Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase IIb Study of Patients With Active Rheumatoid Arthritis
Effects of Baricitinib on Lipid, Apolipoprotein, and Lipoprotein Particle Profiles in a Phase IIb Study of Patients With Active Rheumatoid Arthritis
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DOI：
10.1002/art.40036
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发表时间：
2017-05-01
影响因子：
13.3
通讯作者：
Macias, William L.
中科院分区：
文献类型：
--
作者：
Kremer, Joel M.;Genovese, Mark C.;Macias, William L.
目标。评估巴西替尼对中重度类风湿关节炎患者血脂的影响。在301名随机患者中研究了每日一次的baricitinib（1,2,4或8mg）或安慰剂治疗。在第12周和第24周评估脂质谱、脂蛋白颗粒大小和颗粒数量的变化，并评估与临床疗效的关系。在第4周和第12周对安慰剂组、4 mg和8 mg巴西替尼组的载脂蛋白进行了评估。baricitinib治疗导致从基线到第12周的血脂水平呈剂量依赖性升高（低密度脂蛋白[LDL]胆固醇在1 mg和8 mg治疗组分别增加3.4 mg/dl和11.8 mg/dl；高密度脂蛋白[HDL]胆固醇分别增加3.3 mg/dl和8.1 mg/dl；甘油三酯分别增加6.4 mg/dl和15.4 mg/dl）。LDL胆固醇的组平均升高与大LDL颗粒的平均升高和小密度LDL颗粒的平均降低一致。从基线到第12周，4 mg baricitinib组（分别为9.5%、6.8%和23.0%）和8 mg baricitinib组（分别为12.2%、7.1%和19.7%）的载脂蛋白A-I、载脂蛋白B和载脂蛋白CIII增加，ldl相关载脂蛋白CIII没有增加（4 mg baricitinib组-4.5%；8 mg baricitinib组-9.0%）。Baricitinib在给药4mg（236.0%）和8mg（232.0%）时降低hdl相关血清淀粉样蛋白A；仅在8毫克剂量下观察到脂蛋白(A)的显著降低（216.6%）。第12周HDL胆固醇升高与疾病活动评分和简化疾病活动指数改善相关；总胆固醇、低密度脂蛋白胆固醇和甘油三酯的变化没有显示出类似的关系。在这项研究中观察到baricitinib相关的血脂水平升高。高密度脂蛋白胆固醇水平的升高与临床结果的改善相关。
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 4mg (236.0%) and 8mg (232.0%); a significant reduction in lipoprotein (a) was observed only with 8-mg doses (216.6%). 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.