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首页> 外文期刊>Therapeutic advances in gastroenterology. >Emerging oral targeted therapies in inflammatory bowel diseases: opportunities and challenges
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Emerging oral targeted therapies in inflammatory bowel diseases: opportunities and challenges

机译：炎症性肠疾病中的新兴口服靶向疗法：机遇与挑战

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To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn’s disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins. In summary, until now the disease activity is not sufficiently controlled in a relevant fraction of the patients with IBD. Thus, there is an urge for the development of new substances in the therapy of ulcerative colitis and Crohn’s disease. Fortunately, new oral and parenteral substances are in the pipeline. This review will focus on oral substances, which have already passed phase II studies successfully at this stage. In this article, we summarize data regarding AJM300, phosphatidylcholine (LT-02), mongersen, ozanimod, filgotinib and tofacitinib. AJM300 and ozanimod were tested in patients with ulcerative colitis and target lymphocyte trafficking through inhibition of the α subunit of integrin, respectively binding to the sphingosine-1-phosphate receptor (subtypes 1 and 5) on lymphocytes. Mongersen was utilized in patients with Crohn’s disease and accelerates the degradation of SMAD7 mRNA, which consequently strengthens the mainly anti-inflammatory signalling pathway of transforming growth factor β1. Various Janus kinase (JAK) inhibitors were developed, which inhibit the intracellular signalling pathway of cytokines. For example, the JAK1 blocker filgotinib was tested in Crohn’s disease, whereas the JAK1/3 inhibitor tofacitinib was tested in clinical trials for both Crohn’s disease and ulcerative colitis. A different therapeutic approach is the substitution of phosphatidylcholine (LT-02), which might recover the colonic mucus. Taken together, clinical trials with these new agents have opened avenues for further clinical studies and it can be expected that at least some of these agents will be finally approved for clinical therapy.
机译：为了改善炎症性肠病（IBD：克罗恩氏病，溃疡性结肠炎）患者的生活质量并防止长期危险，必须充分抑制炎症活动。但是，皮质类固醇仅适用于急性耀斑的治疗，而诸如硫唑嘌呤或6-巯基丙氨酸之类的免疫抑制物质的积极作用的证据主要限于维持缓解。另外，仅患者亚组受益于靶向肿瘤坏死因子α或α4β7整联蛋白的生物制剂。总之，到目前为止，在IBD患者的相关部分中，疾病活动还没有得到充分控制。因此，迫切需要开发新的物质来治疗溃疡性结肠炎和克罗恩氏病。幸运的是，新的口服和非肠道药物正在准备中。这篇综述将集中在口服药物上，这些药物已经在现阶段成功通过了II期研究。在本文中，我们总结了有关AJM300，磷脂酰胆碱（LT-02），蒙格森，ozanimod，filgotinib和tofacitinib的数据。通过抑制整联蛋白的α亚基并分别结合淋巴细胞上的鞘氨醇-1-磷酸受体（亚型1和5），在溃疡性结肠炎和目标淋巴细胞运输的患者中测试了AJM300和奥扎尼莫德。 Mongersen被用于克罗恩病患者，并加速了SMAD7 mRNA的降解，从而增强了转化生长因子β1的主要抗炎信号通路。已经开发了多种Janus激酶（JAK）抑制剂，其抑制细胞因子的细胞内信号传导途径。例如，在克罗恩氏病中测试了JAK1阻断剂filgotinib，而在克罗恩氏病和溃疡性结肠炎的临床试验中测试了JAK1 / 3抑制剂托法替尼。另一种治疗方法是取代磷脂酰胆碱（LT-02），这可能会恢复结肠粘液。综上所述，使用这些新药物的临床试验为进一步的临床研究开辟了道路，可以预期，至少其中一些药物最终将被批准用于临床治疗。

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