Etanercept

Description

Etanercept is produced by recombinant DNA technology in a Chinese hamster ovary mammalian cell line and is the first biotechnology-derived drug to be introduced for the reduction of the signs and symptoms of moderately to severely active rheumatoid arthritis in patients who have not adequately responded to one or more of the synthetic DMARDs. It is a dimeric soluble form of the p75 TNFR capable of binding to two TNF molecules in the circulation. It consists of the extracellular ligand binding portion of the 75-kDa human TNFR fused to the Fc portion of human IgG1.

The Fc component of etanercept contains the CH2 domain, the CH3 domain, and the hinge region, but not the CH1 domain of IgG1. It consists of 934 amino acids and has an apparent molecular weight of approximately 150 kDa. Two TNFRs have been identified, a 75-kDa protein and a 55-kDa protein, that occur as monomeric molecules on cell surfaces and soluble forms in the blood. The biological activity of TNF requires its binding to either of the two cell surface TNFRs. Etanercept can bind specifically to two molecules of TNFα in the circulation, preventing its interaction with cell surface TNFRs.

The Uses of Etanercept

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 designed to block the action of TNF-α. The drug is composed of the extracellular ligand-binding portion of the 75-kilodalton human TNF receptor linked to the Fc portion of human IgG1. TNF-α is a cytokine thought to play a major role in the pathogenesis of a number of inflammatory skin diseases, including psoriasis. Etanercept binds soluble TNF-α, preventing it from binding to and activating receptors for TNF that are present on cell membranes.

Indications

Etanercept is a recombinant fusion protein produced in Chinese hamster ovary cells. It consists of the intracellular ligand-binding portion of the human p75 TNF receptor linked to the Fc portion of human immunoglobulin (Ig) G1.Two p75 molecules are attached to each Fc molecule. Etanercept binds to soluble TNF-αand TNF-β and forms inactive complexes, effectively lowering circulating levels of these cytokines. It is administered subcutaneously, generally twice weekly.

brand name

Enbrel (Immunex);Tanercept yhu.

Pharmacology

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.

Clinical Use

Etanercept is approved in the United States for the treatment of psoriatic arthritis and rheumatoid arthritis. Although etanercept has not been specifically approved for the treatment of the cutaneous manifestations of psoriasis, it significantly improves the skin lesions of patients with moderate to severe cutaneous psoriasis who have used it for psoriatic joint disease.

Side Effects

The most common adverse reaction to etanercept is mild to moderate erythema, pain, or pruritus at the injection site (37%). Headaches and abdominal pain can also occur. New positive autoantibodies, such as antinuclear antibodies (ANA), anti-dsDNA antibodies, and anticardiolipin antibodies, can develop in patients treated with etanercept. Although there is so far no association between this and the development of autoimmune diseases or malignancies, long-term studies have yet to be done. Rare cases of pancytopenia may be associated with this drug. Although clinical trials showed no 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.