title: Febuxostat in gout: serum urate response in uric acid overproducers and underexcretors.
abstract: OBJECTIVE
  Hyperuricemia of gout can arise due to either overproduction or underexcretion of uric acid. Not all available urate-lowering therapies are equally effective and safe for use in patients with renal disease. The objective of this post-hoc analysis was to determine the effectiveness of the xanthine oxidase inhibitor febuxostat in reducing serum urate (sUA) levels in gouty patients who were either overproducers or underexcretors.
  
  
  METHODS
  Gouty subjects 18 to 85 years of age with sUA ≥ 8.0 mg/dl at baseline were enrolled in a Phase 2, 28-day, multicenter, randomized, double-blind, placebo-controlled trial and randomized to receive febuxostat 40 mg, 80 mg, or 120 mg daily, or placebo. The primary efficacy endpoint was the proportion of subjects with sUA < 6.0 mg/dl at Day 28. Secondary efficacy endpoints included percentage reductions in sUA and urinary uric acid (uUA) from baseline to Day 28.
  
  
  RESULTS
  Of the 153 subjects, 118 (77%) were underexcretors (uUA ≤ 800 mg/24 h) and 32 (21%) were overproducers (uUA > 800 mg/24 h); baseline uUA data were missing for 3 subjects. Treatment with febuxostat led to the majority of subjects achieving sUA < 6.0 mg/dl at Day 28. Treatment with any dose of febuxostat led to significantly greater percentage reductions in uUA than that observed in the placebo group, for both underexcretors and overproducers.
  
  
  CONCLUSIONS
  Febuxostat is a highly efficacious urate-lowering therapy in patients with gout regardless of overproduction or underexcretion status.
authors.affiliation: New York Veterans Affairs Medical Center, New York, NY, USA. david.goldfarb@nyumc.org
authors.forename: David S
authors.initials: DS
authors.lastname: Goldfarb
authors.forename: Patricia A
authors.initials: PA
authors.lastname: MacDonald
authors.forename: Barbara
authors.initials: B
authors.lastname: Hunt
authors.forename: Lhanoo
authors.initials: L
authors.lastname: Gunawardhana
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D000069465:Febuxostat; D005260:Female; D006073:Gout / Q000188:drug therapy* / Q000378:metabolism; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism* / Q000652:urine*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D014969:Xanthine Oxidase