Management of rheumatoid arthritis - Defining the role of etanercept

Rheumatoid arthritis is associated with substantial costs to both the individual and society; costs increase as disease severity worsens. Current thinking is that disease-modifying antirheumatic drug (DMARD) therapy should be started as soon as possible after the diagnosis of rheumatoid arthritis and that patients should be offered the most effective treatment available. Etanercept is a soluble dimeric fusion protein comprising two copies of the extracellular ligand-binding domain of the human p75 receptor for tumour necrosis factor-alpha (TNFalpha) linked to the constant portion of human immunoglobulin G1. TNFalpha is thought to play an important role in the pathophysiology of rheumatoid arthritis; by binding the cytokine, etanercept blocks its biologic effects. In a 12-month double-blind, randomized study involving patients with early active rheumatoid arthritis, administration of subcutaneous etanercept 25mg twice weekly was associated with a more rapid and significantly greater overall response (assessed using American College of Rheumatology criteria) than oral methotrexate. In addition, compared with methotrexate, etanercept was associated with more rapid slowing of radiographic progression and a more rapid improvement in measures of health-related quality of life. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept, alone or in combination with methotrexate, also showed sustained efficacy in three double-blind, randomized, placebo-controlled studies of 3 to 6 months' duration involving patients with active rheumatoid arthritis who had not responded adequately to previous treatment with DMARDs. Etanercept was generally well tolerated in clinical trials (the most commonly occurring adverse events included injection site reactions, infection, headache, nausea, rhinitis, dizziness, pharyngitis and cough). The high cost of etanercept relative to traditional DMARDs may be justified if it can be shown to reduce long-term outcomes associated with rheumatoid arthritis, thereby reducing disease costs. Conclusion: Etanercept is an important new treatment option in rheumatoid arthritis. It provides a rapid and sustained reduction in disease activity and inhibits the progression of structural damage in patients with early active rheumatoid arthritis, with good tolerability. The improvement in disease activity and slowing of joint damage seen with etanercept was more rapid than that seen with methotrexate. In addition, etanercept, alone or in combination with methotrexate, is effective in the treatment of patients with active rheumatoid arthritis who have not responded adequately to previous DMARD therapy. It is anticipated that etanercept may also improve the long-term outcome of patients with rheumatoid arthritis and reduce the substantial economic burden imposed by the disease; however, more long-term data are needed to establish this.