Table1_A real-world pharmacovigilance analysis of FDA adverse event reporting system database for upadacitinib.DOCX

Objective: To mine the adverse drug event (ADE) signals of upadacitinib based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to provide a reference for the safe clinical use of the drug.
Methods: The ADE data for upadacitinib from Q1 2004 to Q1 2023 in the FAERS database were retrieved, and data mining was performed using the reporting odds ratio and proportional reporting ratio.
Results: A total of 21,213 ADE reports for the primary suspect drug upadacitinib were obtained, involving 444 ADEs. Patients aged ≥60 years (21.48%) and female (70.11%) patients were at a higher risk of ADEs with upadacitinib. After data cleaning, 182 ADE signals from 19 system organ classes (SOCs) were obtained. Six of these SOCs that occurred more frequently and were not mentioned in the drug labeling information included renal and urinary system (1.09%), reproductive and breast diseases (1.14%), ear and labyrinth disorders (0.57%), psychiatric disease (0.57%), blood and lymphatic system disorders (0.57%), and endocrine disorders (0.57%). The top ten most frequent ADE signals reported for upadacitinib were mainly related to: infections and infestations (7), investigations (2), and skin and subcutaneous tissue disorders (1). The top 10 ADEs in signal intensity ranking were lip neoplasm, ureteral neoplasm, eczema herpeticum, vulvar dysplasia, mediastinum neoplasm, eosinopenia, herpes zoster cutaneous disseminated, eye ulcer, acne cystic, and Moraxella infection. The top 10 high-frequency events leading to serious adverse events were urinary tract infection (2.74%), herpes zoster (1.63%), diverticulitis (1.19%), bronchitis (0.68%), nasopharyngitis (0.68%), localised infection (0.66%), nephrolithiasis (0.66%), pulmonary thrombosis (0.66%), blood cholesterol increased (0.55%), and Pneumocystis jirovecii pneumonia (0.53%).
Conclusion: Clinicians should be vigilant to upadacitinib-induced events in systems not covered in the drug labeling information and to new and highly signaled ADEs to ensure the safe and effective use of upadacitinib.

研究目标：本研究旨在基于美国食品药品监督管理局（Food and Drug Administration, FDA）不良事件报告系统（Adverse Event Reporting System, FAERS）数据库，挖掘乌帕替尼（upadacitinib）的药品不良事件（adverse drug event, ADE）信号，为该药的临床安全用药提供参考。
研究方法：检索FAERS数据库中2004年第一季度至2023年第一季度的乌帕替尼相关ADE数据，并采用报告比值比（reporting odds ratio, ROR）与比例报告比值法（proportional reporting ratio, PRR）开展数据挖掘。
研究结果：本研究共获取以乌帕替尼为主要可疑药物的ADE报告21213份，涉及444例不良事件。其中，年龄≥60岁的患者（21.48%）与女性患者（70.11%）发生乌帕替尼相关ADE的风险更高。经数据清洗后，共从19个系统器官分类（system organ class, SOC）中获取182个ADE信号。其中6个发生频次较高且未在药品说明书中提及的系统器官分类分别为：泌尿与泌尿系统（1.09%）、生殖系统与乳腺疾病（1.14%）、耳及迷路疾病（0.57%）、精神疾病（0.57%）、血液与淋巴系统疾病（0.57%）以及内分泌系统疾病（0.57%）。乌帕替尼上报频次最高的前10位ADE信号主要涉及感染与侵袭性疾病（7项）、检验检查（2项）以及皮肤与皮下组织疾病（1项）。按信号强度排序的前10位ADE分别为：唇部肿瘤、输尿管肿瘤、疱疹性湿疹、外阴发育异常、纵隔肿瘤、嗜酸性粒细胞减少症、播散性皮肤带状疱疹、眼部溃疡、囊性痤疮以及莫拉菌感染。导致严重不良事件的前10位高频事件分别为：尿路感染（2.74%）、带状疱疹（1.63%）、憩室炎（1.19%）、支气管炎（0.68%）、鼻咽炎（0.68%）、局限性感染（0.66%）、肾结石（0.66%）、肺血栓形成（0.66%）、血胆固醇升高（0.55%）以及耶氏肺孢子菌肺炎（0.53%）。
研究结论：临床医师应警惕乌帕替尼引发的药品说明书未覆盖系统的不良事件，以及信号强度较高的新型ADE，以保障乌帕替尼的安全有效使用。