Hepatic Safety of Febuxostat and Allopurinol in Gout Patients: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: This study aimed to conduct an updated systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the hepatic safety of febuxostat and allopurinol in gout patients. Subgroup analyses were conducted based on age, dosage, and treatment duration.

METHODS

This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published studies were reviewed in PubMed, The Cochrane Library, and Scopus. The Cochrane Risk of Bias (RoB) 2 tool was used to assess the quality of the included studies. Risk ratios (RR) were estimated using binary outcomes of fixed effect model and were reported with corresponding 95% confidence intervals (CI). This study is registered on PROSPERO with number CRD42024611074.

RESULTS

Out of 703 publications from the databases, a total of 15 studies met the inclusion criteria. The RR meta-analysis of the included studies was calculated using binary outcomes and a fixed effect model based on available hepatic safety events. We identified 5 RCTs with some concerns regarding the risk of bias, and 10 RCTs with a low risk of bias. Overall, hepatic safety outcomes were comparable between febuxostat and allopurinol, including across subgroups by age, dosage, and treatment duration. Febuxostat showed no significant difference in hepatic risk compared to allopurinol, with RRs of 1.03 (95% CI: 0.78-1.36) for overall liver function abnormalities, 1.03 (95% CI: 0.66-1.61) for investigator-defined liver abnormalities, and 1.21 (95% CI: 0.96-2.74) for hepatobiliary disorders.

CONCLUSION

This updated systematic review and meta-analysis found no difference in hepatic safety profiles between febuxostat and allopurinol in patients with gout across age categories, dosage levels, or treatment durations. Further research is warranted to address the limitations of sample sizes and the overall moderate quality of existing evidence.