The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial

• Published in: Arthritis research & therapy Vol. 12; no. 2; p. R63
• Main Authors: Becker, Michael A, Schumacher, H Ralph, Espinoza, Luis R, Wells, Alvin F, MacDonald, Patricia, Lloyd, Eric, Lademacher, Christopher
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.04.2010; BioMed Central
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol - therapeutic use; Care and treatment; Clinical trials; Comorbidity; Dose-Response Relationship, Drug; Drug therapy; Febuxostat; Female; Gout; Gout - blood; Gout - drug therapy; Gout - epidemiology; Gout Suppressants - therapeutic use; Humans; Hyperlipidemias - epidemiology; Hypertension - epidemiology; Hyperuricemia; Hyperuricemia - blood; Hyperuricemia - drug therapy; Hyperuricemia - epidemiology; Kidney Diseases - epidemiology; Male; Management; Middle Aged; Obesity - epidemiology; Research article; Thiazoles - therapeutic use; Treatment Outcome; United States - epidemiology; Uric Acid - blood; Uric acid metabolism; Young Adult; United States
• ISSN: 1478-6354; 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/ar2978

The purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) > or = 8.0 mg/dL in a six-month trial. Subjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment). Endpoints included the proportion of all subjects with sUA <6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA <6.0 mg/dL. Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death. Comorbidities included: renal impairment (65%); obesity (64%); hyperlipidemia (42%); and hypertension (53%). In febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, primary endpoint was achieved in 45%, 67%, and 42%, respectively. Febuxostat 40 mg UL was statistically non-inferior to allopurinol, but febuxostat 80 mg was superior to both (P < 0.001). Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg (72%; P < 0.001) compared with febuxostat 40 mg (50%) or allopurinol (42%), but febuxostat 40 mg showed greater efficacy than allopurinol (P = 0.021). Rates of AEs did not differ across treatment groups. Adjudicated (APTC) CV event rates were 0.0% for febuxostat 40 mg and 0.4% for both febuxostat 80 mg and allopurinol. One death occurred in each febuxostat group and three in the allopurinol group. Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol (300/200 mg), which were comparable. In subjects with mild/moderate renal impairment, both febuxostat doses were more efficacious than allopurinol and equally safe. At the doses tested, safety of febuxostat and allopurinol was comparable. NCT00430248.