OP0007 A SAFETY AND EFFICACY CLINICAL TRIAL OF A NOVEL NON-PURINE SELECTIVE INHIBITOR OF XANTHINE OXIDASE, FEBUXOSTAT IN SUBJECTS WITH GOUT
M.A. Becker, H. Schumacher Jr, R.L. Wortmann, N. Joseph-Ridge, C. Lademacher

Currently, allopurinol is the only approved drug for treating gout. In this study, Lademacher, et al report safety and efficacy results of a phase II trial with a novel xanthine oxidase inhibitor, febuxostat.

Methods: 153 patients at 24 centers diagnosed with gout and with a baseline serum uric acid (SUA) level of >8mg/dL were randomized to one of four treatment groups: placebo, febuxostat 40mg QD, 80mg QD, or 120mg QD for four weeks. Colchicine 0.6mg twice daily was permitted two weeks prior to start of study and during the first week of treatment. The patients were not on any special diet. The primary endpoint was a SUA < 6mg/dl.

Results: At day 28, the proportions of patients with SUA < 6 mg/dl were 0%, 56%, 76%, and 94% for the placebo, febuxostat 40mg, 80mg, and 120mg groups, respectively. The mean percent decrease in SUA levels from baseline were 2%, 37%, 44%, and 59% in the placebo, and febuxostat 40mg, 80mg, and 120mg, respectively.

Gout flares occurred more frequently in all the febuxostat groups, compared to the placebo, and were increased in all groups following discontinuation of concomitant colchicine; placebo (34%), febuxostat 40mg (30%), febuxostat 80mg (40%) and febuxostat 120mg (42%). The incidence of adverse events was similar for all the patients receiving febuxostat (54%) and comparable to placebo (50%). The most frequently reported adverse events were diarrhea, pain, back pain, headache, and arthralgia.

Conclusion: After one month of treatment, febuxostat significantly reduced serum uric acid levels compared to placebo. Concomittant colchicine proved beneficial in reducing the number of gout flares.

Editorial Comments: This is the first study in decades of a potential new drug for gout and one of the few ever placebo-controlled treatment trials in gout. The increased flares in the febuxostat-treated groups are consistent with our clinical experience in initiation of allopurinol therapy. The critical questions to be answered in future studies with this drug are:

1. does the lowering of SUA<6 result in a profound decrease in gout flares during long-term treatment?
2. will febuxostat be an effective and safe alternative to allopurinol in patients who have hypersensitivity reactions to allopurinol?

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