Moriyama Mayuko, Murakawa Yohko, Kondo Masahiro, Taira Mariko, Sumita Yoshiko, Honda Manabu, Ichinose Kunihiro
Department of Rheumatology, Shimane University Faculty of Medicine, Izumo, JPN.
Department of Internal Medicine III, Shimane University Faculty of Medicine, Izumo, JPN.
Cureus. 2025 Jan 2;17(1):e76782. doi: 10.7759/cureus.76782. eCollection 2025 Jan.
Objectives Patients with rheumatoid arthritis (RA) have a high incidence of arteriosclerotic disease. These are partly attributed to high levels of C-reactive protein (CRP) and inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. Tocilizumab (TCZ) is an IL-6 receptor antagonist that lowers CRP levels by directly blocking IL-6 signaling. Tocilizumab has been reported to increase serum lipid levels. However, its effect on arteriosclerosis remains unclear. Therefore, we investigated the effect of TCZ on arteriosclerosis in patients with RA. Methods Eighteen Japanese patients with RA who were administered TCZ were included and assessed at baseline and six and 12 months. The Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR), CRP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and carotid intima-media thickness (IMT) were measured and analyzed using high-resolution B-mode ultrasonography. Additionally, the effects of concurrent statin administration on any changes in IMT were evaluated. Results From baseline to six or 12 months, TCZ decreased CRP (P < 0.0005) and DAS28-ESR (P < 0.0005) significantly, whereas TC, LDL-C, and HDL-C levels increased significantly (P < 0.005). However, there was no change in the LDL-C/HDL-C ratio (P = 0.821 at six months and P = 0.168 at 12 months), and carotid IMT (P = 0.6874 at six months and P = 0.6951 at 12 months). Comparison of percentage changes in mean IMT revealed no statistical differences between the patient groups with or without statin administration (P = 0.7208 at six months, P = 0.5928 at 12 months). Conclusions According to the 12-month observation data, no significant association was detected between TCZ use and IMT changes in patients with RA, despite its effects on serum lipids. Further long-term studies are needed to confirm that IL-6 receptor blockers have cardiovascular effects.
目的 类风湿关节炎（RA）患者的动脉粥样硬化疾病发病率较高。这部分归因于高水平的C反应蛋白（CRP）以及炎性细胞因子，如肿瘤坏死因子-α（TNF-α）和白细胞介素（IL）-6。托珠单抗（TCZ）是一种IL-6受体拮抗剂，可通过直接阻断IL-6信号传导来降低CRP水平。据报道，托珠单抗会升高血脂水平。然而，其对动脉粥样硬化的影响仍不清楚。因此我们研究了托珠单抗对RA患者动脉粥样硬化的影响。方法 纳入18例接受托珠单抗治疗的日本RA患者，在基线、6个月和12个月时进行评估。采用高分辨率B型超声测量并分析疾病活动评分28（DAS28）联合红细胞沉降率（ESR）、CRP、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）以及颈动脉内膜中层厚度（IMT）。此外，评估了同时服用他汀类药物对IMT变化的影响。结果 从基线到6个月或至12个月时，托珠单抗使CRP（P<0.0005）和DAS28-ESR（P<0.0005）显著降低，而TC、LDL-C和HDL-C水平显著升高（P<0.005）。然而，LDL-C/HDL-C比值没有变化（6个月时P=0.821，12个月时P=0.168），颈动脉IMT也没有变化（6个月时P=0.68(74)，12个月时P=0.6951）。比较平均IMT的百分比变化发现，服用或未服用他汀类药物的患者组之间无统计学差异（6个月时P=0.7208，12个月时P=0.5928）。结论 根据12个月的观察数据，尽管托珠单抗对血脂有影响，但在RA患者中未检测到托珠单抗使用与IMT变化之间存在显著关联。需要进一步的长期研究来证实IL-6受体阻滞剂具有心血管效应。
