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溃疡性结肠炎中抗肿瘤坏死因子治疗反应的预测因素

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

作者信息

Zampeli Evanthia, Gizis Michalis, Siakavellas Spyros I, Bamias Giorgos

机构信息

Evanthia Zampeli, Gastroenterology Department, Alexandra General Hospital, 11528 Athens, Greece.

出版信息

World J Gastrointest Pathophysiol. 2014 Aug 15;5(3):293-303. doi: 10.4291/wjgp.v5.i3.293.

Abstract

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

摘要

溃疡性结肠炎(UC)是一种免疫介导的大肠慢性炎症性疾病。其病程的特点是急性炎症发作以及低度慢性炎症活动期或缓解期。抗肿瘤坏死因子单克隆抗体(抗TNF)是治疗药物的一部分,用于治疗对皮质类固醇和/或免疫抑制剂常规治疗无效的中度至重度UC患者。对这些药物的治疗反应并不一致,很大一部分患者要么没有改善(原发性无反应),要么在一段时间的改善后失去反应(继发性无反应/反应丧失)。此外,抗TNF药物的使用与罕见但可能严重的不良反应有关,这些不良反应会妨碍药物的使用或导致停药。最后,使用这些药物会给卫生系统带来相当大的成本。识别可能预测UC患者对抗TNF药物反应的参数,将有助于更好地选择有高反应概率的患者,并将无反应患者的风险和成本降至最低。对主要临床试验以及在UC中使用抗TNF药物的累积经验进行分析后,得出了此类预后因素的报告。其中包括临床和流行病学特征、实验室指标、内镜指标以及分子(免疫/遗传)特征。这些长期预后的预测参数可能在治疗开始时就已存在,或者在治疗早期确定。在具有不同特征的大量患者队列中验证这些预后标志物,将有助于将它们引入临床实践,并更好地选择将从抗TNF治疗中获益的UC患者。

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