Impact of Febuxostat on Renal Function in Gout Patients With Moderate-to-Severe Renal Impairment

Arthritis Rheumatol. 2016 Aug;68(8):2035-43. doi: 10.1002/art.39654.

Abstract

Objective: Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73 m(2) ).

Methods: Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1:1:1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12.

Results: At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses.

Conclusion: Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function.

Trial registration: ClinicalTrials.gov NCT01082640.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Febuxostat / therapeutic use*
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Gout / complications*
  • Gout / drug therapy*
  • Gout Suppressants / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Insufficiency / complications*
  • Renal Insufficiency / physiopathology*
  • Severity of Illness Index

Substances

  • Gout Suppressants
  • Febuxostat

Associated data

  • ClinicalTrials.gov/NCT01082640