Article: Etanercept

Etanercept
Systematic (IUPAC) name
Unable to be assigned
Identifiers
CAS number	185243-69-0
ATC code	L04AA11
PubChem	N/A
DrugBank	BTD00052
Chemical data
Formula	C2224H3475N621O698S36
Mol. weight	51234.9 g/mol
Pharmacokinetic data
Bioavailability	58–76% (SC)
Metabolism	Reticuloendothelial system (speculative)
Half life	70–132 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	B2 (Au), B (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Subcutaneous

Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNFα) receptor. It is is a small protein, with a molecular weight of 75 kDa (p75), that binds to TNFα and decreases its role in inflammatory diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, and ankylosing spondylitis. It is co-marketed by Amgen and Wyeth under the trade name Enbrel.

Development

Etanercept was developed by researchers at biotechnology company Immunex, which was subsequently purchased by Amgen. It was released in 1999, soon after the release of infliximab (Remicade) – the first chimeric monoclonal antibody against TNFα to be marketed for clinical use.

Mode of action

Tumor necrosis factor-alpha (TNFα) is a cytokine produced by monocytes and macrophages, two types of white blood cells. It mediates the immune response by increasing the transport of white blood cells to sites of inflammation. Inhibition of its action by etanercept reduces the inflammatory response which is especially useful for treating autoimmune diseases.

There are two types of TNF receptors: those found embedded in white blood cells that respond to TNF by releasing other cytokines, and soluble TNF receptors which are used to deactivate TNF and blunt the immune response. Etanercept mimics the inhibitory effects of naturally occurring soluble TNF receptors.

Structure

Etanercept is made from the combination of two naturally occurring soluble human 75-kilodalton TNF receptors linked to an Fc portion of an IgG1. The effect is an artificially engineered antibody.

Administration

Enbrel is marketed as a powder which must be reconstituted with a diluent and then injected subcutaneously, typically by the patient at home. It cannot be administered orally, because the digestive system would destroy the drug. Also available now in a 50 mL pre-dissolved syringe.

Safety

According to the product labeling of infliximab, etanercept, and adalimumab, these drugs are in the class of immunosuppressants. After a number of studies and reports of adverse reactions in patients receiving anti-TNF alpha therapy (including serious and sometimes fatal blood disorders, infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, and rare reports of demyelinating central nervous system disorders), the U.S. Food and Drug Administration issued a warning to doctors appearing in the respective product labeling of these drugs instructing them to screen and monitor potential patients more carefully.

Similar agents

• Infliximab
• Adalimumab