Article

Effects of Febuxostat Versus Allopurinol and Placebo in Reducing Serum Urate in Subjects With Hyperuricemia and Gout: A 28-Week, Phase III, Randomized, Double-Blind, Parallel-Group Trial

University of Pennsylvania and VA Medical Center, Philadelphia, PA 19104, USA.
Arthritis & Rheumatology (Impact Factor: 7.76). 11/2008; 59(11):1540-8. DOI: 10.1002/art.24209
Source: PubMed

ABSTRACT

To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.
Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.
Significantly (P < or = 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.
At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.

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    • "Regarding safety, adverse events were similar with febuxostat and allopurinol [Schumacher et al. 2008; Huang et al. 2014; Tausche et al. 2014]. "
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    • "the 17 studies were excluded because they contained duplicate data313233, open-label data343536, or insufficient data373839. Thus, 8 RCTs including 4,099 patients (2,108 events for efficacy and 291 events for safety) met the inclusion criteria89101112131415(Table 1). The evidence network diagram shows data related to the number of studies performed comparing the different treatments, the numbers of patients in each treatment (Table 1and Figure 1). "
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    • "A 6-month, large-scale, RCT of febuxostat 40/80 mg or allopurinol 300 mg (200 mg in moderate renal impairment) was conducted in 2,269 patients with gout and SUA ≥8.0 mg/dL [48]; the study indicated (1) the equivalent UL efficacy and comparable safety for febuxostat 40 mg daily and allopurinol 300/200 mg daily, (2) the significantly greater efficacy of febuxostat 40 mg daily in lowering SUA than allopurinol in patients with mildly or moderately impaired renal function, (3) comparable safety at the doses examined, and (4) the favorable tolerability of febuxostat 40 mg daily, especially for gout patients with mild or moderate renal impairment. The large-scale RCTs of febuxostat conducted to date [45,46,48] reported treatment-related AEs, the majority of which were mild to moderate in severity (e.g., liver function test abnormalities, diarrhea, nausea, headache, joint-related signs and symptoms, and rashes); the major serious AEs were non-specific bacterial infections, coronary artery disease, ischemic coronary artery disorders, and so on. Hence, there is a battery of experimental and clinical evidence to design an RCT in hyperuricemic patients with moderate renal impairment (30–59 mL/min/1.73 "
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