Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
IBD Service, Department of Gastroenterology, The Queen Elizabeth Hospital, Woodville South, Adelaide, South Australia, 5011, Australia.
Best Pract Res Clin Gastroenterol. 2019 Feb-Apr;38-39:101617. doi: 10.1016/j.bpg.2019.05.004. Epub 2019 May 28.
The discovery of gut-specific leukocytes and the ability to modulate their function has been a groundbreaking development in the treatment of inflammatory bowel disease. Drugs target the interaction between lymphocytes and endothelial cells via integrins and their ligand cellular adhesion molecules. Safety, efficacy and sustainability of effect are key to this drug class, notwithstanding the association of natalizumab with fatal polyoma virus infection. Vedolizumab (2014) now licensed for the treatment of Crohn's disease around the world provides gut-specific immunosuppression. Targets for modulators of leukocyte trafficking include (examples in brackets) ICAM-1 (alicaforsen, efalizumab); MAdCAM-1 (PF-00547 659); α4 and related receptors (abrilumab, etrolizumab, natalizumab, vedolizumab); chemokine receptor CCR9 (vercirnon); and sphingosine 1-phosphate receptors (etrasimod, fingolimod, ozanimod). Oral and subcutaneous therapies are in development. The safety, efficacy and practice points of licensed drugs are discussed, in addition to initial results from therapeutic trials.
肠道特异性白细胞的发现及其功能的调节能力是治疗炎症性肠病的突破性进展。药物通过整合素及其配体细胞黏附分子靶向淋巴细胞与内皮细胞的相互作用。尽管与纳武单抗相关的致命多瘤病毒感染有关，但该药物类别的安全性、疗效和效果的可持续性仍然是关键。维得利珠单抗（vedolizumab，2014 年）现已在全球范围内获得批准用于治疗克罗恩病，为肠道提供特异性免疫抑制作用。白细胞迁移调节剂的靶点包括（括号内举例）ICAM-1（阿利昔单抗、efalizumab）；MAdCAM-1（PF-00547659）；α4 及其相关受体（阿柏西普、依特立珠单抗、那他珠单抗、维得利珠单抗）；趋化因子受体 CCR9（vercirnon）；和鞘氨醇 1-磷酸受体（依特司莫单抗、芬戈莫德、奥扎尼莫德）。口服和皮下治疗正在开发中。本文除了讨论已获许可药物的安全性、疗效和实践要点外，还介绍了治疗试验的初步结果。
