Article

Febuxostat: the evidence for its use in the treatment of hyperuricemia and gout.

Birmingham VA Medical Center.
Core Evidence 01/2010; 4:25-36.
Source: PubMed

ABSTRACT Gout is a common and disabling cause of arthritis in middle-aged and elderly populations, with its main predisposing factor being hyperuricemia (serum urate > 6.8 mg/dL). Options for treatment of chronic gout until 2008 were allopurinol, a xanthine oxidase inhibitor, and the group of drugs known as uricosurics that stimulate the renal excretion of uric acid. A proportion of patients, including some with chronic kidney disease and solid organ transplantations, could not be treated with the those therapies because of intolerance, drug interactions, or adverse events. Febuxostat is a nonpurine xanthine oxidase inhibitor, recently approved in Europe and the United States for the treatment of chronic gout.
To review the clinical evidence (phase II and III studies) of the effectiveness and safety of febuxostat for treatment of hyperuricemia and gout.
Febuxostat, at doses ranging from 40 to 240 mg/day, is efficacious in reducing serum urate in patients with hyperuricemia and gout, comparing favorably with fixed doses of allopurinol in that respect. Early safety signals with respect to liver test abnormalities and cardiovascular outcomes have not been confirmed in recent large prospective trials but need to be further monitored.
Given its low cost and extensive clinical experience, allopurinol will likely remain the first-line drug for management of hyperuricemia and gout. Febuxostat may provide an important option in patients unable to use allopurinol, those with very high serum urate levels, or in the presence of refractory tophi.

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    ABSTRACT: Objective: Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout. Methods: The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales. Results: The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout. Conclusions: The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.
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