Tumor necrosis factor alpha (TNFα) is a bioactive cytokine that is an important component of inflammatory and pain pathways. Inhibition of TNFα 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 approved for use in the United States: a mouse-human chimeric monoclonal antibody to TNFα (infliximab), two human monoclonal antibodies to TNFα (adalimumab and golimumab), a humanized Fab fragment of anti-TNFα linked to polyethylene glycol (certolizumab pegol), and a soluble recombinant fusion protein of the TNFα cellular receptor and an IgG fragment (etanercept) which on binding to tNF blocks its activity and leads to its degradation. These TNFα 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 other inflammatory arthridities (psoriatic arthritis, juvenile idiopathic arthritis, and anklylosing spondylitis) and are considered “disease modifying anti-rheumatic drugs” (DMARDs), having been shown to decrease pain, improve function, and ameliorate progressive joint damage. The monoclonal antibodies to TNFα have also been shown to be effective in inflammatory bowel disease (Crohn’s disease and ulcerative colitis). In contrast, etanercept, a recombinant soluble TNFα receptor, is not effective in inflammatory bowel disease and is approved only as therapy of the inflammatory arthridities. The five TNFα antagonists appear to have similar efficacy against the rheumatic diseases but vary by indications, route of administration (intravenous vs subcutaneous) and dose regimens (every 1, 2, 4 or 8 weeks) (Table). The frequency and types of adverse side effects also vary. Generic versions (biosimilars) are available for some but not all of the TNFα antagonists and they are usually only slightly less expensive than the standard branded product.
Among the TNFα antagonists, infliximab has been most frequently linked to liver injury, including asymptomatic serum aminotransferase elevations, induction of clinically apparent autoimmune hepatitis, fulminant hepatitis, cholestatic hepatitis, vanishing bile duct syndrome, and reactivation of hepatitis B. However, the other anti-TNFα monoclonal antibodies have been less extensively studied, and liver injury of TNFα antagonists is probably class specific. For these reasons, all five of these agents should be considered potentially hepatotoxic, etanercept perhaps less so and infliximab more so than the others.
Drug Class: Antirheumatic Agents; Gastrointestinal Agents; Psoriasis Agents