Risk of hepatotoxicity in patients with gout treated with febuxostat or benzbromarone: a propensity score-matched cohort study.

Abstract

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 to match for age, sex, and pre-treatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Kaplan-Meier analysis was used to estimate the probability of hepatotoxicity (defined as ALT or AST >3x upper limit of normal). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression. Subgroup analysis was performed based on age, body mass index, and comorbidities.

Results: 2,338 patients with gout were eligible. A total of 37% experienced Common Terminology Criteria for Adverse Events (CTCAE) v5 grade 1-3 AST/ALT abnormality. After PSM, 488 febuxostat users were matched with 488 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 pre-specified 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.