TNF 治疗。初步证据表明,在临床缓解>1 年且无明显炎症活动迹象的患者中,相当一部分患者在停止治疗后可维持缓解状态。

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