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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.
Reference:
N Engl J Med. 2005 Dec 8;353(23):2450-61 |