Journal of clinical lipidology · 2026
Tocilizumab enhances HDL functionality in rheumatoid arthritis: A 6-month prospective study on cardiovascular risk modulation.
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Gómez Rosso Leonardo, Botta Eliana, Pierini Florencia, Martín Maximiliano, Soledad Sáez María, Davico Belén, Cerda Osvaldo, Citera Gustavo, Gandino Ignacio, Rosa Javier, Kontush Anatol, Soriano Enrique R, Brites Fernando
Аннотация
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.
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.