Febuxostat Compared with Allopurinol in Patients with Hyperuricemia and Gout
Michael A. Becker, M.D., H. Ralph Schumacher, Jr., M.D., Robert L. Wortmann, M.D., Patricia A. MacDonald, B.S.N., N.P., Denise Eustace, B.A., William A. Palo, M.S., Janet Streit, M.S., and Nancy Joseph-Ridge, M.D.
Background Febuxostat, a novel nonpurine selective inhibitorof xanthine oxidase, is a potential alternative to allopurinolfor patients with hyperuricemia and gout.
Methods We randomly assigned 762 patients with gout and withserum urate concentrations of at least 8.0 mg per deciliter(480 µmol per liter) to receive either febuxostat (80mg or 120 mg) or allopurinol (300 mg) once daily for 52 weeks;760 received the study drug. Prophylaxis against gout flareswith naproxen or colchicine was provided during weeks 1 through8. The primary end point was a serum urate concentration ofless than 6.0 mg per deciliter (360 µmol per liter) atthe last three monthly measurements. The secondary end pointsincluded reduction in the incidence of gout flares and in tophusarea.
Results The primary end point was reached in 53 percent of patientsreceiving 80 mg of febuxostat, 62 percent of those receiving120 mg of febuxostat, and 21 percent of those receiving allopurinol(P<0.001 for the comparison of each febuxostat group withthe allopurinol group). Although the incidence of gout flaresdiminished with continued treatment, the overall incidence duringweeks 9 through 52 was similar in all groups: 64 percent ofpatients receiving 80 mg of febuxostat, 70 percent of thosereceiving 120 mg of febuxostat, and 64 percent of those receivingallopurinol (P=0.99 for 80 mg of febuxostat vs. allopurinol;P=0.23 for 120 mg of febuxostat vs. allopurinol). The medianreduction in tophus area was 83 percent in patients receiving80 mg of febuxostat and 66 percent in those receiving 120 mgof febuxostat, as compared with 50 percent in those receivingallopurinol (P=0.08 for 80 mg of febuxostat vs. allopurinol;P=0.16 for 120 mg of febuxostat vs. allopurinol). More patientsin the high-dose febuxostat group than in the allopurinol group(P=0.003) or the low-dose febuxostat group discontinued thestudy. Four of the 507 patients in the two febuxostat groups(0.8 percent) and none of the 253 patients in the allopurinolgroup died; all deaths were from causes that the investigators(while still blinded to treatment) judged to be unrelated tothe study drugs (P=0.31 for the comparison between the combinedfebuxostat 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 fixeddaily dose of 300 mg in lowering serum urate. Similar reductionsin gout flares and tophus area occurred in all treatment groups.
Source Information
From the University of Chicago Pritzker School of Medicine, Chicago (M.A.B.); the University of Pennsylvania School of Medicine, Veterans Affairs Medical Center, Philadelphia (H.R.S.); the University of Oklahoma Department of Medicine, Tulsa (R.L.W.); and Research and Development, TAP Pharmaceutical Products, Lake Forest, Ill. (P.A.M., D.E., W.A.P., J.S., N.J.-R.).
Address reprint requests to Dr. Becker at MC0930, University of Chicago Medical Center, 5841 S. Maryland Ave., Chicago, IL 60637, or at mbecker{at}medicine.bsd.uchicago.edu.
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