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

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.

Keywords: Cardiovascular disease; HDL-associated enzymes; Lipoproteins; Rheumatoid arthritis; Tofacitinib.