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抗肿瘤坏死因子-α 治疗与银屑病关节炎和类风湿关节炎患者的血流介导的血管舒张变化。

Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients.

机构信息

Department of Internal Medicine, Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza, Opera di Padre Pio da Pietrelcina, Cappuccini Avenue, 71013 S. Giovanni Rotondo (FG), Italy.

出版信息

Intern Emerg Med. 2010 Dec;5(6):495-500. doi: 10.1007/s11739-010-0458-6. Epub 2010 Sep 16.

Abstract

For a long time, the endothelial covering of the vessels has been considered an inert surface. On the contrary, the endothelial cells are active and dynamic elements in the interaction between blood and tissues. The control of the vessel basal tone is obtained by the complex balance between the relaxing and contracting endothelial factors. Previous clinical studies show that patients suffering from rheumatoid arthritis and other autoimmune rheumatologic pathologies are at high risk of death being prematurely affected by atherosclerosis and cardiovascular diseases. Blocking tumor necrosis factor (TNF)-α by biological drugs improves the endothelial function. The aim of our study was to evaluate the effects of two anti-TNF-α drugs (infliximab and etanercept) on the endothelial function by evaluating the flow-mediated dilatation (FMD), which was measured in the brachial artery before and after treatment and after 8-12 weeks. We enrolled 36 patients (average age 52 ± 9.8 years, 12 men and 24 women), 25 of them were affected by rheumatoid arthritis (RA) and 11 were affected by psoriatic arthritis (PsA) and they were divided into three groups: 10 patients were treated with etanercept, 13 patients were treated with infliximab, 13 patients were treated with DMARDs. We measured the common carotid intimal-medial thickness (ccIMT) and the endothelial function was evaluated by FMD measurement in the brachial artery, before treatment, 1 h after the beginning of treatment and after 8-12 weeks. No statistically significant difference between the three groups was found for the ultrasonographic evaluation of the carotid IMT. On the contrary, the differences between FMD values before and after the treatment in the patients treated with etanercept (13.1 ± 0.01 vs. 18.8 ± 0.01%, p < 0.01) and in the patients treated with infliximab (11.8 ± 0.09 vs. 16.7 ± 0.09%, p < 0.01) were statistically significant. Long-term evaluation for infliximab and etanercept was performed by comparing the FMD values, respectively, 8 and 12 weeks after the first treatment. After 8 weeks, FMD value was similar to the value recorded at enrollment in the infliximab group (11.9 ± 0.03 vs. 13.54 ± 0.04%, p = 0.236) and the FMD values in the etanercept group after 12 weeks showed a not statistically significant reduction of vasodilatating effect (13.01 ± 0.03 vs. 15.67 ± 0.02%, p = 0.197). In conclusion, the use of biological drugs in patients affected by autoimmune arthritis can modify the endothelial function, as indicated by the induced FMD changes, but the long-term effect tends to be considerably reduced.

摘要

长期以来,血管内皮细胞一直被认为是一种惰性表面。相反,内皮细胞是血液与组织相互作用中活跃而动态的元素。血管基础张力的控制是通过舒张和收缩内皮因子之间的复杂平衡来实现的。先前的临床研究表明,患有类风湿关节炎和其他自身免疫性风湿病的患者因动脉粥样硬化和心血管疾病而提前死亡的风险很高。通过生物药物阻断肿瘤坏死因子 (TNF)-α 可改善内皮功能。我们的研究目的是通过评估肱动脉血流介导的舒张 (FMD) 来评估两种抗 TNF-α 药物(英夫利昔单抗和依那西普)对内皮功能的影响,该舒张在治疗前、治疗后 1 小时和 8-12 周后进行测量。我们招募了 36 名患者(平均年龄 52 ± 9.8 岁,12 名男性和 24 名女性),其中 25 名患有类风湿关节炎 (RA),11 名患有银屑病关节炎 (PsA),他们分为三组:10 名患者接受依那西普治疗,13 名患者接受英夫利昔单抗治疗,13 名患者接受 DMARDs 治疗。我们测量了颈总动脉内膜中层厚度 (ccIMT),并通过肱动脉 FMD 测量评估内皮功能,在治疗前、治疗开始后 1 小时和 8-12 周后进行测量。在颈动脉 IMT 的超声评估方面,三组之间未发现统计学差异。相反,接受依那西普治疗的患者 (13.1 ± 0.01 对 18.8 ± 0.01%,p < 0.01) 和接受英夫利昔单抗治疗的患者 (11.8 ± 0.09 对 16.7 ± 0.09%,p < 0.01) 的 FMD 值在治疗前后的差异具有统计学意义。通过比较首次治疗后 8 周和 12 周的 FMD 值,对英夫利昔单抗和依那西普进行了长期评估。8 周后,英夫利昔单抗组的 FMD 值与入组时记录的值相似(11.9 ± 0.03 对 13.54 ± 0.04%,p = 0.236),而依那西普组 12 周后的 FMD 值显示血管舒张作用无统计学意义降低(13.01 ± 0.03 对 15.67 ± 0.02%,p = 0.197)。总之,在自身免疫性关节炎患者中使用生物药物可以改变内皮功能,这可以通过诱导的 FMD 变化来指示,但长期效果往往会大大降低。

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