Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase IIb Study of Patients With Active Rheumatoid Arthritis.

Autor: Kremer JM; Albany Medical College, Albany, New York., Genovese MC; Stanford University Medical Center, Palo Alto, California., Keystone E; University of Toronto, Toronto, Ontario, Canada., Taylor PC; University of Oxford, Oxford, UK., Zuckerman SH; Eli Lilly and Company, Indianapolis, Indiana., Ruotolo G; Eli Lilly and Company, Indianapolis, Indiana., Schlichting DE; Eli Lilly and Company, Indianapolis, Indiana., Crotzer VL; Eli Lilly and Company, Indianapolis, Indiana., Nantz E; Eli Lilly and Company, Indianapolis, Indiana., Beattie SD; Eli Lilly and Company, Indianapolis, Indiana., Macias WL; Eli Lilly and Company, Indianapolis, Indiana.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2017 May; Vol. 69 (5), pp. 943-952.
DOI: 10.1002/art.40036
Abstrakt: Objective: To assess the effects of baricitinib on lipid profiles in patients with moderate-to-severe rheumatoid arthritis.
Methods: Treatment with once-daily doses of baricitinib (1, 2, 4, or 8 mg) or placebo was studied in 301 randomized patients. Changes in lipid profile and lipoprotein particle size and particle number were assessed at weeks 12 and 24, and associations with clinical efficacy were evaluated. Apolipoproteins were assessed at weeks 4 and 12 in the placebo group and the 4-mg and 8-mg baricitinib groups.
Results: Treatment with baricitinib resulted in dose-dependent increases in serum lipid levels from baseline to week 12 (low-density lipoprotein [LDL] cholesterol increases of 3.4 mg/dl and 11.8 mg/dl in the 1 mg and 8 mg treatment groups, respectively; high-density lipoprotein [HDL] cholesterol increases of 3.3 mg/dl and 8.1 mg/dl, respectively; triglycerides increases of 6.4 mg/dl and 15.4 mg/dl, respectively). Group-wise mean increases in LDL cholesterol were coincident with mean increases in large LDL particles and mean reductions in small dense LDL particles. Increases from baseline to week 12 in apolipoprotein A-I, apolipoprotein B, and apolipoprotein CIII were observed with 4-mg doses of baricitinib (9.5%, 6.8%, and 23.0%, respectively) and with 8-mg doses (12.2%, 7.1%, and 19.7%, respectively), with no increase in LDL-associated apolipoprotein CIII (-4.5% with 4-mg baricitinib; -9.0% with 8-mg baricitinib). Baricitinib reduced HDL-associated serum amyloid A when administered at 4 mg (-36.0%) and 8 mg (-32.0%); a significant reduction in lipoprotein (a) was observed only with 8-mg doses (-16.6%). Increased HDL cholesterol at week 12 correlated with improved Disease Activity Scores and Simplified Disease Activity Index; changes in total cholesterol, LDL cholesterol, and triglycerides did not reveal a similar relationship.
Conclusion: Baricitinib-associated increases in serum lipid levels were observed in this study. Increases in levels of HDL cholesterol correlated with improved clinical outcomes.
(© 2016, American College of Rheumatology.)
Databáze: MEDLINE
Externí odkaz: