Inflammatory Cytokine Profile in Crohn's Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy.
Inflammatory Cytokine Profile in Crohn's Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy.
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克罗恩病对最佳抗肿瘤坏死因子治疗无反应者的炎症细胞因子谱。
DOI：
10.1097/mcg.0000000000001002
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发表时间：
2019-03
影响因子：
2.9
通讯作者：
Abreu MT
中科院分区：
文献类型：
--
作者：
Yarur AJ;Jain A;Quintero MA;Czul F;Deshpande AR;Kerman DH;Abreu MT
大量接受抗肿瘤坏死因子（TNF）药物治疗克罗恩病（CD）的患者出现原发性或继发性无应答。本研究的目的是评估对抗TNF药物无应答的患者是否增加了替代细胞因子途径的表达。我们设计了一项前瞻性、横断面研究，纳入接受抗TNF治疗的CD患者，这些患者接受结肠镜检查，血清药物谷浓度足够（≥8 μg/mL）且无抗药抗体。测量的炎性细胞因子和细胞粘附标志物包括细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）、白细胞介素-（IL）8、IL-1β和IL-6。主要结局是存在活动性内镜炎症，定义为至少存在一处溃疡≥5 mm。纳入47例患者。与没有肠道炎症的患者相比，活动性炎症患者的ICAM-1和IL-1β水平显著更高（分别为45.9 vs. 35.8 ng/mL，p<0.0001和3.2 vs. 1.5 pg/mL，p=0.002）。其他研究变量无显著差异。使用接收工作曲线，ICAM和IL-1β与“抗TNF抵抗”患者队列中的炎症具有良好的相关性（ROC≥0.8）。既往抗TNF暴露患者组的结果相似。我们的研究表明，具有活动性炎症且血清抗TNF水平似乎足够的患者具有增加的特定炎症途径水平，其可作为无应答的生物标志物以及抗TNF无应答者的潜在治疗靶点。
A significant number of patients receiving therapy with anti-tumor necrosis factor (TNF) agents for Crohn’s disease (CD) experience primary or secondary non-response. The aim of this study was to assess if patients with non-response to anti-TNF agents have increased expression of alternative cytokine pathways. We designed a prospective, cross-sectional study that included patients with CD receiving anti-TNF undergoing colonoscopy with adequate serum trough drug levels (≥8 μg/mL) and without anti-drug antibodies. Inflammatory cytokines and cell adhesions markers measured included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin-(IL) 8, IL-1β and IL-6. The primary outcome was the presence of active endoscopic inflammation defined as the presence of at least one ulceration ≥5 mm. 47 patients were included. Patients with active inflammation had significantly higher levels of ICAM-1 and IL-1β when compared to those without intestinal inflammation (45.9 vs. 35.8 ng/mL, p<0.0001 and 3.2 vs. 1.5 pg/mL, p=0.002 respectively). There were no significant differences in the other study variables. Using receiving operating curves, ICAM and IL-1β had a good correlation (ROC≥0.8) with inflammation in this cohort of patients with “anti-TNF resistance.” The results were similar in the group of patients with previous anti-TNF exposure. Our study suggests that patients who have active inflammation with seemingly adequate serum anti-TNF levels have increased levels of specific inflammatory pathways that may serve as biomarkers of non-response as well as potential targets of therapy in anti-TNF non-responders.