Albany Medical College, Albany, New York.
Stanford University Medical Center, Palo Alto, California.
Arthritis Rheumatol. 2017 May;69(5):943-952. doi: 10.1002/art.40036.
To assess the effects of baricitinib on lipid profiles in patients with moderate-to-severe rheumatoid arthritis.
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.
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.
Baricitinib-associated increases in serum lipid levels were observed in this study. Increases in levels of HDL cholesterol correlated with improved clinical outcomes.
评估巴瑞替尼对中重度类风湿关节炎患者血脂谱的影响。
对 301 名随机患者进行了每日一次剂量的巴瑞替尼（1、2、4 或 8mg）或安慰剂治疗的研究。在第 12 周和第 24 周评估了血脂谱、脂蛋白颗粒大小和颗粒数的变化，并评估了与临床疗效的关系。在安慰剂组和 4mg 和 8mg 巴瑞替尼组中，在第 4 周和第 12 周评估了载脂蛋白。
巴瑞替尼治疗导致血清脂质水平从基线到第 12 周呈剂量依赖性升高（1mg 和 8mg 治疗组的低密度脂蛋白[LDL]胆固醇分别升高 3.4mg/dl 和 11.8mg/dl；高密度脂蛋白[HDL]胆固醇分别升高 3.3mg/dl 和 8.1mg/dl；甘油三酯分别升高 6.4mg/dl 和 15.4mg/dl）。组间 LDL 胆固醇的平均升高与大 LDL 颗粒的平均升高和小致密 LDL 颗粒的平均减少一致。用巴瑞替尼 4mg 剂量（分别为 9.5%、6.8%和 23.0%）和 8mg 剂量（分别为 12.2%、7.1%和 19.7%）观察到载脂蛋白 A-I、载脂蛋白 B 和载脂蛋白 CIII 从基线到第 12 周的升高，而 LDL 相关载脂蛋白 CIII 没有增加（4mg 巴瑞替尼为-4.5%；8mg 巴瑞替尼为-9.0%）。巴瑞替尼在 4mg（-36.0%）和 8mg（-32.0%）时降低了 HDL 相关血清淀粉样蛋白 A；仅在 8mg 剂量时观察到脂蛋白（a）显著降低（-16.6%）。第 12 周时 HDL 胆固醇的升高与改善的疾病活动评分和简化疾病活动指数相关；总胆固醇、LDL 胆固醇和甘油三酯的变化没有显示出类似的关系。
本研究观察到巴瑞替尼相关的血清脂质水平升高。HDL 胆固醇水平的升高与临床疗效的改善相关。
