Three-year outcomes of tumor necrosis factor alpha inhibitor therapy in rheumatoid arthritis patients with elevated liver enzymes

BACKGROUND Elevated liver enzymes in rheumatoid arthritis (RA) are often attributed to multiple factors including disease activity and treatment-related adverse effects. Tumor necrosis factor inhibitors (TNFi) have shown mixed effects on liver function, with varying safety profiles among agents. AIM To evaluate the hepatic safety of TNFi therapy—etanercept and adalimumab—in RA patients with elevated liver enzymes. METHODS A retrospective chart review was conducted for RA patients with elevated liver enzymes receiving TNFi at a single center between January 1, 2019, and September 30, 2024. Out of the patients screened, 9 met the inclusion criteria. Trends in liver enzymes, fibrosis-4 (FIB-4) score, and changes in the Child-Pugh class were analyzed at 1-year and 3-year follow-up periods. RESULTS Among 9 patients (4 on adalimumab, 5 on etanercept), the median age was 56 years [interquartile range (IQR): 49.5–64.5 years], 77.8% were female, and the median body mass index was 36.99 kg/m² (IQR: 30.95–43.43 kg/m²). Median baseline FIB-4 was 1.25 (IQR: 1.02–1.65), with no cirrhosis observed at baseline. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels declined consistently, with significant reductions from baseline to 3 years (P = 0.003). FIB-4 scores also significantly decreased (P = 0.003), while albumin, bilirubin, and Child-Pugh class remained stable at the 3-year follow-up. At 3 years, 66.7% achieved RA remission (P = 0.03). CONCLUSION TNFi therapy (adalimumab or etanercept) was associated with significant improvement in liver enzymes and FIB-4 without hepatic decompensation, supporting its safety in our cohort of RA patients with liver involvement. Larger prospective studies are warranted to further validate these findings.