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.