Seo Geom Seog, Lee Sung Hee
Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Korea.
Institute of Pharmaceutical Research and Development, Wonkwang University College of Pharmacy, Iksan, Korea.
Korean J Gastroenterol. 2018 Feb 25;71(2):81-88. doi: 10.4166/kjg.2018.71.2.81.
The treatment of inflammatory bowel disease has evolved with the development of anti-TNF agents. In spite of long-term effectiveness, many patients do not respond or no longer responds to these drugs. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. Vedolizumab, a gut-specific biological agent, inhibits interaction α4β7 integrin with mucosal addressin cell adhesion molecule-1 without inhibiting systemic immune responses. Long-term vedolizumab therapy in patients with Crohn's disease and ulcerative colitis was safe and effective. Additionally, vedolizumab can be used in patients already failed an anti-TNF therapy. Ustekinumab is a fully human immunoglobulin G1 kappa monoclonal antibody that blocks the p40 subunit of IL-12 and IL-23. Ustekinumab will be a clinically effective agent to use in medically-refractory Crohn's disease especially as a second line drug. Tofacitinib is an oral, small molecule that inhibits JAK1, JAK3 and in a lesser extent, JAK2. Perhaps the most attractive things of these JAK inhibitors is that they are given orally instead of parenterally. Early results showed that patients with moderately to severely active ulcerative colitis receiving tofacitinib were more likely to achieve remission at 8 weeks than those receiving placebo. However, these results have not been as robust in Crohn's disease. Much of the positioning will depend on the safety profile such as opportunistic infection and atherogenic risk. The challenges for the future are to determine the therapeutic drug monitoring-guided dose optimization, optimal timing and drug combinations to produce the most effective, and safest outcomes for IBD patients.
随着抗TNF药物的发展，炎症性肠病的治疗也在不断演变。尽管这些药物具有长期疗效，但许多患者对其无反应或不再有反应。因此，开发作用于不同炎症途径的新药变得十分必要。维多珠单抗是一种肠道特异性生物制剂，可抑制α4β7整合素与黏膜地址素细胞黏附分子-1的相互作用，而不抑制全身免疫反应。对克罗恩病和溃疡性结肠炎患者进行长期维多珠单抗治疗是安全有效的。此外，维多珠单抗可用于抗TNF治疗失败的患者。乌司奴单抗是一种全人源免疫球蛋白G1κ单克隆抗体，可阻断IL-12和IL-23的p40亚基。乌司奴单抗将成为治疗难治性克罗恩病的临床有效药物，尤其是作为二线药物。托法替布是一种口服小分子药物，可抑制JAK1、JAK3，在较小程度上还可抑制JAK2。这些JAK抑制剂最吸引人的地方或许在于它们是口服给药而非胃肠外给药。早期结果显示，中度至重度活动性溃疡性结肠炎患者接受托法替布治疗8周时达到缓解的可能性高于接受安慰剂治疗的患者。然而，在克罗恩病中这些结果并不那么显著。很大程度上，药物定位将取决于安全性，如机会性感染和动脉粥样硬化风险。未来的挑战在于确定治疗药物监测指导下的剂量优化、最佳用药时机和药物组合，以为炎症性肠病患者带来最有效且最安全的治疗效果。
