Park Sunny, Kim Min Kyu, Park Sung Bin, Kim Dong Hyeok, Byun Young Joo, Choi Soo An
Research Institute of Pharmaceutical Sciences, Korea University, Sejong 339-770, Republic of Korea.
College of Pharmacy, Korea University, Sejong 339-770, Republic of Korea.
Pharmaceuticals (Basel). 2025 Mar 11;18(3):394. doi: 10.3390/ph18030394.
Janus kinase (JAK) inhibitors are a new class of targeted therapies that block cytokines and the signal transduction and activators of transcription (STAT) pathway. However, post-marketing surveillance studies have led to revised recommendations, highlighting potential serious heart-related events and cancer risk of JAK inhibitors. Here, we aimed to determine the neurological adverse events (AEs) of JAK inhibitors (tofacitinib, ruxolitinib, and baricitinib) based on a global real-world database. We analyzed individual case safety reports from the Uppsala Monitoring Center from January 1968 to 4 April 2022. A disproportionality analysis was performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) to detect signals. Signals were classified according to the hierarchy of the Medical Dictionary for Regulatory Activities (MedDRA). Additionally, a stratified disproportionality analysis by age group and sex was performed for major AEs. A total of 30,051,159 reports for all drugs were analyzed in this study. Among 105,798 reports of tofacitinib, 14.1% (14,863 reports) were neurological AEs. For ruxolitinib and baricitinib, 14.5% (6317 reports) and 10.2% (1216 reports) were neurological AEs, respectively. Various neurological AE signals were detected for tofacitinib and ruxolitinib, with memory impairment exhibiting the highest number of reports and a positive signal in the stratified disproportionality analysis by age group. Baricitinib did not reach the signal detection threshold. This study suggests the potential for neurological AEs, including memory impairment, associated with tofacitinib and ruxolitinib use based on a real-world database.
Janus激酶（JAK）抑制剂是一类新型的靶向治疗药物，可阻断细胞因子以及信号转导和转录激活因子（STAT）通路。然而，上市后监测研究导致了建议的修订，突出了JAK抑制剂潜在的严重心脏相关事件和癌症风险。在此，我们旨在基于一个全球真实世界数据库确定JAK抑制剂（托法替布、鲁索替尼和巴瑞替尼）的神经系统不良事件（AE）。我们分析了乌普萨拉监测中心1968年1月至2022年4月4日的个体病例安全报告。使用比例报告比（PRR）、报告比值比（ROR）和信息成分（IC）进行不成比例分析以检测信号。信号根据《监管活动医学词典》（MedDRA）的层次结构进行分类。此外，对主要不良事件按年龄组和性别进行分层不成比例分析。本研究共分析了所有药物的30,051,159份报告。在105,798份托法替布报告中，14.1%（14,863份报告）为神经系统不良事件。对于鲁索替尼和巴瑞替尼，分别有14.5%（6317份报告）和10.2%（1216份报告）为神经系统不良事件。托法替布和鲁索替尼检测到了各种神经系统不良事件信号，其中记忆障碍报告数量最多，且在按年龄组进行的分层不成比例分析中呈阳性信号。巴瑞替尼未达到信号检测阈值。这项基于真实世界数据库的研究表明，使用托法替布和鲁索替尼可能会出现包括记忆障碍在内的神经系统不良事件。
