Tofacitinib Can Improve Cardiovascular Health in Rheumatoid Arthritis Patients

Low cholesterol levels in patients with active rheumatoid arthritis (RA) may be controlled by increases in cholesterol ester catabolism, which can be reduced by tofacitinib, according to research published in Arthritis & Rheumatology.

A collaborative team of researchers conducted a phase 1 open label study across 7 centers in the United States in order to assess cholesterol and lipoprotein kinetics. The researchers used C cholesterol and C leucine infusions to evaluate RA patients after they received oral tofacitinib 10 mg twice daily for 6 weeks. Tofacitinib is an oral JAK inhibitor which controls intracellular signaling of various important cytokine receptors involved in the inflammatory cascade. The patients were 18 years or older with a body mass index < 35 mg/ m² who were not taking lipid regulating agents, hormonal forms of contraception, isotretinoin, and supplements containing plan t sterols/ stanols or cholestin. They were included in the study if they had active RA defined by ≥4 tender/painful joints and ≥4 swollen joints and various other criteria.

In the 36 RA patients, the researchers observed reduced levels of high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, total cholesterol, and apolipoprotein A-I (Apo A-I), and HDL cholesterol particle number than in the 33 healthy volunteers. The cholesterol ester fractional catabolic rate was higher in the RA patients than the healthy volunteers, the researchers commented. However, they did not find any differences in cholesterol ester transfer protein, cholesterol ester production rate, HDL associated Apo A-I fractional catabolic rate, or LDL associated Apo B fractional catabolic rate.

After the treatment of tofacitinib in the RA patients, the patients demonstrated decreased cholesterol ester fractional catabolic rates and increased cholesterol levels. The decrease in cholesterol ester fractional catabolic rate was associated significantly with the increase of HDL cholesterol, the authors wrote. Plus, the HDL cholesterol particle number increased and markers of HDL cholesterol function improved.

“This is the first study to assess cholesterol and lipoprotein kinetics in patients with active RA and matched healthy volunteers,” the authors concluded. “The data suggest that low cholesterol levels in patients with active RA may be driven by increases in cholesterol ester catabolism. Tofacitinib treatment reduced cholesterol ester catabolism, thereby increasing cholesterol levels toward those in healthy volunteers, and markers of antiatherogenic HDL function improved.”

The authors continued that these results warranted further investigation because RA patients have significantly increased cardiovascular morbidity and mortality compared to the general populations.