Shi Lin-Hong, Wei James Cheng-Chung, Tung William Tao-Hsin
The Jockey Club School of Public Health and Primary Care, The Prince of Wales Hospital, The Chinese University of Hong Kong, New Territories, Hong Kong, China.
Department of Allergy, Immunology and Rheumatology, Institute of Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Rheumatol Ther. 2025 Jul 19. doi: 10.1007/s40744-025-00783-5.
Our objective was to evaluate the comparative effects of five Janus kinase inhibitors (JAKis) with ten interventions, comparing their impact on major adverse cardiovascular events (MACE) and thromboembolism events (TE) in patients with psoriatic arthritis (PsA) through network meta-analysis (NMA).
We conducted a search across four databases from inception to September 30, 2024. We also included studies comparing JAKis with placebo or TNFi in adults (≥ 18 years) with PsA. The primary outcomes were the incidence of MACE and TE. We used network meta-analysis with random effects to estimate summary risk ratios (RRs).
Eleven studies met the eligibility criteria. Combined RCT and LTE data showed 23 MACE and 26 TE events, with incidence rates (IR) of 0.25 and 0.29 per 100 person-years for MACE and TE, respectively. Across all RCT data, there were 12 MACE and 8 TE events, with IRs of 0.62 and 0.41 per 100 person-years for MACE and TE, respectively. In eligible RCTs, tofacitinib (5 mg and 10 mg) and upadacitinib (30 mg) were associated with a lower risk of TE compared to placebo (GRADE certainty: moderate, moderate, and high, respectively). Compared to adalimumab, upadacitinib (15 mg and 30 mg) was associated with a decreased risk of MACE in RCT/LTE data (GRADE certainty: moderate and moderate, respectively).
Tofacitinib and upadacitinib are superior to placebo and comparable to adalimumab regarding MACE and TE risk, even with long-term exposure, which may be positively considered in PsA treatment. The cardiovascular safety of new investigational JAKis needs further validation.
我们的目标是通过网络荟萃分析（NMA）评估五种Janus激酶抑制剂（JAKis）与十种干预措施的比较效果，比较它们对银屑病关节炎（PsA）患者主要不良心血管事件（MACE）和血栓栓塞事件（TE）的影响。
我们对四个数据库进行了从起始到2024年9月30日的检索。我们还纳入了比较JAKis与安慰剂或肿瘤坏死因子抑制剂（TNFi）在成年（≥18岁）PsA患者中的研究。主要结局是MACE和TE的发生率。我们使用随机效应的网络荟萃分析来估计汇总风险比（RRs）。
十一项研究符合纳入标准。综合随机对照试验（RCT）和长期扩展（LTE）数据显示有23例MACE事件和26例TE事件，MACE和TE的发生率分别为每100人年0.25和0.29。在所有RCT数据中，有12例MACE事件和8例TE事件，MACE和TE的发生率分别为每100人年0.62和0.41。在符合条件的RCT中，与安慰剂相比，托法替布（5毫克和10毫克）和乌帕替尼（30毫克）与较低的TE风险相关（GRADE确定性：分别为中等、中等和高）。在RCT/LTE数据中，与阿达木单抗相比，乌帕替尼（15毫克和30毫克）与较低的MACE风险相关（GRADE确定性：分别为中等和中等）。
托法替布和乌帕替尼在MACE和TE风险方面优于安慰剂且与阿达木单抗相当，即使长期使用，这在PsA治疗中可能会被积极考虑。新型研究性JAKis的心血管安全性需要进一步验证。
