The pharmacological class of TNF alpha inhibitors includes etanercept (Enbrel) infliximab (Remicade) and adalimumab (HUMIRA), among others (see below). These drugs share mechanisms of action and therapeutic uses (rheumatologic diseases, bowel inflammatory disease and psoriasis). The first approved TNF alpha blocker was etanercept (Enbrel) in May 1998. Then came infliximab (Remicade) in November 1999, while adalimumab (HUMIRA) was approved in December 2002. TNF alpha, a key cytokine for the development of the inflammatory responseAn excerpt from the excellent “ Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy” by D. Golan , A.H. Tashjian , E. J. Armstrong and A. W Armstrong
Anti TNF agents molecular characteristicsEtanercept (Enbrel): Soluble TNF receptor fusion protein. As you can see in the image, etanercept molecule consists of 2 extracellular domains of human soluble TNF receptor p75 that binds to TNF and a Fc fragment of human IgG that serves as a stabilizer. Infliximab (Remicade): chimeric human-mouse anti-TNF alpha . This drug is 25% murinal (mouse) derived and 75% human. The binding epitope for TNF is of murine origin while the IgG fragment is of human origin. Adalimumab (HUMIRA- Human Monoclonal Antibody in Rheumatoid Arthritis-): fully human anti-tumor necrosis factor alpha monoclonal antibody produced by phage-display technology. i The TNF alpha inhibitors share therapeutic usesThis chart shows the latest (May 2009) information on the FDA approved uses of three selected TNF alpha blockers.
Source: FDA.gov Newer TNF alpha blockersCertolizumab pegol (Cimzia): pegylated humanized Fab’ fragment that binds tumor necrosis factor alpha. FDA approved it in April 2008 for the treatment of Crohn’s disease. Golimumab (Simponi). Approved in April 2009 for: moderate-to-severe rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis. TNF blockers adverse effects: risks of tuberculosis reactivation and invasive fungal infectionsTNF inhibitors have a number of known side effects, mainly related to their immunosuppressant activity. Since TNF is a important cytokine when fighting against tuberculosis, these drugs can reactivate a latent tuberculosis infection. The official FDA presentation below discusses adverse effects associated with TNF blockers: infections (tuberculosis, histoplasmosis and other invasive fungal infections) , congestive heart failure, neurologic events, malignancies and autoimmunity. Download PPT file This is a FDA patient safety alert video, warning about the risk of serious fungal infections in patients receiving TNF alpha inhibitors. Also, the UK’s National Institute for Health and Clinical Excellence (NICE) issued in February 2009 an update of the rheumatoid arthritis clinical guideline. |
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