Tarabar Dino, Hirsch Ayal, Rubin David T
a Clinic for Gastroenterology and Hepatology , Military Medical Academy , Belgrade , Serbia.
b Department of Medicine , University of Chicago, Inflammatory Bowel Disease Center , Chicago , IL , USA.
Expert Rev Gastroenterol Hepatol. 2016;10(3):283-90. doi: 10.1586/17474124.2016.1135051. Epub 2016 Jan 25.
Vedolizumab, a recent addition to the therapeutic armamentarium in Crohn's disease, is promising in efficacy, durability of remission and safety. It is the first gut selective biologic treatment, acting by targeting α4β7-integrin, a receptor expressed on activated lymphocytes and binding to MAdCAM1, a cell adhesion molecule selectively expressed in the circulatory system of the digestive tract, preventing trafficking of lymphocytes to the gut. The pivotal GEMINI studies have demonstrated the efficacy and safety of vedolizumab in achieving clinical response and clinical remission in patients with moderately to severely active CD who are naïve or have previously failed therapy with TNF-antagonists, immunomodulators or dependent on steroids. Vedolizumab had a favorable safety profile and specifically showed no evidence of PML, reactivation of latent TB or hepatitis B. Overall, the number of malignancies in the clinical trials was small; however, long-term exposure was limited. Vedolizumab can be given as a first-line therapy or following treatment failure, and was tolerated as part of combination therapy. More medications with similar and novel therapeutic mechanisms are anticipated in the coming years.
维多珠单抗是近年来克罗恩病治疗药物库中的新成员,在疗效、缓解的持久性和安全性方面都很有前景。它是首个肠道选择性生物治疗药物,通过靶向α4β7整合素发挥作用,α4β7整合素是一种在活化淋巴细胞上表达的受体,可与黏膜地址素细胞黏附分子1(MAdCAM1)结合,MAdCAM1是一种在消化道循环系统中选择性表达的细胞黏附分子,可阻止淋巴细胞向肠道迁移。关键的GEMINI研究已经证明,维多珠单抗对于初治或先前使用肿瘤坏死因子拮抗剂、免疫调节剂治疗失败或依赖类固醇治疗的中度至重度活动性克罗恩病患者,在实现临床反应和临床缓解方面具有疗效和安全性。维多珠单抗具有良好的安全性,尤其未显示出进行性多灶性白质脑病、潜伏性结核或乙型肝炎再激活的证据。总体而言,临床试验中的恶性肿瘤病例数较少;然而,长期暴露情况有限。维多珠单抗可作为一线治疗药物,也可在治疗失败后使用,并且作为联合治疗的一部分也能被耐受。预计在未来几年会有更多具有相似和新颖治疗机制的药物出现。