Makris Anastasios, Barkas Fotios, Sfikakis Petros P, Liberopoulos Evangelos, Agouridis Aris P
School of Medicine, European University Cyprus, Nicosia 2404, Cyprus.
Department of Hygiene & Epidemiology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece.
J Clin Med. 2022 Nov 22;11(23):6894. doi: 10.3390/jcm11236894.
Our aim was to systematically investigate the effect of upadacitinib, an oral JAK-1 selective inhibitor, on lipid profile and cardiovascular disease risk.
PubMed, PubMed Central and ClinicalTrials.gov databases were searched for relevant randomized controlled trials (RCTs) up to 31 July 2022. We performed a qualitative synthesis of published RCTs to investigate the associations of upadacitinib with lipoprotein changes, along with a quantitative synthesis of MACE and mean lipoprotein changes where there were available data.
Nineteen RCTs were eligible for the present systematic review, which included 10,656 patients with a mean age of 51 years and a follow-up period of 12-52 weeks. Increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were noted upon upadacitinib administration (3-48 mg/day) in 15 studies, while the LDL-C:HDL-C ratio remained unchanged. The pooled analyses of three placebo-controlled RCTs ( = 2577) demonstrated that upadacitinib at 15 mg increased the LDL-C by 15.18 mg/dL (95% CI: 7.77-22.59) and HDL-C by 7.89 mg/dL (95% CI: 7.08-8.69). According to the pooled analysis of 15 placebo-controlled RCTs ( = 7695), upadacitinib had no effect on MACE (risk ratio, RR: 0.62; 95% CI: 0.24-1.60). A sub-analysis focusing on upadacitinib at 15 mg (12 studies, = 5395) demonstrated similar results (RR: 0.67; 95% CI: 0.19-2.36).
Treatment with upadacitinib increases both LDL-C and HDL-C levels. Nevertheless, upadacitinib had no significant effect on the cardiovascular disease risk during a ≤52-week follow-up.
我们的目的是系统地研究口服JAK-1选择性抑制剂乌帕替尼对血脂谱和心血管疾病风险的影响。
检索了截至2022年7月31日的PubMed、PubMed Central和ClinicalTrials.gov数据库中的相关随机对照试验（RCT）。我们对已发表的RCT进行了定性综合分析，以研究乌帕替尼与脂蛋白变化之间的关联，并在有可用数据的情况下对主要不良心血管事件（MACE）和平均脂蛋白变化进行了定量综合分析。
19项RCT符合本系统评价的标准，共纳入10656例患者，平均年龄51岁，随访期为12至52周。在15项研究中，给予乌帕替尼（3至48毫克/天）后，低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）均升高，而LDL-C与HDL-C的比值保持不变。三项安慰剂对照RCT（n = 2577）的汇总分析表明，15毫克剂量的乌帕替尼使LDL-C升高15.18毫克/分升（95%可信区间：7.77至22.59），HDL-C升高7.89毫克/分升（95%可信区间：7.08至8.69）。根据15项安慰剂对照RCT（n = 7695）的汇总分析，乌帕替尼对MACE无影响（风险比，RR：0.62；95%可信区间：0.24至1.60）。一项针对15毫克剂量乌帕替尼的亚组分析（12项研究，n = 5395）显示了类似结果（RR：0.67；95%可信区间：0.19至2.36）。
乌帕替尼治疗可使LDL-C和HDL-C水平均升高。然而，在≤52周的随访期间，乌帕替尼对心血管疾病风险无显著影响。
