Normalization of mucosal tumor necrosis factor-α: A new criterion for discontinuing infliximab therapy in ulcerative colitis
Normalization of mucosal tumor necrosis factor-α: A new criterion for discontinuing infliximab therapy in ulcerative colitis
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DOI：
10.1016/j.cyto.2015.12.021
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发表时间：
2016-03-01
期刊：
影响因子：
3.8
通讯作者：
Florholmen, Jon
中科院分区：
文献类型：
--
作者：
Olsen, Trine;Rismo, Renathe;Florholmen, Jon
背景：抗肿瘤坏死因子（TNF）等生物制剂可诱导溃疡性结肠炎的缓解。然而，对于停止这种治疗尚未达成共识。目的：本研究的目的是评估临床参数和愈合结肠粘膜中的粘膜细胞因子 mRNA 是否可以预测英夫利昔单抗 (IFX) 治疗停止后溃疡性结肠炎的长期缓解。方法：前瞻性特罗姆瑟炎症性肠病 (IBD) 研究基于 IFX 强化诱导治疗算法，以实现疾病缓解。临床和内镜缓解后，停止 IFX 治疗，并随访直至复发。纳入 IFX 诱导疗程后获得临床和内镜缓解的患者。通过结肠镜检查获得的粘膜活检中的实时 PCR 定量 TNF α (TNF)、干扰素 γ (IFNG)、白细胞介素 (IL) 6 (IL6)、IL17A、IL23 和转化生长因子 β (TGFB) 的表达水平。缓解定义为溃疡性结肠炎疾病活动指数 (UCDAI) 低于 3，内窥镜评分为 0-1。复发定义为 UCDAI 评分 >3 且内镜分项评分 >1。 20 名结肠镜检查正常的非 IBD 患者的粘膜细胞因子转录水平作为对照组。 结果：在 45 名患者中，20 名患者 (44%) 在粘膜愈合时粘膜 TNF 表达水平正常化，而 42 名患者中的 35 名 (83%) 具有正常化的 IL17A 表达水平，36 名患者中的 31 名 (86%) 具有正常化的 IFNG 表达水平。复发的中位时间为 8 个月（范围 4-12）。 TNF 基因表达正常化预测 IFX 停药后 20 个月（1-39）无复发生存期，而 TNF 表达升高组则为 5 个月（3-7）个月。 IL17A、IL23、IFNG、TGFB、IL6 粘膜表达水平不能预测长期缓解（>12 个月）结论：粘膜 TNF 正常化可预测停用 IFX 后的长期缓解。 (C) 2016 年由爱思唯尔有限公司出版。
Background: Biological agents such as antitumor necrosis factor (TNF) induce remission in ulcerative colitis. There is however no consensus regarding the discontinuation of this treatment. Aim: The aim of this study is to assess whether clinical parameters and mucosal cytokine mRNAs in healed colonic mucosa can predict long-term remission in ulcerative colitis following discontinuation of infliximab (IFX) therapy.Methods: The prospective Tromso Inflammatory Bowel Disease (IBD) Study is based on an intensified induction treatment algorithm with IFX to achieve disease remission. Following clinical and endoscopic remission, IFX treatment was discontinued, and follow-up until relapse was performed. Patients who achieved clinical and endoscopic remission following an induction course of IFX were included. Expression levels of TNF alpha (TNF), interferon gamma (IFNG), interleukin (IL) 6 (IL6), IL17A, IL23, and transforming growth factor beta (TGFB) were quantified by real-time PCR in mucosal biopsies obtained at colonoscopy. Remission was defined as Ulcerative Colitis Disease Activity Index (UCDAI) below 3, and an endoscopic subscore of 0-1. Relapse was defined as UCDAI score >3 and endoscopic subscore >1. Mucosal cytokine transcript levels from 20 non-IBD patients with a normal colonoscopy served as control group.Results: Of the 45 patients included, twenty patients (44%) had normalized levels of mucosal TNF expression at the time of mucosal healing, whereas 35 of 42 (83%) had normalized IL17A expression levels, and 31 of 36 (86%) had normalized IFNG expression levels. The median time to relapse was 8 months (range 4-12). Normalization of TNF gene expression predicted 20 months (1-39) relapsefree survival after withdrawal of IFX compared to 5 months (3-7) in the group with elevated TNF expression. Mucosal expression levels of IL17A, IL23, IFNG, TGFB, IL6 did not predict long-term remission (>12 months)Conclusion: Normalization of mucosal TNF predicts long-term remission after discontinuation of IFX. (C) 2016 Published by Elsevier Ltd.