Tumor necrosis factor (TNF) alpha is a bioactive cytokine that is an important component of the inflammatory and pain pathways. Inhibition of TNF can decrease the inflammatory response, and this approach has been used in therapy of autoimmune conditions, most effectively in inflammatory bowel disease (IBD), rheumatoid arthritis, juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis), psoriasis, psoriatic arthritis and ankylosing spondylitis. Five anti-TNF antagonists have been developed and introduced into clinical medicine: a mouse-human chimeric monoclonal antibody to TNF (infliximab), two human monoclonal antibodies to TNF (adalimumab and golimumab), a humanized Fab fragment of anti-TNF linked to polyethylene glycol (certolizumab), and a soluble recombinant form of the TNF cellular receptor (etanercept) which, on binding, blocks the activity of TNF. These TNF antagonists have potent activity in several autoimmune diseases marked by excessive production of this proinflammatory cytokine. All five of these agents are approved for use in rheumatoid arthritis and are considered “disease modifying anti-rheumatic drugs” (DMARDs), having been shown to decrease pain, improve function, and ameliorate progressive joint damage in rheumatoid arthritis. The monoclonal antibodies to TNF have also been shown to be effective in psoriatic arthritis, ankylosing spondylitis and inflammatory bowel disease. The five agents rarely cause serum aminotransferase elevations, but have been linked to rare instances of clinically apparent, acute liver injury which often resembles autoimmune hepatitis and can be severe or require corticosteroid therapy. TNF antagonists are also immunosuppressive and can lead to reactivation of latent infections such as tuberculosis and hepatitis B. Severe and even fatal instances of reactivation of hepatitis B have been linked to several anti-TNF agents, and routine screening for HBsAg before starting therapy with these agents is recommended. Patients with HBsAg should receive prophylaxis with an oral antiviral agent during therapy with one of the TNF antagonists.
Among the TNF antagonists, infliximab has been most frequently and etanercept least frequently linked to liver injury, including asymptomatic serum aminotransferase elevations, induction of clinically apparent autoimmune hepatitis, and reactivation of hepatitis B. However, infliximab has been most extensively used and studied than the other anti-TNF monoclonal antibodies, and liver injury due to these agents is probably class specific. For these reasons, all five of these agents should be considered potentially hepatotoxic, etanercept perhaps less so that the others.
Drug Class: Antirheumatic Agents; Gastrointestinal Agents; Psoriasis Agents