Effects of Tocilizumab, an Anti-Interleukin-6 Receptor Antibody, on Serum Lipid and Adipokine Levels in Patients with Rheumatoid Arthritis.

Elinoar Hoffman,Joy Feld,Tal Gazitt,Devy Zisman,Idit Lavie,Michal A Rahat,Muna Elias,Itzhak Rosner,Lisa Kaly

doi:10.3390/ijms20184633

Abstract

Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. Dyslipidemia is a known adverse effect of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody used in RA treatment. We aimed to assess the effect of TCZ on lipid profile and adipokine levels in RA patients. Height, weight, disease activity scores, lipid profile and atherogenic indices (AI), leptin, adiponectin, resistin, interleukin-6, and high-sensitivity C-reactive protein (CRP) were measured before and four months after initiation of TCZ in 40 RA patients and 40 healthy controls. Following TCZ treatment, total cholesterol, high density lipoprotein (HDL), and triglycerides were significantly elevated, but no significant changes in weight, body mass index (BMI), low density lipoprotein (LDL), and AI were observed. Compared with controls, significantly higher adiponectin levels were measured in the RA group at baseline. Following TCZ treatment, resistin levels and the leptin-to-adiponectin ratio increased, adiponectin levels decreased, and leptin levels remained unchanged. No correlation was found between the change in adipokine serum levels and changes in the disease activity indices, nor the lipid profile. In conclusion, the changes observed suggest a protective role for TCZ on the metabolic and cardiovascular burden associated with RA, but does not provide a mechanistic explanation for this phenomenon.

Highlights

Rheumatoid arthritis (RA), a chronic inflammatory disease with typical bone erosion and damage, is associated with an increased incidence of metabolic syndrome and cardiovascular disease (CVD)
We show that TCZ treatment improves disease activity and reduces the inflammatory burden in RA patients, as has been shown before
Disease activity scores were significantly reduced with TCZ treatment, as were the values of high sensitivity CRP (hsCRP), a measure considered to reflect vascular inflammation and that serves as a predictor of cardiovascular events [1]

Summary

Introduction

Rheumatoid arthritis (RA), a chronic inflammatory disease with typical bone erosion and damage, is associated with an increased incidence of metabolic syndrome and cardiovascular disease (CVD). It is suggested that successful treatment of RA patients so as to reduce the inflammatory burden may decrease CVD risk [2,3,4] This has already been shown for the administration of tumor necrosis factor-alpha (TNF-α) inhibitors [5]. Adipokines, cytokines secreted mostly by white adipose tissue, are involved in inflammation, endothelial dysfunction, and atherosclerosis, placing them as possible molecular links between RA, the metabolic syndrome, and CVD risk [2,6,7,8]. Their putative role as key inflammatory mediators contributing to CVD risk is still controversial, as their serum levels vary. The leptin-to-adiponectin ratio (LAR) is used to assess insulin resistance among type-2 diabetes mellitus patients and healthy individuals [14,15,16,17,18], while resistin levels were found to correlate with insulin resistance in septic patients [6]

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