Data Sheet 1_Signal mining and analysis of ripretinib adverse events: a real-world pharmacovigilance analysis based on the FAERS database.docx

BackgroundRipretinib is a tyrosine kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumors (GISTs) who have previously received treatment with at least three kinase inhibitors. The objective of this study was to evaluate adverse events(AEs) associated with ripretinib using data from the FDA Adverse Event Reporting System (FAERS) database. MethodsIndividual case safety reports (ICSRs) related to of ripretinib from 2020 Q2 to 2024 Q2 were extracted from the FAERS database. This study used the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) for disproportionality analysis. In addition, this research also performed a descriptive analysis of the time-to-onset (TTO) of AEs related to ripretinib. ResultsA total of 3,513 ICSRs with ripretinib as the primary suspect (PS) were retrieved from the FAERS database. At the preferred term(PT) level, this study detected 116 positive AEs. Common AEs included alopecia, constipation, muscle spasms, dry skin, decreased appetite. Notably, unexpected AEs such as pleural mass, blood magnesium abnormal, blood potassium abnormal, hepatic lesion, and liver abscess were also observed. The median time to onset of ripretinib-related AEs was 102 days (29–254 days), with the majority of AEs occurring during the first month of treatment. ConclusionThis study identified some known AEs associated with ripretinib and discovered unexpected AEs, providing preliminary insights into its safety in the real world. This information is valuable for clinical monitoring and the safe use of ripretinib.背景：瑞普替尼（ripretinib）是一种酪氨酸激酶抑制剂（tyrosine kinase inhibitor），获批用于治疗既往接受过至少三种激酶抑制剂治疗的晚期胃肠道间质瘤（gastrointestinal stromal tumors, GISTs）成人患者。本研究旨在利用美国食品药品监督管理局不良事件报告系统（FDA Adverse Event Reporting System, FAERS）数据库数据，评估瑞普替尼相关的不良事件（adverse events, AEs）。 研究方法：从FAERS数据库中提取2020年第二季度至2024年第二季度期间与瑞普替尼相关的个例安全性报告（individual case safety reports, ICSRs）。本研究采用报告比值比（reporting odds ratio, ROR）、比例报告比值比（proportional reporting ratio, PRR）、贝叶斯置信传播神经网络（Bayesian confidence propagation neural network, BCPNN）以及多项目伽马泊松收缩模型（multi-item gamma Poisson shrinker, MGPS）进行失衡分析。此外，本研究还对瑞普替尼相关不良事件的发病时间（time-to-onset, TTO）进行了描述性分析。 研究结果：从FAERS数据库中共检索到3513份以瑞普替尼为主要可疑药物（primary suspect, PS）的ICSRs。在首选术语（preferred term, PT）层面，本研究共检测出116个阳性不良事件信号。常见不良事件包括脱发、便秘、肌肉痉挛、皮肤干燥、食欲下降。值得注意的是，本研究还观察到胸膜肿块、血镁异常、血钾异常、肝脏病变以及肝脓肿等未被报道的不良事件。瑞普替尼相关不良事件的中位发病时间为102天（四分位距29~254天），大多数不良事件发生在治疗首月内。 研究结论：本研究明确了瑞普替尼已知的相关不良事件，并发现了新的未被报道的不良事件，为其真实世界安全性提供了初步见解。该研究结果对于临床监测及瑞普替尼的安全用药具有重要参考价值。