Etanercept Structure and Mechanism of Action of Etanercept - Term Paper Example

ETANERCEPT Etanercept is a recombinant human protein that is the first Food and Drug Administration (FDA) approved treatment for psoriatic arthritis (Goffe, 2003). Common Tradename Enbrel C l a s s Immune Suppressant Tumor Necrosis Factor Inhibitor (Thomson MICROMEDEX). Indications Rheumatoid Arthritis (RA): For reduction in signs and symptoms and inhibiting the progression of structural damage in moderately to severe active RA. Polyarticular-course juvenile rheumatoid arthritis (JRA): For reducing signs and symptoms of moderately to severe active polyarticular-course JRA in patients who have had an inadequate response to 1 or more disease - modifying antirheumatic drugs (DMARD). Psoriatic arthritis: For reducing signs and symptoms of active arthritis. It can be used in combination with methotrexate (MTX) in patients who do not respond adequately to MTX alone Unlabelled uses: Psoriasis, ankylosing spondylitis, juvenile spondyloarthropathies. Dosage Adults: The recommended dosage of etanercept for adult patients with RA or psoriatic arthritis is 25mg given twice weekly as an SC injection, 72 to 96 hours apart. MTX, glucocorticoids, salicylates, non-steroidal anti-inflammatory drugs (NSAIDS), or analgesics may be continued during treatment. Doses higher than 25 mg twice weekly are not recommended. Children (4 to 17 years of age): The recommended dose of etanercept for children 4 to 17 years of age with active polyarticular-course JRA is 0.4 mg/kg (upto a maximum of 25 mg/dose). Given SC twice weekly 72 to 96 hours apart. Glucocorticoids, NSAIDS, or analgesics may be continued during treatment with etanercept. Adverse Reactions Etanercept has been studied in approximately 1200 patients with RA, followed for up to 36 months and in 157 patients with psoriatic arthritis for 6 months. The proportion of patients who discontinued treatment because of adverse events was approximately 4% in etanercept and placebo treated patients. The vast majority of these patients were treated with recommended dose 25 mg SC twice daily. In controlled trials of RA and psoriatic arthritis, rates of serious adverse events were seen at a frequency of approximately 5% among etanercept - and control -treated patients. Among RA patients in placebo-controlled, active-controlled, and open-label trials of etanercept, malignancies and infections were the most common serious adverse events observed. Other infrequent serious adverse events observed in RA and psoriatic arthritis clinical trials included the following : Heart failure; MI; myocardial ischemia ; cerebral ischemia ; hypertension ; hypotension ; cholecystitis ; pancreatitis ; GI hemorrhage ; bursitis ; depression ; dyspnea ; deep vein thrombosis ; pulmonary embolism; membranous glomerulonephropathy ; polymyositis and thrombophlobitis. The following serious adverse events were observed in the 50 mg twice weekly arm: GI bleeding, normal pressure hydrocephalous, seizure, and stroke. No serious adverse events were observed in the 25 mg arm (Kastrup, et al., 2003) Etanercept Structure and Mechanism of Action Etanercept is a fully human dimeric fusion protein consisting of the extra cellular ligand-binding domain of the 75 kilodalton (kDa). TNF- receptor linked to the Fc portion of human immunoglobulin G1 (IgG1). Despite the presence of an Fc region, etanercept does not promote complement-mediated lysis in vitro. Etanercept has been shown to have a very low ( Read More