Existing and Emerging Therapies for Acute Gout and Long-Term Urate Lowering

Abstract

Untreated or inadequately treated gout results in recurrent acute gouty attacks (one of the most painful forms of acute arthritis), progressive joint damage, formation of tophi, loss of function and disability. The management of gout comprises several key areas. Firstly an accurate diagnosis is required, secondly, long-term urate lowering is required to dissolve monosodium urate crystals and prevent recurrent attacks and subsequent joint damage and disability, thirdly adequate prophylaxis against acute attacks during the introduction of urate lowering therapy is required and finally acute attacks need to be rapidly and effectively controlled. Therapies for acute attacks include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids or colchicine. The choice of agent depends on the presence of co-existing medical conditions and therapies. Early institution of therapy is critical to prompt resolution of acute gout. The goal of prophylactic therapy is sustained reduction of serum urate < 6mg/dL the minimum concentration required to dissolve monosodium urate crystals and to reliably prevent crystal precipitation. This “treat-to-target” approach is being increasingly practised. Allopurinol, which prevents the production of uric acid, is the most widely used agent. Alternatives include the uricosuric drugs, probenecid and benzbromarone. Each has its limitations and novel therapies have recently been developed. These include anti-interleukin-1 (acute gout), and febuxostat and the recombinant uricases (chronic tophaceous gout). This review will examine existing and emerging therapies in the management of gout. Keywords: Gout, urate lowering therapy, chronic tophaceous gout, Non-steroidal anti-inflammatories, cyclooxygenase, pro-inflammatory eicosanoids prostaglandin, prostacyclin, thromboxane, cyclo-oxygenase, Colchicine, erythromycin