Febuxostat use in gout patients may increase risk of hepatotoxicity: Study

A new study published in the journal of Arthritis Care & Research showed that in individuals with gout, usage of Febuxostat is linked to a noticeably higher risk of mild-to-moderate liver function disruption than using benzbromarone.

Despite the effectiveness and widespread availability of urate-lowering treatment (ULT), gout is still not well treated, in part due to worries about adverse medication reactions. Although it can result in a rare hypersensitivity syndrome that is more prevalent in those of Southeast Asian heritage, allopurinol is advised as the recommended first-line treatment. Allopurinol and Febuxostat are equally effective for ULT.

Metabolic dysfunction–associated steatohepatitis (MASH) affects around 25% of gout sufferers, and it may raise the risk of drug-induced liver damage. Therefore, it has been suggested that serum liver function tests (LFTs) be monitored during ULT. This study assessed the hepatotoxicity risk of benzbromarone and febuxostat usage in gout patients.

An electronic medical record database was used to identify new users of benzbromarone or febuxostat who had their liver function monitored at least three times within a year after starting the study medications. The two groups were matched 1:1 for age, sex, and pretreatment levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in order to perform propensity score matching (PSM). The chance of hepatotoxicity (defined as ALT or AST > 3× upper limit of normal) was estimated using Kaplan-Meier analysis. Based on comorbidities, body mass index, and age, subgroup analysis was carried out.

A total of 2,338 gout patients in all were qualified. For AST or ALT abnormalities, 37% of patients had Common Terminology Criteria for Adverse Events version 5 grades 1–3. Following PSM, 488 users of febuxostat were paired, and 488 of them received benzbromarone throughout a mean follow-up of 1.20 years. For users of benzbromarone and febuxostat, the incidence of hepatotoxicity was 16.8 and 39.6 per 1,000 person-years, respectively.

When compared to benzbromarone, the use of Febuxostat was linked to a noticeably higher risk of hepatotoxicity, particularly in individuals whose baseline transaminases were increased. The results did not vary based on the predefined subgroups. Overall, gout patients who begin taking febuxostat as opposed to benzbromarone are much more likely to experience bouts of hepatotoxicity, which are characterized as ALT or AST >3 times ULN.

Referene:

Sun, W., Cui, L., Terkeltaub, R., Chen, Y., Li, X., Cheng, X., Liu, T., Dalbeth, N., & Li, C. (2025). Risk of hepatotoxicity in patients with gout treated with febuxostat or benzbromarone: A propensity score-matched cohort study. Arthritis Care & Research. https://doi.org/10.1002/acr.25547