Botnar Research Centre, Nuffield Department ofOrthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Center for Rheumatology, Albany Medical College, Albany, New York, USA.
Ann Rheum Dis. 2018 Jul;77(7):988-995. doi: 10.1136/annrheumdis-2017-212461. Epub 2018 Feb 20.
Lipid profiles are altered by active disease in patients with rheumatoid arthritis (RA) and may be further modified by treatment with Janus kinase inhibitors and other disease-modifying antirheumatic drugs.
Lipid data were analysed from phase II and III studies of 4 mg (n=997) and 2 mg (n=479) oral baricitinib administered once daily in patients with moderate-to-severe active RA. Lipoprotein particle size and number and GlycA were evaluated with nuclear magnetic resonance in one phase III study. The effect of statin therapy on lipid levels was evaluated in patients on statins at baseline and in patients who initiated statins during the study.
Treatment with baricitinib was associated with increased levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides, but no significant change in LDL-C:HDL-C ratio. Lipid levels plateaued after 12 weeks of treatment. Baricitinib treatment increased large LDL and decreased small, dense LDL particle numbers and GlycA. Lipid changes from baseline were not significantly different between baseline statin users and non-users. In patients who initiated statin therapy during the study, LDL-C, triglycerides (baricitinib 4 mg only) and apolipoprotein B decreased to pre-baricitinib levels; HDL-C and apolipoprotein A-I levels remained elevated.
Baricitinib was associated with increased LDL-C, HDL-C and triglyceride levels, but did not alter the LDL-C:HDL-C ratio. Evaluation of cardiovascular event rates during long-term treatment is warranted to further characterise these findings and their possible clinical implications.
NCT00902486, NCT01469013, NCT01185353, NCT01721044, NCT01721057, NCT01711359, NCT01710358, NCT01885078.
类风湿关节炎（RA）患者的脂谱会因疾病活动而改变，而使用 Janus 激酶抑制剂和其他疾病修正抗风湿药物治疗可能会进一步改变。
分析了 4mg（n=997）和 2mg（n=479）每日口服一次巴利昔替尼治疗中重度活动期 RA 患者的 II 期和 III 期研究中的脂质数据。在一项 III 期研究中，使用磁共振评估脂蛋白颗粒大小和数量及 GlycA。评估了他汀类药物治疗对基线时使用他汀类药物的患者和研究期间开始使用他汀类药物的患者的血脂水平的影响。
巴利昔替尼治疗与总胆固醇、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯水平升高相关，但 LDL-C：HDL-C 比值无显著变化。治疗 12 周后，血脂水平趋于稳定。巴利昔替尼治疗增加了大 LDL，减少了小而密 LDL 颗粒数和 GlycA。基线时使用他汀类药物和未使用他汀类药物的患者，从基线到治疗结束的脂质变化无显著差异。在研究期间开始使用他汀类药物的患者中，LDL-C、甘油三酯（仅巴利昔替尼 4mg）和载脂蛋白 B 降低至巴利昔替尼治疗前水平；HDL-C 和载脂蛋白 A-I 水平仍升高。
巴利昔替尼与 LDL-C、HDL-C 和甘油三酯水平升高相关，但不改变 LDL-C：HDL-C 比值。需要进行长期治疗的心血管事件发生率评估，以进一步描述这些发现及其可能的临床意义。
NCT00902486、NCT01469013、NCT01185353、NCT01721044、NCT01721057、NCT01711359、NCT01710358、NCT01885078。
