Bacchiega Bruno Cesar, Bacchiega Ana Beatriz, Usnayo Magali Justina Gomez, Bedirian Ricardo, Singh Gurkirpal, Pinheiro Geraldo da Rocha Castelar
Department of Internal Medicine, Rio de Janeiro State University, Rio de Janeiro, Brazil
Discipline of Rheumatology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
J Am Heart Assoc. 2017 Mar 13;6(3):e005038. doi: 10.1161/JAHA.116.005038.
Atherosclerosis is a chronic inflammatory disease, with interleukin 6 (IL-6) as a major player in inflammation cascade. IL-6 blockade may reduce cardiovascular risk, but current treatments to block IL-6 also induce dyslipidemia, a finding with an uncertain prognosis.
We aimed to determine the endothelial function responses to the IL-6-blocking agent tocilizumab, anti-tumor necrosis factor α, and synthetic disease-modifying antirheumatic drug therapies in patients with rheumatoid arthritis in a 16-week prospective study. Sixty consecutive patients with rheumatoid arthritis were enrolled. Tocilizumab and anti-tumor necrosis factor α therapy were started in 18 patients each while 24 patients were treated with synthetic disease-modifying antirheumatic drugs. Forty patients completed the 16-week follow-up period. The main outcome was flow-mediated dilation percentage variation before and after therapy. In the tocilizumab group, flow-mediated dilation percentage variation increased statistically significantly from a pre-treatment mean of (3.43% [95% CI, 1.28-5.58] to 5.96% [95% CI, 3.95-7.97]; =0.03). Corresponding changes were 4.78% (95% CI, 2.13-7.42) to 6.75% (95% CI, 4.10-9.39) (=0.09) and 2.87% (95% CI, -2.17 to 7.91) to 4.84% (95% CI, 2.61-7.07) (=0.21) in the anti-tumor necrosis factor α and the synthetic disease-modifying antirheumatic drug groups, respectively (both not statistically significant). Total cholesterol increased significantly in the tocilizumab group from 197.5 (95% CI, 177.59-217.36) to 232.3 (201.62-263.09) (=0.003) and in the synthetic disease-modifying antirheumatic drug group from 185.8 (95% CI, 169.76-201.81) to 202.8 (95% CI, 176.81-228.76) (=0.04), but not in the anti-tumor necrosis factor α group. High-density lipoprotein did not change significantly in any group.
Endothelial function is improved by tocilizumab in a high-risk population, even as it increases total cholesterol and low-density lipoprotein levels.
动脉粥样硬化是一种慢性炎症性疾病，白细胞介素6（IL-6）是炎症级联反应中的主要参与者。阻断IL-6可能会降低心血管风险，但目前阻断IL-6的治疗方法也会诱发血脂异常，这一发现的预后尚不确定。
在一项为期16周的前瞻性研究中，我们旨在确定类风湿性关节炎患者对IL-6阻断剂托珠单抗、抗肿瘤坏死因子α以及合成抗风湿药物治疗的内皮功能反应。连续纳入60例类风湿性关节炎患者。18例患者开始使用托珠单抗治疗，18例患者开始使用抗肿瘤坏死因子α治疗，24例患者使用合成抗风湿药物治疗。40例患者完成了16周的随访期。主要结局是治疗前后血流介导的血管舒张百分比变化。在托珠单抗组，血流介导的血管舒张百分比变化从治疗前的平均（3.43%[95%CI，1.28 - 5.58]）显著增加至5.96%（95%CI，3.95 - 7.97）；P = 0.03。在抗肿瘤坏死因子α组和合成抗风湿药物组中，相应变化分别为4.78%（95%CI，2.13 - 7.42）至6.75%（95%CI，4.10 - 9.39）（P = 0.09）和2.87%（95%CI， - 2.17至7.91）至4.84%（95%CI，2.61 - 7.07）（P = 0.21）（两者均无统计学意义）。托珠单抗组总胆固醇从197.5（95%CI，177.59 - 217.36）显著增加至232.3（201.62 - 263.09）（P = 0.003），合成抗风湿药物组从185.8（95%CI，169.76 - 201.81）增加至202.8（95%CI，176.81 - 228.76）（P = 0.04），但抗肿瘤坏死因子α组未出现这种情况。任何一组的高密度脂蛋白均无显著变化。
在高危人群中，托珠单抗可改善内皮功能，即便它会增加总胆固醇和低密度脂蛋白水平。
