Febuxostat is a non-purine selective inhibitor of xanthine oxidase, an enzyme involved in the final steps of purine metabolism and, ultimately, in the formation of urate. It has been submitted for a European licence for the management of hyperuricaemia in patients with gout. No information is available regarding the proposed dose. Doses used in phase III studies have usually ranged from 80mg to 120mg daily and, therefore, these are the doses that might be expected to be used in clinical practice.

The efficacy of febuxostat in the prevention of gout has been assessed in a phase II placebo-controlled study (n=153), two phase III studies vs. allopurinol (n=762 and 1067), and two long-term, open-label extension studies (n=116 and 1086). The majority of data are presented in abstract form. In a published 52-week phase III study, more febuxostat recipients achieved the primary endpoint of serum urate concentration (sUA) <0.36mmol/L, compared to allopurinol. However, the fixed- ose regimen employed for allopurinol patients may have introduced bias. Despite the greater effect on sUA, there was no difference between treatments in more clinically important outcomes such as gout flares and tophi reduction (secondary endpoints). See the paragraph below for a discussion on the incidence of recurrent gout with febuxostat.

The adverse event profiles of febuxostat and allopurinol were similar over the 52-week period, although significantly more febuxostat recipients withdrew from therapy prematurely. Reasons for withdrawal included gout flares and adverse events such as liver function test abnormalities. The higher incidence of gout flares with febuxostat 120mg per day (during initial prophylaxis with colchicine or naproxen, and on their withdrawal), would be expected to lead to compliance issues, although data suggest the incidence of flares may be reduced by starting at lower doses of febuxostat. Long-term adverse event data for febuxostat are limited.

The overall prevalence of gout in the UK in 1999 was 1.4%, although it has been suggested that gout will become more common due to an ageing population, increasing obesity and lifestyle changes. Prevalence is higher in men and the elderly, so the need for preventative agents will vary according to the demographics of the local population. Not all patients with occasional attacks of gout will require preventative treatment but, in those patients where it is recommended, allopurinol is the drug of choice. Febuxostat may be an alternative for the 2-4% of patients who cannot tolerate allopurinol, but favourable laboratory results have not yet translated into better clinical outcomes. The drug is likely to be more costly than allopurinol. It is currently unclear how dose titration and monitoring requirements for febuxostat will compare to those for allopurinol, and any additional impact on service delivery is unknown.