Risk of Hepatotoxicity in Patients With Gout Treated With Febuxostat or Benzbromarone: A Propensity Score-Matched Cohort Study.

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.