Objective: 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.
Methods: 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.
Results: 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.
Conclusion: Febuxostat use is associated with a significantly greater risk of mild-to-moderate perturbation of liver function compared to benzbromarone in patients with gout.
© 2025 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.