Application of Tocilizumab in Drug-Induced Liver Injury: Pharmacovigilance Study Using the FAERS Database and the Drug-Gene Interaction Network Analysis

Objective: This study aimed to investigate the characteristics of hepatic injury induced by tocilizumab through the FDA Adverse Event Reporting System (FAERS) database, which highlights the need for close monitoring of liver function during clinical use. Additionally potential toxicological mechanisms are explored through drug-gene interaction network analysis. Methods: Liver injury reports associated with tocilizumab were collected from the FDA Adverse Event Reporting System (FAERS) database (from June 2014 to June 2024) using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods. Subsequently, pathway enrichment and the drug-gene interaction network analyses were conducted to identify the potential molecular mechanisms underlying tocilizumab-induced liver injury. Results: Within the FAERS database, 244,736 adverse event reports associated with tocilizumab were analyzed, of which 2,658 cases (1.09%) were identified as drug-induced hepatic injury. Notably, the disproportionality analysis revealed significantly elevated risks for tocilizumab compared to other medications, with a reporting odds ratio (ROR) of 3.12 (95% CI: 2.98-3.27) and a proportional reporting ratio (PRR) of 3.09 (χ²= 1,024.7, p <0.001). Clinically, hepatic injury predominantly manifested as elevated liver enzymes (68.2%), liver dysfunction (21.5%), and abnormal hepatic function tests (10.3%). Strikingly, a pronounced sex disparity was observed, with female patients constituting 80.6% of cases (6.8-fold higher incidence than males). Furthermore, demographic stratification demonstrated peak susceptibility in individuals aged 19-45 years (39.1% of cases) and those weighing 61-85 kg (41.9%). Temporally, 72.4% of hepatic injury events occurred within the first treatment month. Mechanistically, integrated proteomic analysis identified several key genes implicated in hepatic injury pathogenesis (PTGS2, ESR1, MMP9), with KEGG pathway enrichment highlighting multiple pathways associated with inflammatory responses. Conclusion: The clinical use of tocilizumab in China should be approached with caution due to the risk of hepatotoxicity, and regular monitoring of liver function every 2 to 4 weeks is recommended.