Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase 2b Study in Patients with Active Rheumatoid Arthritis
In this analysis of the effect of baricitinib on changes in lipid profile, lipoprotein particle size and apolipoprotein content, increases in serum lipids were observed with HDL-C increases correlating with improved clinical outcomes.
Eligible patients (N=301) met the inclusion criteria for the Phase 2b randomised, double-blind, placebo-controlled study.1 Patients were assigned in a 2:1:1:1:1 ratio to once-daily doses of placebo or baricitinib 1, 2, 4, or 8 mg, respectively. Those receiving 2 mg, 4 mg, or 8 mg remained on treatment for a further 12 weeks.
Increases in LDL-C, HDL-C, triglycerides and total cholesterol were observed with baricitinib treatment as early as Week 2, and were dose-dependent over time. HDL-C increases were significantly correlated with an improvement in DAS28-CRP score.
Previously, increases in small LDL particle number have been associated with an increased risk of cardiovascular (CV) events. In the current analysis, although total LDL increased, baricitinib did not change the total particle number. Instead, in the 2-, 4- and 8 mg baricitinib groups there was a statistically significant increase in the number of large LDL particles at Week 12 (and Week 24 for 2 mg), and a reduction in the number of medium-small and very-small LDL particles at Week 24 for the 4- and 8 mg groups.
In order to understand the clinical impact of these findings, long-term observational studies are needed to track actual CV events in patients taking baricitinib.
1. Keystone EC, et al. Ann Rheum Dis 2015;74:333–40.