Febuxostat is a selective inhibitor of xanthine oxidase, the enzyme that catalyses the metabolism of purines to uric acid.1
Accumulation of uric acid in the blood, leading to the precipitation of urate crystals in joints and tendons, is responsible for the symptoms of gout.
Febuxostat was studied in 2 randomised, double-blind, pivotal trials involving 1834 patients with hyperuricaemia (serum uric acid level ≥480 micromoles per litre) and gout. Both studies showed the drug to be more effective than a fixed dose of 300mg allopurinol once daily at lowering blood uric acid levels.2
The first study (), which enrolled 1072 patients, compared 3 once daily doses of febuxostat (80mg, 120mg and a safety dose of 240mg) with placebo and allopurinol over a 6-month period.3 The second study () compared 2 doses of febuxostat (80mg and 120mg once daily) with allopurinol over 1 year in 762 patients.4
Allopurinol was administered at a dose of 300mg once daily in both studies, except in patients with mild or moderately impaired renal function, who received 100mg daily in the APEX study and were excluded from the FACT study.
Febuxostat has not been studied in patients with severe renal impairment. All participants also received either colchicine or naproxen for the first 8 weeks, to prevent gout flares.
The primary efficacy endpoint was the number of patients whose final three monthly blood uric acid measurements were below 357 micromoles per litre.
In the APEX study, 48 per cent of patients taking febuxostat 80mg and 65 per cent of patients taking febuxostat 120mg had uric acid levels below 357 micromoles per litre on the final three occasions. This was compared with 22 per cent of the patients taking allopurinol and none of the patients taking placebo (p<0.05 for all comparisons). After the 8 eight weeks of treatment, the proportions of patients who required treatment for gout flares were similar in all the groups.
Median tophus area decreased by a comparable amount in each group.3
Similar results were seen in the FACT study. After 1 year, the proportion of patients who achieved the target uric acid level was 53 per cent in the febuxostat 80mg group and 62 per cent in the febuxostat 120mg group, compared with 21 per cent of the patients in the allopurinol group (p<0.001 for both comparisons). There were no significant differences between any of the groups in the rate of gout flare or the median reduction in tophus area.4
The most common adverse effects associated with febuxostat are liver function abnormalities, diarrhoea, headache, nausea and rash. There may also be an increased risk of cardiovascular effects; therefore, febuxostat is not recommended in patients with ischaemic heart disease or congestive heart failure.1
The recommended dose of febuxostat is 80mg once daily, increasing to 120mg once daily if uric acid levels remain elevated after 2–4 weeks. As with allopurinol, gout flares can still occur during initial treatment as a result of urate mobilisation from tissue deposits. Consequently, concomitant use of colchicine or an NSAID is recommended for at least the first six months of treatment. Febuxostat should not be initiated during an acute attack of gout.1
Febuxostat is approved by NICE as an option for the management of chronic hyperuricaemia in gout if allopurinol is not tolerated or contraindicated.5
Further information: A. Menarini