Higher Hepatotoxicity Risk With Febuxostat Over Benzbromarone in People With Gout

New research has found that febuxostat use in patients with gout was associated with a significantly greater risk of mild to moderate perturbation of liver function compared to benzbromarone.1

Lead investigator Wenyan Sun, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China, and colleagues identified new users of febuxostat or benzbromarone from an electronic medical record database that had liver function monitored at least 3 times in a year after initiating the study drugs. They performed propensity score matching (PSM) between the 2 groups 1:1 to match for age, sex, and pre-treatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST). They also used Kaplan-Meier analysis to estimate the probability of hepatotoxicity (defined as ALT or AST >3x upper limit of normal) and calculated hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. The investigators further performed subgroup analysis based on age, body mass index, and comorbidities.

The analysis included 2,338 participants with gout. Of these participants, 37% experienced grade 1-3 AST/ALT abnormality adverse events (AE). After PSM, 488 participants using febuxostat were matched with 488 receiving benzbromarone with a mean follow-up of 1.20 years. Sun and colleagues found that in this population, participating receiving febuxostat had an incidence of hepatotoxicity of 39.6 per 1,000 person-years and participants receiving benzbromarone had an incidence of hepatotoxicity of 16.8 per 1,000 person-years. Accordingly, febuxostat use was associated with a significantly greater risk of hepatotoxicity than benzbromarone (adjusted HR, 2.75 [95% CI, 1.28-5.91]). Participants with elevated transaminases at baseline had higher risk of hepatotoxicity. Subgroup analyses did not reveal any significant findings.

Other recent research into renal injury risk in people with gout found that monocyte-to-HDL-C ratio (MHR) was found to be correlated with gout risk and renal dysfunction severity. Lead investigator Liangyu Mi, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China, and colleagues used data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2016 to conduct a cross-sectional analysis to assess the correlation between MHR levels and gout. They used multiple logistic regression, subgroup analyses, and exploration of nonlinear relationships to analyze data from 7247 participants, 373 with gout.2

The investigators found that MHR was significantly higher in gout patients (0.54; standard deviation [SD], 0.31) compared to non-gout patients (0.47; SD, 0.24). After adjusting for confounding factors, MHR was significantly associated with gout risk (odds ratio [OR], 1.6 [95%CI, 1.1–2.2]; P = .012). They also found that after adjustments, each unit increase in MHR significantly raised the risk of gout by approximately 0.6-fold.2

Furthermore, subgroup analyses revealed a positive correlation between MHR and gout risk in males, Mexican Americans(OR, 5.0 [95% CI, 1.5–17.4]; P = .011), and participants who were married (OR, 1.8 [95% CI, 1.2–2.8]; P = .008), had insufficient physical activity (OR, 1.6; P <.05), and diabetes(OR, 3.5; P <.05).2

Notably, MHR had a stronger positive association in patients who had gout with renal dysfunction (OR, 7.4 [95% CI, 2.2–25.3]; P = .001). Patients in the highest MHR quartile had a 1.7-fold higher prevalence of gout with renal dysfunction than the lowest quartile (OR, 2.7 [95% CI, 1.1-6.7]; P = .028).2

“The findings of this study indicate a substantial positive correlation between the MHR and gout, highlighting its potential as a useful biomarker for evaluating the risk and severity of the disease and its complications. Moreover, the study reveals that MHR is linked to the progression of renal impairment in individuals with gout. These results underscore the importance of considering MHR as a valuable indicator in the management and assessment of gout-related health issues,” Mi and colleagues concluded.2

REFERENCES

1. Sun W, Cui L, Terkeltaub R, et al. Risk of hepatotoxicity in patients with gout treated with febuxostat or benzbromarone: a propensity score-matched cohort study. Arth. Care Res. Published online April 7, 2025. doi: 10.1002/acr.25547

2. Mi L, He X, Gao J, Xu K. Monocyte-to-HDL cholesterol ratio (MHR) as a novel Indicator of gout risk. Sci Rep. 2025; 15 (12188). doi.org/10.1038/s41598-025-97373-w