Tocilizumab enhances HDL functionality in rheumatoid arthritis: A 6-month prospective study on cardiovascular risk modulation

BACKGROUND Rheumatoid arthritis (RA) confers elevated cardiovascular risk, partly driven by dysfunctional lipoproteins and oxidative stress. Interleukin-6 (IL-6) inhibition with tocilizumab may modify lipid profiles and enhance high-density lipoprotein (HDL) functionality, potentially influencing cardiometabolic risk. OBJECTIVE To evaluate the impact of IL-6 receptor blockade with tocilizumab on lipid profile and HDL functionality in patients with RA over a 6-month follow-up. METHODS Prospective observational study in 16 female patients with RA initiating tocilizumab treatment. Assessments were conducted at baseline and 6 months. Clinical activity (Disease Activity Score in 28, Health Assessment Questionnaire [HAQ]), inflammatory markers, lipid profile, lipoprotein(a) [Lp(a)], oxidized low-density lipoprotein (oxLDL), paraoxonase-1 activities (PON and ARE), cholesteryl ester transfer protein (CETP) activity, HDL cholesterol efflux capacity, and HDL free-cholesterol uptake during triglyceride-rich lipoprotein (TGRL) lipolysis were measured. RESULTS Tocilizumab significantly reduced disease activity and inflammation, with 87% of patients achieving remission and improved HAQ scores. Total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and HDL-C increased, whereas Lp(a) decreased. HDL functional metrics improved: cholesterol efflux capacity rose by ∼16%, and free-cholesterol uptake from TGRL lipolysis increased by ∼40% (P < .05). CETP activity decreased by ∼22%. Antioxidant properties improved, with PON and ARE activities increasing by ∼12% and ∼11%, respectively, and oxLDL decreasing by ∼11%. CONCLUSION After 6 months of IL-6 blockade, patients exhibited profound suppression of inflammation and enhanced HDL cardioprotective functions despite rises in LDL-C. Improvements in cholesterol efflux, TGRL-cholesterol handling, and antioxidant activity suggest a shift toward more favorable lipoprotein quality. Long-term and randomized studies are needed to determine whether these mechanistic changes translate into reduced cardiovascular events.