类风湿关节炎的心率校正 QT 间期持续时间及其用白细胞介素 6 抑制剂托珠单抗治疗的降低。
Heart Rate-corrected QT Interval Duration in Rheumatoid Arthritis and Its Reduction with Treatment with the Interleukin 6 Inhibitor Tocilizumab.
机构信息
From the Division of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo; Department of Advanced Biomedical Imaging Informatics, St. Marianna University School of Medicine, Kawasaki, Japan; Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
H. Kobayashi, MD, PhD, Division of Hematology and Rheumatology, Nihon University School of Medicine; Y. Kobayashi, MD, PhD, Department of Advanced Biomedical Imaging Informatics, St. Marianna University School of Medicine; I. Yokoe, MD, Division of Hematology and Rheumatology, Nihon University School of Medicine; N. Kitamura, MD, Division of Hematology and Rheumatology, Nihon University School of Medicine; A. Nishiwaki, MD, Division of Hematology and Rheumatology, Nihon University School of Medicine; M. Takei, MD, PhD, Division of Hematology and Rheumatology, Nihon University School of Medicine; J.T. Giles, MD, MPH, Division of Rheumatology, Columbia University, College of Physicians and Surgeons.
出版信息
J Rheumatol. 2018 Dec;45(12):1620-1627. doi: 10.3899/jrheum.180065. Epub 2018 Sep 1.
OBJECTIVE
Individuals with rheumatoid arthritis (RA) are at a heightened risk of sudden cardiac death, an outcome increased in those with prolongation of the corrected electrocardiographic QT interval (QTc). We compared QTc between patients with RA and demographically matched controls and studied the change in QTc after treatment with the interleukin 6 inhibitor tocilizumab (TCZ).
METHODS
Standard 12-lead electrocardiograms were obtained and QTc was measured in patients with RA at baseline and after 24 weeks of TCZ treatment, then compared with non-RA controls who were frequency-matched on age and sex. Indicators of the baseline QTc and predictors of change in QTc were studied using multivariable linear regression.
RESULTS
A total of 94 RA and 42 non-RA controls were studied. The average baseline QTc was 10 ms longer in the RA group vs controls (422 vs 412 ms, respectively; p < 0.001) and decreased to an average of 406 ms with treatment (p < 0.001). Baseline QTc was significantly and independently higher among those with anticyclic citrullinated peptide antibodies seropositivity, higher swollen joint counts, and higher levels of C-reactive protein (CRP) and matrix metalloproteinase 3. Each log unit decrease in CRP with treatment was associated with an average reduction in QTc of 2.9 ms (p = 0.002) after adjusting for age and baseline QTc. Clinical response measures were not associated with the change in QTc.
CONCLUSION
The marked normalization of QTc observed with TCZ treatment, and its close parallel with CRP reduction, support the premise that systemic inflammation contributes to cardiac repolarization abnormalities in RA that may be amenable to treatment.
目的
患有类风湿关节炎（RA）的个体发生心脏性猝死的风险较高，而心电图 QT 间期校正（QTc）延长的患者风险更高。我们比较了 RA 患者与人口统计学匹配的对照组之间的 QTc，并研究了白细胞介素 6 抑制剂托珠单抗（TCZ）治疗后 QTc 的变化。
方法
在 RA 患者接受 TCZ 治疗 24 周前后，获得标准 12 导联心电图并测量 QTc，然后与年龄和性别频率匹配的非 RA 对照组进行比较。使用多变量线性回归研究基线 QTc 的指标和 QTc 变化的预测因素。
结果
共纳入 94 例 RA 和 42 例非 RA 对照组。RA 组的平均基线 QTc 比对照组长 10 毫秒（分别为 422 毫秒和 412 毫秒，p < 0.001），治疗后平均降至 406 毫秒（p < 0.001）。抗环瓜氨酸肽抗体阳性、关节肿胀计数较高和 C 反应蛋白（CRP）和基质金属蛋白酶 3 水平较高的患者，基线 QTc 显著且独立升高。治疗后 CRP 每降低 1 个对数单位，平均 QTc 降低 2.9 毫秒（p = 0.002），调整年龄和基线 QTc 后。临床反应措施与 QTc 的变化无关。
结论
TCZ 治疗后观察到 QTc 明显正常化，且与 CRP 降低密切平行，支持系统性炎症导致 RA 心脏复极异常的前提，这可能是可治疗的。
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