HDL biology
Tofacitinib raises CETP and atherogenic lipids in rheumatoid arthritis patients naive to prior biologic therapy (J Clin Lipidol 2025)
Original title: Modifications on lipid profile and high-density lipoprotein function related to treatment with tofacitinib in female patients with rheumatoid arthritis: Impact of previous therapy with biological agents
Thirty female rheumatoid arthritis patients starting the Janus kinase inhibitor tofacitinib were assessed at baseline and after 3 months for lipid profile, oxidized LDL, paraoxonase 1, lipoprotein-associated phospholipase A2, CETP, and HDL composition and function. Overall, total cholesterol, HDL cholesterol, non-HDL cholesterol and HDL capacity to acquire free cholesterol from triglyceride-rich lipoproteins increased after tofacitinib, while cholesterol efflux capacity was unchanged. Patients naive to prior biologic therapy (n equals 11) showed atherogenic increases in total cholesterol, LDL cholesterol, non-HDL cholesterol, apolipoprotein B, lipoprotein-associated phospholipase A2, and CETP after tofacitinib, alongside a beneficial rise in paraoxonase 1 activity, whereas patients previously treated with biological agents (n equals 19) showed no significant lipid changes, suggesting prior biologic therapy confers a more favourable cardiovascular lipid profile during tofacitinib treatment.
Original abstract
Background: Tofacitinib, a Janus kinase inhibitor, has been associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study evaluated tofacitinib's effects on lipid parameters and the impact of prior biological agents' therapy in RA patients.
Methods: Thirty female RA patients starting tofacitinib were assessed at baseline and after 3 months. Clinical assessments, health assessment questionnaire (HAQ), disease activity score 28 (DAS28), inflammatory markers, lipid profile, oxidized low-density lipoprotein (LDL), activities of paraoxonase 1 (PON 1), lipoprotein-associated phospholipase A2 (Lp-PLA2), cholesteryl ester transfer protein (CETP), high-density lipoprotein (HDL) composition, and HDL functions (cholesterol efflux and free cholesterol uptake from triglyceride-rich lipoproteins [TGRL]) upon lipolysis were measured.
Results: After 3 months, HAQ and DAS28 scores improved significantly. Total cholesterol (TC), HDL-C, non-HDL-C, and HDL capacity to acquire free cholesterol from TGRL increased, while enzyme activities and cholesterol efflux capacity remained unchanged. At baseline, patients with prior biological therapy (n = 19) had lower triglycerides, TC, non-HDL-C, and apolipoprotein (apo) B compared to biologic-naïve patients (n = 11). This group exhibited no lipid changes after tofacitinib, whereas biologic-naïve patients showed atherogenic increases in TC, LDL-C, non-HDL-C, apo B, Lp-PLA2, and CETP, alongside beneficial increases in PON 1 activity.
Conclusion: Tofacitinib improved disease activity and functional status in RA patients with minimal lipid changes. Patients previously treated with biological agents experienced no significant lipid alterations, while biologic-naïve patients showed atherogenic lipid changes and increased PON 1 activity. Prior biologic therapy may confer a more favorable CV profile before and after tofacitinib treatment.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.