Febuxostat: new drug. Hyperuricaemia: risk of gout attacks

(1) For patients with chronic symptomatic hyperuricaemia who fail to respond to a low purine diet, allopurinol is the standard drug used to prevent complications. This xanthine oxidase inhibitor can, in rare instances, cause severe skin reactions. Probenecid, a uricosuric agent, with which there is also long experience, is a second-line option; (2) Febuxostat, another xanthine oxidase inhibitor, is now authorized for the treatment of hyperuricaemia; (3) Two randomised double-blind trials in 762 and 1072 patients tested various doses of febuxostat compared with a standard dose of allopurinol (33 mg/day). Febuxostat normalised uric acid levels more frequently than allopurinol. However, overall, more patients suffered gout attacks with febuxostat than with allopurinol during the first two months of treatment, despite preventive measures (30-35% versus 22%). Between 3 and 6 months of treatment neither drug reduced the incidence of gout attacks more effectively than placebo. After one year of treatment about two-thirds of patients suffered gout attacks, with no difference between the febuxostat and allopurinol groups; (4) In these trials there were more premature treatment withdrawals with febuxostat than with allopurinol; (5) The adverse effects of febuxostat are poorly documented, especially cardiac, hepatic, haematological and thyroid disorders. In the short term, severe cardiac disorders, based on a composite endpoint, were 4 to 5 times more frequent with febuxostat than with allopurinol. Treatment withdrawals due to hepatic disorders were more frequent with febuxostat than with allopurinol (2.8% versus 0.4%). The relative frequency of severe cutaneous disorders with febuxostat and allopurinol is not known; (6) Clinical evaluation does not include any head-to-head trials of febuxostat versus probenecid; (7) In practice, patients with hyperuricaemia should continue to receive allopurinol as first-line treatment, and probenecid as second-line treatment if allopurinol is ineffective.