Etanercept

Compound Name:EtanerceptMolecular Target:TNF? and TNF?Molecular Structure:TNFR-IgG1 Fc fusion proteinLicensed Indication:Rheumatoid Arthritis; Juvenile Idiopathic Arthritis; psoriatic arthritis; ankylosing spondylitis; plaque psoriasisManufacturer and/or Distributor:Amgen; WyethInitial FDA Approval1998SummaryEtanercept (Enbrel) is a dimeric, recombinant fusion protein consisting of the extracellular ligand-binding domain of the 75-kilodalton human (p75) tumor necrosis factor receptor (TNFR2) linked to the Fc portion of human IgG1. Etanercept specifically binds to TNFα and TNFb, both in the soluble and membrane forms, preventing interaction with cell surface TNF receptors and thereby reducing TNF activity. TNF is a pro-inflammatory cytokine produced by macrophages and lymphocytes and is one of the critical cytokines that mediate joint damage and destruction, as well as effects on other organs and body systems. TNF antagonists were the first of the biological disease-modifying anti-rheumatic drugs (DMARDS) to be approved for the treatment of RA. Etanercept is effective in reducing the signs and symptoms of RA, as well as slowing or halting radiographic damage. Etanercept is administered subcutaneously once or twice a week. It has an onset of action in 1 to 4 weeks. Additional improvements can be seen over 3-6 months. It was first licensed for use in rheumatoid arthritis in 1998. Etanercept is also approved for the treatment of psoriatic arthritis, polyarticular juvenile idiopathic arthritis, ankylosing spondylitis, and psoriasis. In October 2015, the FDA has accepted the Sandoz’s biosimilar to Enbrel. As with all TNF antagonists, a major concern is the increased risk of infection, particularly tuberculosis, invasive fungal infections, opportunistic pathogens, and bacterial sepsis. All patients should be screened for latent tuberculosis before beginning etanercept and during therapy. In September 2011, the FDA updated the Boxed Warnings for the entire class of TNF blockers to specifically include the risk of infection from Legionella and Listeria. Live vaccines should not be given to patients being treated with infliximab. Lymphoma and other malignancies are also potentially serious sides effects, although defining the magnitude of the risk has been difficult. Other important concerns are demyelinating disease, congestive heart failure, blood dyscrasias, reactivation of hepatitis B, lupus, autoimmune hepatitis, and allergic reactions, including anaphylaxis.References

Package insert: http://pi.amgen.com/united_states/enbrel/derm/enbrel_pi.pdf



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http://www.ncbi.nlm.nih.gov/pubmed/10075615


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http://www.ncbi.nlm.nih.gov/pubmed/25289064

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