Virginia Commonwealth University Health System, Richmond, VA, USA.
Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
Ther Adv Chronic Dis. 2015 Sep;6(5):224-33. doi: 10.1177/2040622315586970.
Ulcerative colitis (UC) and Crohn's disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted.
溃疡性结肠炎（UC）和克罗恩病（CD）是慢性、复发性炎症性肠病，与显著的发病率相关。这些疾病的传统治疗方法包括皮质类固醇、氨基水杨酸盐、免疫调节剂和单克隆抗体。多年来，肿瘤坏死因子（TNF）-α 拮抗剂单独或联合其他疗法已成为诱导和维持中度至重度 UC 和 CD 缓解的治疗基石。不幸的是，一些中度至重度 UC 和 CD 患者无法通过 TNF-α 拮抗剂治疗获得或维持缓解。维得利珠单抗是一种人源化单克隆抗体，是第一个获批的整合素受体拮抗剂，可选择性拮抗α4β7 胃肠道整合素受体。美国食品和药物管理局（FDA）批准用于治疗对 TNF-α 拮抗剂或免疫调节剂应答不足、应答丧失或不耐受；或对皮质类固醇应答不足、不耐受或依赖的中度至重度活动期 UC 和 CD 患者。在中度至重度 CD 和 UC 患者中按照批准的剂量给药时，维得利珠单抗在第 6 周诱导临床缓解率分别高达 31.4%和 47.1%，在第 52 周诱导临床缓解率分别高达 39%和 41.8%。维得利珠单抗报告的严重不良事件包括严重感染、恶性肿瘤和过敏反应。由于维得利珠单抗具有胃肠道选择性，迄今为止，它没有显示出引起进行性多灶性白质脑病的证据；然而，正在进行上市后监测该不良反应的研究。进一步评估维得利珠单抗在这些疾病早期的应用以及与其他疗法联合应用的价值是必要的。
