Li Na, Gou Zhong-Ping, Du Shuang-Qing, Zhu Xiao-Hong, Lin Hui, Liang Xiu-Fang, Wang Yong-Sheng, Feng Ping
National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, Institute of Clinical Trial Center, West China Hospital, Sichuan University, Sichuan, 610041, Chengdu, China.
Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Clin Rheumatol. 2022 Mar;41(3):677-688. doi: 10.1007/s10067-021-06003-z. Epub 2022 Jan 7.
Janus kinase (JAK) inhibitors are a new class of medication for treatment of rheumatoid arthritis (RA), and such inhibitors alter levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in RA patients. However, the extent of such changes has not been systematically reviewed.
A systematic review and network meta-analysis was performed on randomized trials in RA patients in response to JAKi identified from Pubmed, Medline, Embase, and Cochrane Controlled Trials Register. The primary outcome was mean change of HDL-C and LDL-C from baseline. Mean treatment differences and the rank of the effect of various JAKi on HDL-C and LDL-C were estimated.
Based on data from 18 unique studies involving five approved JAK inhibitors and 6697 RA patients (JAKi = 3341, placebo = 3356), such inhibitors led to a mean increase of 8.11 mg/dl (95% CI 6.65-9.58, I = 82%) in HDL levels from baseline, and a mean increase of 11.37 mg/dl (95% CI 7.84-14.91, I = 88%) in LDL levels from baseline. Cardiovascular disease risk did not differ significantly between patients who received JAK inhibitors or those who received placebo or active agents.
Our analysis suggests that, at their recommended doses, all five JAK inhibitors lead to an increase in HDL and LDL levels in RA patients. Further long-term research is required to extend these results and understand whether changes in lipid levels in RA patients can affect cardiovascular risk. Key Points • This is the first systematic review and NMA examining the effect of all five clinically approved JAK inhibitors on lipid levels in RA patients. • Recommended doses of JAK inhibitors used for the treatment of RA patients can induce a significant increase in HDL and LDL levels. • Indirect pairwise comparisons suggest that only upadacitinib and peficitinib have significantly different ability to induce LDL change in RA patients.
Janus激酶（JAK）抑制剂是一类用于治疗类风湿关节炎（RA）的新型药物，此类抑制剂会改变RA患者的高密度脂蛋白（HDL）和低密度脂蛋白（LDL）水平。然而，这种变化的程度尚未得到系统评价。
对从PubMed、Medline、Embase和Cochrane对照试验注册库中识别出的关于RA患者使用JAK抑制剂的随机试验进行系统评价和网状Meta分析。主要结局是HDL-C和LDL-C相对于基线的平均变化。估计了平均治疗差异以及各种JAK抑制剂对HDL-C和LDL-C影响的排序。
基于18项涉及5种已批准的JAK抑制剂和6697例RA患者的独立研究数据（JAK抑制剂组=3341例，安慰剂组=3356例），此类抑制剂使HDL水平相对于基线平均升高8.11mg/dl（95%CI 6.65-9.58，I²=82%），使LDL水平相对于基线平均升高11.37mg/dl（95%CI 7.84-14.91，I²=88%）。接受JAK抑制剂治疗的患者与接受安慰剂或活性药物治疗的患者之间的心血管疾病风险无显著差异。
我们的分析表明，在推荐剂量下，所有5种JAK抑制剂都会使RA患者的HDL和LDL水平升高。需要进一步的长期研究来扩展这些结果，并了解RA患者血脂水平的变化是否会影响心血管风险。要点 • 这是第一项系统评价和网状Meta分析，研究了所有5种临床批准的JAK抑制剂对RA患者血脂水平的影响。 • 用于治疗RA患者的JAK抑制剂推荐剂量可导致HDL和LDL水平显著升高。 • 间接成对比较表明，只有乌帕替尼和培非替尼在诱导RA患者LDL变化方面的能力有显著差异。
