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Antiarrhythmic Potential of Anticytokine Therapy in Rheumatoid Arthritis: Tocilizumab Reduces Corrected QT Interval by Controlling Systemic Inflammation

机译:类风湿性关节炎抗型视线治疗的抗炎潜力:通过控制系统性炎症来减少矫正QT间隔

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Objective. Patients with rheumatoid arthritis (RA) are twice as likely to experience sudden cardiac death compared with individuals without RA. Although the underlying mechanisms of this have not been clarified, evidence points to the effects of systemic inflammation on ventricular repolarization. Accordingly, prolongation of the corrected QT (QTc) interval is more frequent in patients with RA compared with individuals without RA also correlating with C-reactive protein (CRP) and predicting all-cause mortality. Tocilizumab (TCZ) is an anti-interleukin-6 receptor antibody that potently inhibits inflammatory activation in RA, with rapid normalization of acute-phase reactant levels, including the CRP level. Therefore, we hypothesized that TCZ may normalize the QTc interval by dampening systemic inflammation, thus reducing the risk of arrhythmia in patients with RA.Methods. Seventeen consecutive patients with active RA who were scheduled to receive TCZ once every 4 weeks underwent a clinical examination, electrocardiography, and blood sampling just before the first injection with TCZ and again after 3 months and 6 months of treatment.Results. At baseline, 76% of patients displayed prolongation of the QTc interval (mean ?SD 452.3 ?35.8 msec). TCZ treatment was associated with a rapid and significant reduction of the QTc interval to mean values <440 msec (up to 428.1 ?34.3 msec). Throughout the study, QTc interval shortening correlated with decreases in both the CRP level, and more strongly, with circulating tumor necrosis factor a level.Conclusion. These data provide further evidence of the close link between the degree of systemic inflammation and QTc interval duration in RA and also suggest an anti-arrhythmic potential for TCZ treatment, which may have a beneficial impact on the mortality of these patients.
机译:客观的。类风湿性关节炎(RA)的患者与没有RA的个体相比,与个体相比,突然的心脏死亡的可能性是突然的心脏死亡。虽然没有澄清这一点的潜在机制,但证据指出了全身炎症对心室复极性的影响。因此,与RA的患者相比,校正的QT(QTC)间隔的延长更频繁地与没有RA的个体也与C反应蛋白(CRP)相关并预测全导致死亡率。 Tocilizumab(TCZ)是一种抗白细胞介素-6受体抗体,其效果抑制RA中的炎症活化,快速归一化急性相反应物水平,包括CRP水平。因此,我们假设TCZ可以通过阻尼的系统性炎症来使QTC间隔正常化,从而降低RA.Methods患者心律失常的风险。 17名连续患有活跃RA的患者每4周预定接受TCZ的临床检查,心电图和血液取样,恰好在第一次注射TCZ之前,在3个月和6个月的治疗后再次进行。结果。在基线,76%的患者显示QTC间隔的延长(平均值?SD 452.3?35.8毫秒)。 TCZ治疗与QTC间隔的快速显着减少到平均值<440毫秒(最高428.1毫秒)。在整个研究中,QTC间隔缩短与CRP水平的降低相关,更强烈,循环肿瘤坏死因子A水平。结论。这些数据提供了进一步证明了RA的全身炎症程度和QTC间隔持续时间之间的密切联系,并且还表明TCZ治疗的抗心律失常潜力,这可能对这些患者的死亡率有益影响。

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