title: The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age.
abstract: BACKGROUND
  The incidence of gout rises with increasing age. Management of elderly (≥65 years) gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT) in the elderly. The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial.
  
  
  METHODS
  Hyperuricemic (serum urate [sUA] levels ≥ 8.0 mg/dL) gout subjects were enrolled in the 6-month, double-blind, randomized, comparative CONFIRMS trial and randomized, 1:1:1, to receive febuxostat, 40 mg or 80 mg, or allopurinol (200 mg or 300 mg based on renal function) once daily. Flare prophylaxis was provided throughout the study duration.Study endpoints were the percent of elderly subjects with sUA <6.0 mg/dL at the final visit, overall and by renal function status, percent change in sUA from baseline to final visit, flare rates, and rates of adverse events (AEs).
  
  
  RESULTS
  Of 2,269 subjects enrolled, 374 were elderly. Febuxostat 80 mg was significantly more efficacious (82.0%) than febuxostat 40 mg (61.7%; p < 0.001) or allopurinol (47.3%; p < 0.001) for achieving the primary efficacy endpoint. Febuxostat 40 mg was also superior to allopurinol in this population (p = 0.029). In subjects with mild-to-moderate renal impairment, significantly greater ULT efficacy was observed with febuxostat 40 mg (61.6%; p = 0.028) and febuxostat 80 mg (82.5%; p < 0.001) compared to allopurinol 200/300 mg (46.9%). Compared to allopurinol 200/300 mg, the mean percent change in sUA from baseline was significantly greater for both febuxostat 80 mg (p < 0.001) and febuxostat 40 mg (p = 0.011) groups. Flare rates declined steadily in all treatment groups. Rates of AEs were low and comparable across treatments.
  
  
  CONCLUSIONS
  These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol (200/300 mg) in subjects ≥65 years of age with high rates of renal dysfunction. In addition, in this high-risk population, ULT with either drug was well tolerated.
  
  
  BACKGROUND
  clinicaltrials.gov NCT#00430248.
authors.affiliation: Takeda Global Research & Development Centers, Inc, One Takeda Parkway, Deerfield, Illinois 60015, USA. Robert.Jackson@takeda.com
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jackson
authors.forename: Barbara
authors.initials: B
authors.lastname: Hunt
authors.forename: Patricia A
authors.initials: PA
authors.lastname: MacDonald
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004311:Double-Blind Method; D000069465:Febuxostat; D005260:Female; D006073:Gout / Q000097:blood* / Q000188:drug therapy*; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014527:Uric Acid / Q000037:antagonists & inhibitors* / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D015415:Biomarkers; D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D014969:Xanthine Oxidase