Febuxostat Linked to Higher Hepatotoxicity Risk Than Benzbromarone in Gout Patients
A comparative cohort study published in Arthritis Care & Research has found that febuxostat is associated with a substantially higher risk of hepatotoxicity compared to benzbromarone in patients with gout. The findings, derived from real-world clinical data and rigorous propensity score matching, suggest that clinicians should exercise caution when prescribing febuxostat, particularly in patients with elevated liver enzymes at baseline.
“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,” the authors wrote.
Using electronic health records, the researchers identified new users of febuxostat or benzbromarone who had at least 3 liver function tests within the year following treatment initiation. A total of 2338 patients met eligibility criteria. Propensity score matching (PSM) was performed 1:1 between the 2 treatment groups, adjusting for age, sex, and pretreatment ALT and AST levels. Kaplan-Meier and Cox regression analyses were employed to assess time to hepatotoxicity, defined as ALT or AST levels exceeding 3 times the upper limit of normal.
After matching, 488 patients from each treatment group were analyzed over a mean follow-up of 1.2 years. Hepatotoxicity incidence was 39.6 per 1000 person-years in the febuxostat group, compared to 16.8 per 1000 person-years in the benzbromarone group. Febuxostat use was associated with a significantly higher risk of liver function abnormalities (adjusted hazard ratio [HR] 2.75; 95% CI: 1.28–5.91). The association was especially pronounced in individuals who had elevated liver enzymes prior to treatment initiation.
“Febuxostat use is associated with a significantly greater risk of mild-to-moderate perturbation of liver function compared to benzbromarone in patients with gout,” the study concluded.
Reference
Sun W, Cui L, Terkeltaub R, Chen Y, Li X, Cheng X, Liu T, Dalbeth N, Li C. Risk of hepatotoxicity in patients with gout treated with febuxostat or benzbromarone: a propensity score-matched cohort study. Arthritis Care Res (Hoboken). 2025;77(9):1149-1156. doi: 10.1002/acr.25547.
