| Description | Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary mammalian cell lineand is the first biotechnology-derived drug to be introduced for the reduction of the signs and symptoms ofmoderately to severely active rheumatoid arthritis in patients who have not adequately responded to one or more ofthe synthetic DMARDs. It is a dimeric soluble form of the p75 TNFR capable of binding to two TNF molecules in thecirculation. It consists of the extracellular ligand binding portion of the 75-kDa human TNFR fused to the Fc portionof human IgG1.
The Fc component of etanercept contains the CH2 domain, the CH3 domain, and thehinge region, but not the CH1 domain of IgG1. It consists of 934 amino acids and has an apparent molecular weightof approximately 150 kDa. Two TNFRs have been identified, a 75-kDa protein and a 55-kDa protein, that occur asmonomeric molecules on cell surfaces and soluble forms in the blood. The biological activity of TNF requires itsbinding to either of the two cell surface TNFRs. Etanercept can bind specifically to two molecules of TNFα in thecirculation, preventing its interaction with cell surface TNFRs. |
| History | Etanercept (brand name Enbrel ) was discovered by Immunex in September 1989. The fusion protein was developed by Bruce A. Beutler, an academic researcher then at the University of Texas Southwestern Medical Center at Dallas, and colleagues, who patented it and licensed the rights in 1995 to Immunex. Another patent on such fusion protein technology from Brian Seed at Massachusetts General Hospital was licensed to Immmunex in 1997. Etanercept was approved for use in the United States in November 1998. Etanercept was approved for use in the European Union in February 2000. |
| Uses | To decrease signs and symptoms of rheumatoid arthritis.
Etanercept (Enbrel) is a soluble TNF receptor fusion protein. It is FDA approved for moderate to severe psoriasis at a dose of 50 mg twice weekly by subcutaneous injection for the initial 12 weeks, followed by a stepdown to 50 mg weekly for maintenance. The most common side effect is injection site reactions. Rare cases of serious infection, demyelinating disease, and congestive heart failure have been reported by postmarketing surveillance. |
| Indications | Etanercept (Enbrel) is a recombinant fusion protein designedto block the action of TNF-α.The drug is composed of the extracellular ligand-bindingportion of the 75-kilodalton human TNF receptorlinked to the Fc portion of human IgG1. TNF-α is a cytokinethought to play a major role in the pathogenesisof a number of inflammatory skin diseases, includingpsoriasis. Etanercept binds soluble TNF-α, preventing itfrom binding to and activating receptors for TNF thatare present on cell membranes. |
| Indications | Etanercept is a recombinant fusion protein produced inChinese hamster ovary cells. It consists of the intracellularligand-binding portion of the human p75 TNF receptorlinked to the Fc portion of human immunoglobulin(Ig) G1.Two p75 molecules are attached to each Fcmolecule. Etanercept binds to soluble TNF-αand TNF-βand forms inactive complexes, effectively loweringcirculating levels of these cytokines. It is administeredsubcutaneously, generally twice weekly. |
| Brand name | Enbrel (Immunex);Tanercept yhu. |
| Pharmacology | Etanercept (Enbrel) is a soluble TNF receptor fusion protein. It is FDAapproved for moderate to severe psoriasis at a dose of 50 mg twice weeklyby subcutaneous injection for the initial 12 weeks, followed by a stepdownto 50 mg weekly for maintenance. |
| Clinical Use | Etanercept is approved in the United States for thetreatment of psoriatic arthritis and rheumatoid arthritis.Although etanercept has not been specifically approvedfor the treatment of the cutaneous manifestations ofpsoriasis, it significantly improves the skin lesions of patientswith moderate to severe cutaneous psoriasis whohave used it for psoriatic joint disease. |
| Side effects | The most common adverse reaction to etanercept ismild to moderate erythema, pain, or pruritus at the injectionsite (37%). Headaches and abdominal pain canalso occur. New positive autoantibodies, such as antinuclearantibodies (ANA), anti-dsDNA antibodies, andanticardiolipin antibodies, can develop in patientstreated with etanercept. Although there is so far no associationbetween this and the development of autoimmunediseases or malignancies, long-term studies haveyet to be done. Rare cases of pancytopenia may be associatedwith this drug. Although clinical trials showedno increased risk of infection with etanercept treatment,postmarketing reports of serious infections, sepsis,and associated fatalities exist. |
| Drug interactions | Potentially hazardous interactions with other drugs Anakinra and abatacept: avoid concomitant use. Live vaccines: avoid concomitant use. |
| Metabolism | Since etanercept is a fusion glycoprotein, consisting entirely of human protein components, it is expected to undergo proteolysis |
| Precautions | Etanercept therapy should not be initiated in patientswith active infection. If an infection develops in a persontaking etanercept, he or she should be closely monitored.If a serious infection or sepsis occurs, the drugshould be discontinued. Etanercept should be usedwith caution in individuals who have conditions predisposingthem to serious infection (e.g., uncontrolleddiabetes, hematological abnormalities). Data on druginteractions are limited. Live virus vaccines are contraindicatedbecause of the potential for secondarytransmission of the infection by the vaccine. Myelosuppressiveantirheumatic agents have been associatedwith pancytopenia in some patients treated with etanercept. |
