Division of Gastroenterology, University of California, 9500 Gilman Dr, San Diego, La Jolla, CA, 92093, USA.
Robarts Clinical Trials Inc., 100 Dundas St., Suite 200, London, ON, N6A 5B6, Canada.
Drug Saf. 2019 May;42(5):617-632. doi: 10.1007/s40264-018-00783-1.
Vedolizumab, a humanized monoclonal antibody to the α4β7 integrin, reduces lymphocyte trafficking to the intestine. This gut-selective mechanism of action offers a safer alternative to other biologics used to treat ulcerative colitis (UC) and Crohn's disease (CD). We reviewed efficacy and safety data from randomized controlled trials (RCTs), open-label extension (OLE) and observational studies, and pooled analyses of vedolizumab therapy. In UC, RCTs demonstrate that vedolizumab is effective for induction and maintenance of remission, regardless of prior tumor necrosis factor (TNF) antagonist exposure. In CD, vedolizumab is moderately effective as an induction therapy and demonstrates efficacy as a maintenance agent. Secondary analyses indicate that prolonged induction therapy may result in greater efficacy, particularly in TNF antagonist-exposed patients. Comparative efficacy studies and network meta-analyses show similar efficacy to other biologic therapies. OLE studies in UC and CD demonstrate the durability of maintenance efficacy and low serious adverse event (SAE) rates. In an integrated safety analysis of controlled data, there was no significant difference in adverse event, SAE, infection and serious infection rates between vedolizumab and placebo. No drug-specific safety signals were identified. Immunogenicity rates were low and no cases of progressive multifocal leukoencephalopathy directly attributable to vedolizumab are reported in the literature. Vedolizumab is effective for induction and maintenance of inflammatory bowel disease with low treatment-related risks. Given the high therapeutic index of this gut-specific agent, it can be used as either a first- or second-line biologic therapy for UC and CD.
维得利珠单抗是一种针对 α4β7 整合素的人源化单克隆抗体,可减少淋巴细胞向肠道的迁移。这种肠道选择性作用机制为治疗溃疡性结肠炎 (UC) 和克罗恩病 (CD) 提供了比其他生物制剂更安全的选择。我们回顾了随机对照试验 (RCT)、开放标签扩展 (OLE) 和观察性研究以及维得利珠单抗治疗的汇总分析中的疗效和安全性数据。在 UC 中,RCT 表明,无论是否曾使用肿瘤坏死因子 (TNF) 拮抗剂,维得利珠单抗对诱导和维持缓解均有效。在 CD 中,维得利珠单抗作为诱导疗法具有中等疗效,并作为维持药物具有疗效。次要分析表明,延长诱导治疗可能会产生更大的疗效,尤其是在 TNF 拮抗剂暴露的患者中。比较疗效研究和网络荟萃分析表明,其疗效与其他生物疗法相似。UC 和 CD 的 OLE 研究表明维持疗效持久且严重不良事件 (SAE) 发生率低。在对照数据的综合安全性分析中,维得利珠单抗与安慰剂之间在不良事件、SAE、感染和严重感染发生率方面无显著差异。未发现药物特异性安全性信号。免疫原性发生率低,文献中未报告与维得利珠单抗直接相关的进行性多灶性白质脑病的病例。维得利珠单抗可有效诱导和维持炎症性肠病,治疗相关风险低。鉴于该肠道特异性药物的治疗指数高,可将其作为 UC 和 CD 的一线或二线生物治疗药物。