A key objective of long-term management of gout is “cure”. This can be achieved by patient education, modification of the patient's risk factors (diet, obesity, hypertension, lipid levels), and by maintaining tissue urate levels below the saturation point for crystal formation (serum uric acid <360 μmol/l or 6 mg/dl) [Zhang W et al. Ann Rheum Dis 2006].

The purine xanthine oxidase inhibitor allopurinol is the most widely used urate-lowering therapy (ULT) and offers a wide-dose range for individual dose titration. Allopurinol administered 100–900 mg daily inhibits xanthine oxidase, and thus uric acid formation. Its principal drawback is allopurinol “hypersensitivity” syndrome which is more common in patients with renal impairment. Although rare, it can prove fatal.

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout. At a daily dose of 80 or 120 mg, febuxostat was more effective than a standard fixed dose of allopurinol (300 mg/day) in lowering serum urate after 1 year (Becker MA et al. N Engl J Med 2005). Febuxostat is awaiting regulatory clearance in Europe. Because of its efficiency at the doses that will be available (80mg and 120mg), prophylaxis of acute attacks is recommended when initiating therapy.

Uricosurics (sulphinpyrazone, probenecid, benzbromarone) have limited availability and are contraindicated, and less effective, in patients with renal impairment. Uricosurics predominantly act on urate transporter 1 (URAT-1) in the proximal renal tubule. Benzbromarone is a very efficient urate lowering agent, even in patients with mild-moderate renal impairment, but because of rare hepatotoxicity its use has been restricted. Therefore, other ULTs are being examined. Losartan and fenofibrate cause modest reductions in serum uric acid (20–40%) via a uricosuric effect and can be adjunctive agents in gout patients that require treatment for hypertension or lipid reduction [Bardin T. Ann Rheum Dis 2003]. Supplementation with 500mg ascorbate/day can reduce serum uric acid in hyperuricaemic patients by close to 20% [Huang H-Y et al. Arthritis Rheum 2005], again through a uricosuric effect.

Humans lack uricase, the urate oxidase enzyme that converts uric acid to allantoin. When given intravenously uricase can reduce serum uric acid levels to nearly zero. There are reports of dramatic reduction in tophi using Rasburicase (a pegylated form of Aspergillus-derived uricase licensed for tumour lysis syndrome), but immunogenicity limits its repeated use. Therefore, there are current efforts to develop a less immunogenic form of mammalian uricase for repeated use in gout [Ganson NJ et al. Arthritis Res Ther 2006].

There are recent data from the UK showing that a minority of gout patients receive education, including dietary and other lifestyle advice and that only approximately one third are given ULT [Mikuls TR et al. Ann Rheum Dis 2005; Roddy et al. Ann Rheum Dis 2007. In press]. Of these, almost all are on allopurinol at a standard dose of 300mg/day, which is an insufficient dose for many patients, meaning that the majority of gout patients do not experience “cure” [Roddy et al]. Therefore education on the principles of long-term gout management and optimization of currently available treatments alone could have a major impact on improving the outcome of this common, painful, inflammatory arthritis.