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在炎症性肠病的药物治疗方面,我们正朝着什么方向发展?

Where are we heading to in pharmacological IBD therapy?

作者信息

Rogler Gerhard

机构信息

Division of Gastroenterology & Hepatology, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

出版信息

Pharmacol Res. 2015 Oct;100:220-7. doi: 10.1016/j.phrs.2015.07.005. Epub 2015 Aug 12.

Abstract

After a relatively long time of failed developments and negative clinical trials in pharmacological inflammatory bowel disease (IBD) therapy we now phase a time of a great number of successful studies and new therapy principles that will most likely make it into clinical practice. This will change the landscape of IBD therapy in future markedly. Many new therapeutic principles have been developed and old ones that seemed to have failed such as anti-sense technology suddenly now provide promising results. Some initially promising therapies will need further development or have failed such as Trichuris suis ova therapy (but not helminth therapy in general), CCR9 targeted therapies or recombinant IL-10. In contrast anti-leukocate trafficking therapies appear to be quite promising. Vedolizumab is the first in class anti-integrin antibody that was approved for the therapy of CD and UC recently. Other anti-integrin antibodies and small molecule adhesion inhibitors will most likely be approved in the next years for IBD therapy. Tofacitinib, a small molecule JAK inhibitor, is a promising candidate for the treatment of UC. Phosphatidylcholine may be a future option for patients with 5-ASA refractory UC or 5-ASA intolerance. The preliminary data for Mongersen, a Smad7 antisense oligonucleotide, are promising despite some concerns about long term effect of TGFβ induction. Anti IL6 strategies will hopefully be further evaluated keeping in mind the caveat of a lack of CRP induction in anti-IL6 treated patients. Stem cell transplantation will become an option for patients that have experienced failure of established medications. Fecal microbiota transplantation and also perhaps combined probiotic therapy is a field that will be evaluated in more detail in the near future especially for UC patients. Based on these new developments treatment algorithms need to be updated. This review will reflect these current developments and give a perspective for future IBD therapy.

摘要

在药物性炎症性肠病(IBD)治疗经历了较长时间的研发失败和临床试验阴性结果之后,我们现在正处于一个大量成功研究和新治疗原则涌现的时期,这些研究和原则很可能会进入临床实践。这将在未来显著改变IBD治疗的格局。许多新的治疗原则已经被开发出来,一些看似失败的旧原则,如反义技术,现在突然产生了有前景的结果。一些最初有前景的疗法需要进一步研发或已经失败,如猪鞭虫卵疗法(但一般的蠕虫疗法并非如此)、CCR9靶向疗法或重组IL-10。相比之下,抗白细胞趋化疗法似乎很有前景。维多珠单抗是首个获批用于治疗克罗恩病(CD)和溃疡性结肠炎(UC)的抗整合素抗体。其他抗整合素抗体和小分子黏附抑制剂很可能在未来几年获批用于IBD治疗。托法替布,一种小分子JAK抑制剂,是治疗UC的有前景的候选药物。磷脂酰胆碱可能是5-氨基水杨酸(5-ASA)难治性UC或5-ASA不耐受患者的未来选择。尽管对Smad7反义寡核苷酸蒙格森的长期效应存在一些担忧,但其初步数据很有前景。抗IL6策略有望得到进一步评估,同时要注意抗IL6治疗患者缺乏C反应蛋白(CRP)诱导这一问题。干细胞移植将成为那些现有药物治疗失败患者的一种选择。粪便微生物群移植以及可能的联合益生菌疗法是一个在不久的将来将得到更详细评估的领域,特别是对于UC患者。基于这些新进展,治疗算法需要更新。本综述将反映这些当前的进展,并为未来的IBD治疗提供一个展望。

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