背景/目的：Janus激酶抑制剂（JAKi）托法替尼（TOFA）、巴瑞替尼（BARI）、乌帕替尼（UPA）和非戈替尼（FILGO）是治疗类风湿关节炎的有效药物。然而，美国食品药品监督管理局（FDA）在批准TOFA后却对TOFA的安全性提出了担忧。这促使欧洲药品管理局 (EMA) 发布了两项限制 TOFA 使用的安全警告，然后向所有存在发生严重不良反应 (SAE) 高风险的 JAKi 患者发出了第三次警告。这些包括血栓形成、主要不良心脏事件 (MACE) 和癌症。这项工作的目的是分析 EMA 的前两个安全警告如何影响意大利风湿病学家开出 JAKi 的处方。方法：考虑2019年7月1日至2022年6月30日36个月内首次服用JAKi的所有类风湿关节炎患者。数据来自 29 个意大利三级转诊风湿病中心的医疗记录。根据 JAKi 处方是否发生在 EMA 第一次安全警报之前（2019 年 7 月 1 日至 10 月 31 日，第 1 组）、第一次和第二次警报之间（2019 年 11 月 1 日至 2 月 29 日），患者被分为三组，每组 4 个月2020 年，第 2 组），或第二次和第三次警报之间（2021 年 3 月 1 日至 2021 年 6 月 30 日，第 3 组）。分析了服用个体 JAKi 的患者的百分比和绝对变化。还评估了三组患者在人口统计学和临床​​特征方面的差异。结果：在整个研究期间，共有 864 名患者接受了 JAKi 处方。其中，第 1 组有 343 例，第 2 组有 233 例，第 3 组有 288 例。观察到，第 1 组和第 2 组之间服用 JAKi 的患者数量绝对减少了 32%，第 1 组和第 2 组之间则减少了 16%。第 3 组。相比之下，第 2 组和第 3 组患者的 JAKi 处方增加了 19%。在第一组中，BARI 是处方最多的药物（227 份处方，占总数的 66.2%），其次是TOFA (115, 33.5%) 和 UPA (1, 0.3%)。在第二组中，使用最多的 JAKi 是 BARI（147 例，63.1%），其次是 TOFA（65 例，27.9%）和 UPA（33 例，11.5%）。在第三组中，BARI 仍然是开出最多处方的 JAKi（104 处方，占 36.1%），其次是 UPA（89 处方，占 30.9%）、FILGO（89 处方，占 21.5%）和 TOFA（33 处方，占 11.5%）。在第 1 组和第 2 组之间以及第 2 组和第 3 组之间，接受 TOFA 治疗的患者数量显着减少 (p ˂ 0.01)。在第 1 组和第 2 组之间以及第 2 组和第 3 组之间，接受 BARI 治疗的患者人数显着减少 (p ˂ 0.01)。相比之下，第 2 组和第 3 组之间接受 UPA 治疗的患者数量有所增加 (p ˂ 0.01)。结论：这些数据表明，在对 TOFA 发出警告后，JAKi 处方总量有所减少。然而，处方医生认为更具选择性的 JAKi（UPA 和 FILGO）在风险/效益比方面是有利的，并且它们的使用逐渐增加，但以牺牲其他分子为代价。

Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA's first safety alert (1 July-31 October 2019, Group 1), between the first and second alerts (1 November 2019-29 February 2020, Group 2), or between the second and third alerts (1 March 2021-30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.