Tocilizumab Effect on Lipid Profile in Correlation to Cardiovascular Events: A Retrospective Cohort Study

Abstract

Objective. To study the effect of tocilizumab initiation on the lipid profile, in correlation to a composite of any cardiovascular events. Methods. A retrospective cohort study, using data from the King Faisal Specialist Hospital & Research Centre database, from January 2014 to December 2019. Patients with rheumatoid arthritis or juvenile idiopathic arthritis who were ≥18 years old, initiated either on tocilizumab or other biologic treatment (anti-TNFs or Rituximab), were included, with a follow-up interval duration at a minimum of 6–12 months up to 3-5 years. Any patient with established cardiovascular disease or aged <18 were excluded. Results. Only one cardiovascular mortality was reported in the tocilizumab group. Fifty percent of patients reached high cholesterol levels ≥ 5.2 mmol / L and LDL ≥ 3.37 mmol / L in the tocilizumab group at 36 months in a shorter time period compared to controls (60 months), P 0.001. There were no significant differences between groups for statin use (27% vs. 28%) However, there was a significantly higher mean dose of atorvastatin in the tocilizumab group compared to controls (20.6 mg vs. 16.6 mg, P 0.03). Conclusion. There was a lack of evidence of increased cardiovascular risk in correlation to hyperlipidemia secondary to tocilizumab treatment.

Tocilizumab improves clinical outcome in patients with active corticosteroid-resistant moderate-to-severe Graves’ orbitopathy: an observational study

“…Total cholesterol, highdensity lipoprotein (HDL) and triglycerides seem to be significantly elevated with little or no effect in low-density lipoprotein (LDL). This could be due to the blockade of IL-6 receptor and the role of IL-6 in inducing liver apolipoprotein expression (24,25). Whether TCZ-induced hyperlipemia may adversely affect the course of GO depends largely on the duration of treatment, and therefore, longterm studies are required to draw safe conclusions.…”

Clinical Value of IL6R Gene Variants as Predictive Biomarkers for Toxicity to Tocilizumab in Patients with Rheumatoid Arthritis

“…Additionally, in line with our results, in 2017, Arguinano et al described an association between rs4845625*T and high levels of LDL in a healthy cohort, suggesting that IL6R genetic variations may constitute a cardiovascular risk factor [ 36 ]. Although it seems that genotypes associated with better efficacy outcomes are also related to greater rates of dyslipidemia, this should not be problematic from a treatment biomarker perspective, given that dyslipidemia secondary to tocilizumab treatment has not been linked to cardiovascular events [ 40 , 41 , 42 , 43 , 44 , 45 ]. In fact, the association between the inflammatory burden in RA with changes in the lipid profile and cardiovascular risk has been described as the “lipid paradox”, as lower cholesterol is associated with higher cardiovascular risk in RA untreated patients [ 46 ].…”

“…In fact, the association between the inflammatory burden in RA with changes in the lipid profile and cardiovascular risk has been described as the “lipid paradox”, as lower cholesterol is associated with higher cardiovascular risk in RA untreated patients [ 46 ]. Although the mechanism underlying tocilizumab effects on the lipid profile is unclear, it has been demonstrated that, in a proinflammatory state with the activation of IL-6 pathways, there is a lowering of serum lipids mediated by the modification of apolipoprotein synthesis [ 47 ] as well as IL-6 local effects on fat tissue and muscle [ 44 ]. It has also been hypothesized that tocilizumab treatment raises lipid levels by reversing the lowering of lipid levels induced by IL-6-mediated inflammation [ 47 , 48 ].…”

“…It has also been hypothesized that tocilizumab treatment raises lipid levels by reversing the lowering of lipid levels induced by IL-6-mediated inflammation [ 47 , 48 ]. Another suggested explanation is that dyslipidemia is mediated by the direct effect of IL-6 levels, raised through the blockage of IL-6R on administering tocilizumab [ 44 ].…”