Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment

Abstract

Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients' lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p < 0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol's fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient's lipid profile in daily clinical practice.

Increased high molecular weight adiponectin and lean mass during tocilizumab treatment in patients with rheumatoid arthritis: a 12-month multicentre study

“…As expected and as previously reported [ 18 , 42 ], lipid parameters increased during TCZ treatment, especially total and LDL cholesterol without alteration of atherogenic index. However, these changes are complex and inflammation itself has a wide range of consequences on lipids, lipoproteins and associated molecules as exemplified by the lipid paradox [ 7 , 8 ].…”

Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components

“…[42][43][44] On the other hand, the association of DAS-28 and VLDL-C levels is not clear yet, but it has been reported that RA patients with high disease activity had alterations of the lipid profile. 38,45 Rheumatoid factor (RF) correlated with age and smoking index, which agrees with other reports [46][47][48] ; likewise, RF correlated with triglycerides, which could be explained by this autoantibody´s positive correlation with a high RA disease activity, 49 a status associated with lipids alteration.…”

Acute Hypertriglyceridaemia Caused by Tocilizumab in a Patient with Severe COVID-19

“…Treatment-related increases in circulating lipid levels have been observed during the long-term administration of TCZ in patients with rheumatoid arthritis (RA) ( 4 - 6 ). Cacciapaglia et al observed a significant increase in TG levels in 40 patients with RA treated with TCZ (TG, 139±13 mg/dL at baseline vs. 157±15 mg/dL at 24 weeks) compared with those in 20 RA patients who received methotrexate (TG, 126±26 mg/dL at baseline vs. 121±24 mg/dL at 24 weeks) during the first 24 weeks ( 4 ).…”

“…Treatment-related increases in circulating lipid levels have been observed during the long-term administration of TCZ in patients with rheumatoid arthritis (RA) ( 4 - 6 ). Cacciapaglia et al observed a significant increase in TG levels in 40 patients with RA treated with TCZ (TG, 139±13 mg/dL at baseline vs. 157±15 mg/dL at 24 weeks) compared with those in 20 RA patients who received methotrexate (TG, 126±26 mg/dL at baseline vs. 121±24 mg/dL at 24 weeks) during the first 24 weeks ( 4 ). According to Giles et al, in a randomised controlled trial comparing treatment with TCZ and etanercept for RA, patients administered TCZ showed a median increase of 13.6% and 11.1% in TG and LDL-C levels, respectively, compared to those in the etanercept arm at 4 weeks, demonstrating a significant increase ( 6 ).…”