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托法替布用于治疗对抗肿瘤坏死因子和抗整合素疗法难治的溃疡性结肠炎

TOFACITINIB IN THE MANAGEMENT OF ULCERATIVE COLITIS REFRACTORY TO ANTI-TNF AND ANTI-INTEGRIN THERAPIES.

作者信息

Teixeira Fábio Vieira, Damião Adérson Omar Mourão Cintra, Kotze Paulo Gustavo

机构信息

Clínica GastroSaúde, Marília, SP, Brasil.

Universidade de São Paulo, Faculdade de Medicina, Departamento de Gastroenterologia, São Paulo, SP, Brasil.

出版信息

Arq Gastroenterol. 2018 Apr-Jun;55(2):198-200. doi: 10.1590/S0004-2803.201800000-36.

Abstract

Janus kinases inhibitors have already been incorporated into the management of immune-mediated diseases, such as rheumatoid arthritis, and are being investigated for the treatment of psoriasis and inflammatory bowel diseases, both ulcerative colitis and Crohn's disease. Tofacitinib is an oral small-molecule drug that inhibits Janus kinases 1, Janus kinases 3, and, to a lesser extent, Janus kinases 2. This inhibition ends up blocking signals for several inflammatory cytokines that are involved in the pathogenesis of inflammatory bowel diseases and play a role in many immune signaling routes, including lymphocyte activation, function, and proliferation. We report a patient with active ulcerative colitis with primary non-response to three biologics (infliximab, adalimumab and vedolizumab), with different mechanisms of action, who refused surgical treatment and had a favorable response to tofacitinib with clinical and endoscopic remission. No adverse events were observed with the use of the agent. This case illustrates the difficulties we may face regarding the identification of the expression of proper mechanism of action involved in the pathogenesis of ulcerative colitis patients and the importance of having another treatment option with different mechanism of action, like tofacitinib.

摘要

Janus激酶抑制剂已被纳入免疫介导疾病(如类风湿性关节炎)的治疗方案中,并且正在研究其用于治疗银屑病以及炎症性肠病(包括溃疡性结肠炎和克罗恩病)。托法替布是一种口服小分子药物,可抑制Janus激酶1、Janus激酶3,在较小程度上还可抑制Janus激酶2。这种抑制作用最终会阻断多种炎性细胞因子的信号,这些细胞因子参与炎症性肠病的发病机制,并在许多免疫信号通路中发挥作用,包括淋巴细胞的激活、功能和增殖。我们报告了一名患有活动性溃疡性结肠炎的患者,该患者对三种作用机制不同的生物制剂(英夫利昔单抗、阿达木单抗和维多珠单抗)原发性无反应,拒绝手术治疗,而对托法替布有良好反应,实现了临床和内镜缓解。使用该药物未观察到不良事件。该病例说明了我们在确定溃疡性结肠炎患者发病机制中适当作用机制的表达方面可能面临的困难,以及拥有另一种作用机制不同的治疗选择(如托法替布)的重要性。

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