Hepatotoxicity due to tocilizumab and anakinra in rheumatoid arthritis: two case reports

Mahmud Mahamid^1,3, Kalman Paz³, Mader Reuven⁴ Rifaat Safadi^1,2
1Liver Unit, Holy Family Hospital, Nazareth, Israel; ²Hadassah Medical Center, ³Shaare Zedek Medical Center, Jerusalem, Israel

Abstract: Elevation of liver enzymes in patients with rheumatoid arthritis treated with the biological agents, tocilizumab and anakinra, is now well documented. However, histological characterization of these effects and outcomes has not been defined. Here we report toxic liver effects in two women with rheumatoid arthritis, refractory to all nonbiological therapies, following treatment with anakinra and tocilizumab. Liver biopsy in both cases showed focal necrosis of hepatocytes as a hallmark of drug toxicity, along with steatosis and early fibrosis. In addition, the patient treated with anakinra demonstrated inflammatory changes. Tocilizumab was continued with no further deterioration in liver function. Withdrawal of anakinra led to rapid normalization of liver function. The biological agents, tocilizumab and anakinra, may result in significant histological hepatic changes, including necrosis, but despite this, the outcome appears to be good.

Keywords: tocilizumab, anakinra, interleukin receptors, lymphocytes, liver injury, rheumatoid arthritis