Febuxostat compared with allopurinol in patients with hyperuricemia and gout.

BACKGROUND: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia and gout. METHODS: We randomly assigned 762 patients with gout and with serum urate concentrations of at least 8.0 mg per deciliter (480 micromol per liter) to receive either febuxostat (80 mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks; 760 received the study drug. Prophylaxis against gout flares with naproxen or colchicine was provided during weeks 1 through 8. The primary end point was a serum urate concentration of less than 6.0 mg per deciliter (360 micromol per liter) at the last three monthly measurements. The secondary end points included reduction in the incidence of gout flares and in tophus area. RESULTS: The primary end point was reached in 53 percent of patients receiving 80 mg of febuxostat, 62 percent of those receiving 120 mg of febuxostat, and 21 percent of those receiving allopurinol (P<0.001 for the comparison of each febuxostat group with the allopurinol group). Although the incidence of gout flares diminished with continued treatment, the overall incidence during weeks 9 through 52 was similar in all groups: 64 percent of patients receiving 80 mg of febuxostat, 70 percent of those receiving 120 mg of febuxostat, and 64 percent of those receiving allopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol; P=0.23 for 120 mg of febuxostat vs. allopurinol). The median reduction in tophus area was 83 percent in patients receiving 80 mg of febuxostat and 66 percent in those receiving 120 mg of febuxostat, as compared with 50 percent in those receiving allopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol; P=0.16 for 120 mg of febuxostat vs. allopurinol). More patients in the high-dose febuxostat group than in the allopurinol group (P=0.003) or the low-dose febuxostat group discontinued the study. Four of the 507 patients in the two febuxostat groups (0.8 percent) and none of the 253 patients in the allopurinol group died; all deaths were from causes that the investigators (while still blinded to treatment) judged to be unrelated to the study drugs (P=0.31 for the comparison between the combined febuxostat groups and the allopurinol group). CONCLUSIONS: Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate. Similar reductions in gout flares and tophus area occurred in all treatment groups.

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout.

OBJECTIVE: Gout affects approximately 1-2% of the American population. Current options for treating hyperuricemia in chronic gout are limited. The purpose of this study was to assess the safety and efficacy of febuxostat, a nonpurine selective inhibitor of xanthine oxidase, in establishing normal serum urate (sUA) concentrations in gout patients with hyperuricemia (>or=8.0 mg/dl). METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled trial in 153 patients (ages 23-80 years). Subjects received febuxostat (40 mg, 80 mg, 120 mg) or placebo once daily for 28 days and colchicine prophylaxis for 14 days prior to and 14 days after randomization. The primary end point was the proportion of subjects with sUA levels <6.0 mg/dl on day 28. RESULTS: Greater proportions of febuxostat-treated patients than placebo-treated patients achieved an sUA level <6.0 mg/dl at each visit (P < 0.001 for each comparison). The targeted sUA level was attained on day 28 in 0% of those taking placebo and in 56% of those taking 40 mg, 76% taking 80 mg, and 94% taking 120 mg of febuxostat. The mean sUA reduction from baseline to day 28 was 2% in the placebo group and 37% in the 40-mg, 44% in the 80-mg, and 59% in the 120-mg febuxostat groups. Gout flares occurred with similar frequency in the placebo (37%) and 40-mg febuxostat (35%) groups and with increased frequency in the higher dosage febuxostat groups (43% taking 80 mg; 55% taking 120 mg). During colchicine prophylaxis, gout flares occurred less frequently (8-13%). Incidences of treatment-related adverse events were similar in the febuxostat and placebo groups. CONCLUSION: Treatment with febuxostat resulted in a significant reduction of sUA levels at all dosages. Febuxostat therapy was safe and well tolerated.