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

被引:393
作者
Becker, Michael A. [1 ]
Schumacher, H. Ralph [2 ,3 ]
Espinoza, Luis R. [4 ]
Wells, Alvin F. [5 ]
MacDonald, Patricia [6 ]
Lloyd, Eric [6 ]
Lademacher, Christopher [7 ]
机构
[1] Univ Chicago, Univ Chicago Pritzker Sch Med, Med Ctr, Chicago, IL 60637 USA
[2] Univ Penn, Philadelphia, PA 19104 USA
[3] VA Med Ctr, Philadelphia, PA 19104 USA
[4] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70115 USA
[5] Rosalind Franklin Univ Med & Sci, Grays Lake, IL 60030 USA
[6] Takeda Global Res & Dev Ctr Inc, Deerfield, IL 60015 USA
[7] Astellas Pharma Global Dev Inc, Deerfield, IL 60015 USA
关键词
SERUM URIC-ACID; QUALITY-OF-LIFE; CREATININE CLEARANCE; CARDIOVASCULAR MORTALITY; ALLOPURINOL; ARTHRITIS; DISEASE; EPIDEMIOLOGY; INHIBITOR; RISK;
D O I
10.1186/ar2978
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: 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) >= 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.
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页数:12
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