Gout - febuxostat
Gout is an extremely painful condition that is caused by a build up of uric acid in the joints, especially those in the big toes and ankles.
Gout is an extremely painful condition that is caused by a build up of uric acid in the joints, especially those in the big toes and ankles.
This hyperuricaemia occurs when more uric acid is produced by the liver than the body can excrete in the urine, or when a rich diet results in more uric acid than the kidneys are able to filter from the blood. The uric acid crystallises out in the joints, resulting in swelling, inflammation, pain and stiffness.
It can be treated with nonsteroidal anti-inflammatory drugs such as naproxen and indomethacin, or corticosteroids. If these do not help, then colchicine and probenecid can be used, but neither is ideal. A new gout treatment, febuxostat, is being investigated by Teijin, and has been licensed to TAP.1 The selective non-purine inhibitor of xanthine oxidase reduces the formation of uric acid in the body.
A Phase I trial was carried out to evaluate its safety, pharmacological properties and urate lowering efficacy.2 A total of 154 healthy adults were given daily doses of febuxostat in the range of 10 to 120mg over a period of two weeks. Proportional mean serum urate reductions ranged from 25% to 70%. Serum xanthine concentrations also increased, along with a decrease in uric acid excretion. The rare adverse events were mild and self-limiting, and no serious side-effects were seen.
In a Phase II randomised double blind placebo-controlled trial, 153 patients were given 40, 80 or 120mg febuxostat or placebo once a day for 28 days, and colchicine prophylaxis was given for 14 days before and 14 days after randomisation.3 More patients given febuxostat reached their target uric acid levels on day 28 than those given placebo, with 56%, 76% and 94% of those given the three dose levels reaching the target, while none of the placebo group did. The most common adverse events were diarrhoea, pain, back pain, arthralgia and headache.
A multicentre double blind Phase III trial has also been carried out in 256 patients with gout or hyperuricaemia.4 The subjects were randomised to 10mg febuxostat or 100mg allopurinol a day for 12 days. The doses were then increased to 40mg febuxostat or allopurinol twice a day for the next 44 days. Febuxostat gave significantly greater reductions in serum uric acid, and 82% of these reached the target uric acid level, compared with 69% of those given allopurinol. Again, side-effects were minimal.