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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
NCT00430248.
Becker
Michael A
MA
The University of Chicago Pritzker School of Medicine, MC0930, University of Chicago Medical Center, 5841 S, Maryland Avenue, Chicago, IL 60637, USA. mbecker@medicine.bsd.uchicago.edu
Schumacher
H Ralph
HR
Espinoza
Luis R
LR
Wells
Alvin F
AF
MacDonald
Patricia
P
Lloyd
Eric
E
Lademacher
Christopher
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000627:therapeutic use*; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D000069465:Febuxostat; D005260:Female; D006073:Gout / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000453:epidemiology; D006973:Hypertension / Q000453:epidemiology; D033461:Hyperuricemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D007674:Kidney Diseases / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol