Use of febuxostat in the management of gout in the United Kingdom

Gout is the most common cause of inflammatory arthritis worldwide. Despite clinical cure being achievable and multiple evidence-based guidelines having been published, the incidence and prevalence continues to increase and the condition remains undertreated. Concerns regarding allopurinol have limited its use in those with renal impairment. Febuxostat, a novel xanthine oxidase inhibitor requiring no dose adjustment in mild-moderate renal impairment was launched in the United Kingdom (UK) in 2010. We review published data on the efficacy, safety and tolerability of febuxostat and provide an opinion on its place in the management of gout in the UK in the context of other published guidelines. One phase II trial, multiple phase III trials [febuxostat versus allopurinol controlled trial (FACT), APEX, CONFIRMS] and two open-label extension trials have demonstrated febuxostat given at the doses commonly used in UK practice (80 mg, 120 mg) to reduce serum urate more effectively than those receiving fixed-dose allopurinol. Overall adverse event rates were comparable across treatment groups aside from gout flare (more common in febuxostat-treated patients) and concerns regarding cardiovascular toxicity are being further evaluated in two large trials. If the outcomes of these are favourable, we would anticipate a marked increase in the use of febuxostat in the UK market. We would advocate the use of febuxostat to target a serum urate < 0.3 mmol/l (5 mg/dl) as a second-line urate-lowering therapy in patients with hyperuricaemia, and clinical gout in those intolerant of allopurinol, or in those in whose renal function precludes optimal dose escalation to achieve target serum urate. We would advise prophylaxis against gouty flare with colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs), or Cyclo-oxygenase-2 selective NSAID (COXIB) after febuxostat initiation.