Etanercept in arthritis

Abstract

Tumour necrosis factor-alpha (TNF-alpha) is one of the inflammatory cytokines. It is released by activated monocytes, macrophages and T lymphocytes and promotes inflammation. TNF-alpha binds to two receptors; one of these is the type 2 TNF receptor (p75). Etanercept is a soluble TNF-receptor fusion protein. It consists of two linked dimmers, each with a ligand-binding portion of the higher affinity type 2 TNF receptor (p75). This fusion protein binds to TNF-alpha and prevents it from interacting with its receptor. Etanercept is given by subcutaneous administration at a dose of 25 mg twice a week. This dosing reflects its half-life of about 4 days. Clinical trials show etanercept is effective and safe to use in rheumatoid arthritis (RA). It reduces disease activity and limits progressive joint damage in both early and late disease. It can be used as a monotherapy or in combination with methotrexate, and in this, the latter approach appears most effective. It is also effective in psoriatic arthritis and ankylosing spondylitis. Although the biologic appears safe, caution is needed to ensure it does not re-activate tuberculosis. It should not be used in patients with disseminated sclerosis, and there are concerns about a potential relationship to lymphoma. Its high cost means there will be continuing debate about the ideal position of this new biologic within the treatment pathway of RA. At present, it is recommended for use when methotrexate and another disease-modifying drug have failed.