口服Janus激酶抑制剂（JAKi）代表了治疗类风湿性关节炎（RA）的有效策略。一项针对具有既往风险的患者的最新研究支持，托法替尼与肿瘤坏死因子α抑制剂相比，与心血管和肿瘤发生率更高相关。鉴于这些数据与实际经验之间的明显差异，我们旨在调查可用JAKi的安全性和疗效，以多中心队列研究为基础的回顾性评估了米兰，意大利的四家三级综合医院的RA患者，这些患者曾接受过一种JAKi（托法替尼、巴利西替尼、乌帕西替尼、费尔戈替尼）。记录了与JAKi安全性相关的结果，特别是主要心血管事件以及特殊兴趣不良事件（AESI），包括严重感染、机会性感染、静脉血栓栓塞、带状疱疹感染、肝损伤、恶性肿瘤和死亡以及计算了保留率。进一步分析包括符合影响托法替尼安全性的风险因素的患者。共纳入685例患者，并给予巴利西替尼（48％），托法替尼（31％），乌帕西替尼（14％）或费尔戈替尼（7％），其中有47％是在生物学治疗之前作为首次创新治疗。在共1,137人年的观察中，我们记录了1例中风，123例（18％）AESI，包括3例由严重感染引起的死亡。在有较高心血管风险的患者中，我们观察到特殊兴趣不良事件的发生率较高（23％）。我们的实际数据证实JAKi具有高效和低AESI风险，并且特别是在基线不显示心血管风险因素的患者中。我们的研究未能确定分子间的差异，不同的概况应在更大的前瞻性队列中确定。

Oral Janus kinase inhibitors (JAKi) represent an effective strategy for rheumatoid arthritis (RA) treatment. A recent study on patients with a pre-existing risk supported that tofacitinib is associated with higher incidence of cardiovascular and neoplastic events compared to Tumor Necrosis Factor α inhibitors. Given the apparent discrepancy between these data and real-life experience we aimed to investigate the safety and efficacy of the available JAKi in a multicenter cohort.We retrospectively evaluated patients with RA who ever received one JAKi (tofacitinib, baricitinib, upadactinib, filgotinib) from four tertiary care centers in Milan, Italy. Outcomes related to JAKi safety were recorded, particularly as major cardiovascular events as well as adverse events of special interest (AESI) which included serious infections, opportunistic infections, venous thrombo-embolism, herpes zoster infections, liver injury, malignancies, and deaths while retention rates were also calculated. Further analyses included patients fulfilling the risk factors suggested to influence tofacitinib safety.Six hundred-eighty-five patients were included and received baricitinib (48%), tofacitinib (31%), upadacitinib (14%), or filgotinib (7%), in 47% as first-line innovative treatment prior to a biologic. Out of a total of 1137 patient-years of observation, we recorded 1 stroke, 123 (18%) AESI, including 3 deaths, all due to severe infections. Among patients with a higher cardiovascular risk, we observed a higher frequency of adverse events of special interest (23%).Our real-life data confirm that JAKi are effective and carry a low risk of AESI, especially in patients that do not display cardiovascular risk factors at baseline. Our study could not identify differences between molecules and different profiles should be defined in larger prospective cohorts.