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Etanercept (Enbrel) is a recombinant fusion protein designed to block the action of TNF-a (see Chapter 40). The drug is composed of the extracellular ligand-bind-ing portion of the 75-kilodalton human TNF receptor linked to the Fc portion of human IgGj. TNF-a 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-a, preventing it from binding to and activating receptors for TNF that are present on cell membranes.

Etanercept is administered by subcutaneous injection. The maximum serum concentration is reached after approximately 72 hours. The half-life is approximately 115 hours.

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.

Injection site reactions characterized by mild to moderate erythema, itching, burning, and/or pain occur in approximately one-third of patients but rarely necessitate drug discontinuation. The impact of etanercept on the host's response to new or chronic infections is not fully understood. Serious infections and sepsis, including fatalities, have been reported in patients treated with etanercept. Increased levels of autoantibodies, including antinuclear antibodies and anti-double-stranded DNA antibodies, have also been reported, but the clinical significance of this observation is unknown.

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