The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with anti-tumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation. The latter issues necessitate the use of medications with different mechanisms of action. Besides the biologics natalizumab, vedolizumab and ustekinumab that have already been approved for the treatment of IBD new non-anti-TNF therapies are currently under investigation including small molecule drugs against Janus kinase and sphingosine-1-phosphate receptors. This manuscript will review the medications that are in the later stages of development for the treatment of IBD and directed against immune targets other than TNF.

中文翻译：

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炎性肠病的生物疗法：超越抗TNF疗法。

在过去的二十年中，炎症性肠病（IBD）的药理学管理已从对氨基水杨酸盐​​，皮质类固醇和免疫调节剂的依赖过渡到早期抗肿瘤坏死因子（TNF）治疗。尽管如此，仍有20-30％的患者在一年内因原发性无反应而终止抗TNF治疗，另有30-40％的患者因失去反应而中止反应。这些不良的治疗结果可归因于以非TNF驱动的炎症为特征的药代动力学（抗药物抗体和/或低药物浓度）或药效学问题。后者的问题使得必须使用具有不同作用机理的药物。除了那他珠单抗的生物制剂，已经被批准用于治疗IBD的新的非抗TNF治疗药物vedolizumab和ustekinumab目前正在研究中，包括针对Janus激酶和1鞘氨醇鞘氨醇受体的小分子药物。该手稿将回顾在治疗IBD的后期阶段中针对TNF以外的免疫靶点的药物。