Sun Wenyan, Cui Lingling, Terkeltaub Robert, Chen Ying, Li Xinde, Cheng Xiaoyu, Liu Tian, Dalbeth Nicola, Li Changgui
The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
University of California, San Diego.
Arthritis Care Res (Hoboken). 2025 Sep;77(9):1149-1156. doi: 10.1002/acr.25547. Epub 2025 May 8.
The objective of this study was to evaluate and compare the risk of hepatotoxicity associated with the use of febuxostat and benzbromarone in patients with gout.
New users of febuxostat or benzbromarone with monitoring of liver function at least three times in a year after initiation of the study drugs were identified from an electronic medical record database. Propensity score matching (PSM) was performed between the two groups 1:1 matched for age, sex, and pretreatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Kaplan-Meier analysis was used to estimate the probability of hepatotoxicity (defined as ALT or AST > 3× upper limit of normal). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. Subgroup analysis was performed based on age, body mass index, and comorbidities.
A total of 2,338 patients with gout were eligible. A total of 37% of patients experienced Common Terminology Criteria for Adverse Events version 5 grades 1 to 3 for AST or ALT abnormality. After PSM, 488 febuxostat users were matched, with 488 participants receiving benzbromarone with a mean follow-up of 1.20 years. The incidence of hepatotoxicity was 39.6 and 16.8 per 1,000 person-years for febuxostat users and benzbromarone users, respectively. Febuxostat use was associated with a significantly greater risk of hepatotoxicity than benzbromarone (adjusted HR 2.75, 95% CI 1.28-5.91), especially in patients with elevated transaminases at baseline. Findings did not differ according to prespecified subgroups.
Febuxostat use is associated with a significantly greater risk of mild-to-moderate perturbation of liver function compared to benzbromarone in patients with gout.
本研究旨在评估和比较痛风患者使用非布司他和苯溴马隆后肝毒性的风险。
从电子病历数据库中识别出在开始使用研究药物后每年至少监测三次肝功能的非布司他或苯溴马隆新使用者。对两组进行倾向评分匹配（PSM），按照年龄、性别以及治疗前丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）进行1:1匹配。采用Kaplan-Meier分析来估计肝毒性（定义为ALT或AST>正常上限的3倍）的概率。使用Cox回归计算风险比（HRs）和95%置信区间（CIs）。根据年龄、体重指数和合并症进行亚组分析。
共有2338例痛风患者符合条件。共有37%的患者出现了不良事件通用术语标准第5版中1至3级的AST或ALT异常。PSM后，匹配了488名非布司他使用者和488名接受苯溴马隆治疗的参与者，平均随访1.20年。非布司他使用者和苯溴马隆使用者的肝毒性发生率分别为每1000人年39.6例和16.8例。与苯溴马隆相比，使用非布司他与显著更高的肝毒性风险相关（校正HR 2.75，95% CI 1.28 - 5.91），尤其是在基线转氨酶升高的患者中。根据预先设定的亚组分析结果无差异。
与苯溴马隆相比，痛风患者使用非布司他与轻至中度肝功能损害的显著更高风险相关。
