title: Clinical efficacy and safety of successful longterm urate lowering with febuxostat or allopurinol in subjects with gout.
abstract: OBJECTIVE
  To determine longterm urate-lowering efficacy and clinical benefits and safety of therapy with febuxostat or allopurinol in subjects with gout.
  
  
  METHODS
  Subjects (n=1086) in this open-label extension study were assigned to fixed-dose daily urate-lowering treatment (ULT) with febuxostat (80 mg or 120 mg) or allopurinol (300 mg). ULT reassignment was permitted during months 1 to 6 to achieve serum urate (SUA) concentrations between 3.0 and <6.0 mg/dl. Flares requiring treatment, tophus size, safety, and SUA levels were monitored during up to 40 months of ULT maintenance.
  
  
  RESULTS
  After 1 month initial treatment, >80% of subjects receiving either febuxostat dose, but only 46% of subjects receiving allopurinol, achieved SUA<6.0 mg/dl. After ULT reassignment, >80% of all remaining subjects maintained the primary efficacy endpoint of SUA<6.0 mg/dl at each visit. More subjects initially randomized to allopurinol required ULT reassignment to achieve SUA<6.0 mg/dl compared with subjects receiving febuxostat. Maintenance of SUA<6.0 mg/dl resulted in progressive reduction to nearly 0 in proportion of subjects requiring gout flare treatment. Baseline tophus resolution was achieved by 46%, 36%, and 29% of subjects maintained on febuxostat 80 mg, febuxostat 120 mg, and allopurinol, respectively. Overall adverse event rates (including cardiovascular adverse event rates), adjusted for 10-fold greater febuxostat than allopurinol exposure, did not differ significantly among treatment groups.
  
  
  CONCLUSIONS
  Durable maintenance of goal range SUA level with either dose of febuxostat or in smaller numbers of subjects with allopurinol resulted in near elimination of gout flares and improved tophus status over time. Registered as NCT00175019.
authors.affiliation: University of Chicago Medical Center, Pritzker School of Medicine, 5841 S. Maryland Ave., Chicago, IL 60637, USA. mbecker@medicine.bsd.uchicago.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Becker
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.forename: Patricia A
authors.initials: PA
authors.lastname: MacDonald
authors.forename: Eric
authors.initials: E
authors.lastname: Lloyd
authors.forename: Christopher
authors.initials: C
authors.lastname: Lademacher
mesh_terms: D000493:Allopurinol / Q000627:therapeutic use*; D000069465:Febuxostat; D006073:Gout / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006074:Gout Suppressants / Q000097:blood / Q000627:therapeutic use*; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood*
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol