Tocilizumab Increases Serum Lipids but Does Not Increase Arteriosclerosis, As Measured by Intima-Media Thickness, in Patients With Rheumatoid Arthritis.

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.
Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Medical Research Ethics Committee, Shimane University Faculty of Medicine issued approval (416). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: MT, MH, and YS have nothing to declare. MM has received honoraria for lectures from Ayumi Pharma Corporation, Eisai Co. Ltd, Eli Lilly Japan K.K., Taisyo Pharma Corporation, and Mitsubishi Tanabe Pharma Corporation. YM has received honoraria from for lectures AbbVie Japan GK, Asahi Kasei Pharma Co. Ltd., Astellas Pharma Inc., AstraZeneca, AYUMI Pharma Corp., Bristol Myers Squibb Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Mitsubishi-Tanabe Co Ltd., MSD, Ono Pharmaceutical Co Ltd. and UCB Japan Co. Ltd. MK has received grants from Janssen Pharma K.K., GlaxoSmithKline, K.K., Pfizer Inc., Zenyaku Kogyo Co. Ltd., and Cmic Co. Ltd., and has received speaking fee from Eisai Co. Ltd., Chugai Pharma Co. Ltd., Mitsubishi-Tanabe Pharma, Bristol-Myers Squibb, Janssen Pharma K.K., Astellas Pharma Inc., Takeda Pharma Co. Nippon Kayaku Co. Ltd, Daiichi-Sankyo Co. Ltd, Asahi Kasei Pharma Co. and AbbVie Japan. KI has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the following companies: AstraZeneca K.K., Asahi Kasei Pharma Corporation, GlaxoSmithKline K.K., Eli Lilly Japan K.K., AbbVie G.K., Taisho Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
(Copyright © 2025, Moriyama et al.)