INTRODUCTION:This 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout. METHODS:Eligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs). RESULTS:The per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of - 10% (44.7 vs. 50.0%; - 5.3% difference; 95% confidence interval [CI]: - 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently. CONCLUSIONS:Using a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout. TRIAL REGISTRATION:JapicCTI-132106. FUNDING:Astellas Pharma Global Development, Inc.

To retrospectively analyze the efficacy and safety of febuxostat on gout patients with low serum uric acid level. A study was conducted in Nanjing First Hospital from October 2015 to September 2016. Thirty nine acute gouty arthritis patients from the emergency and outpatient department were included. Patients met the 2015 Gout Classification Criteria revised by American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and had urate deposition around the joints detected by dual-energy computerized tomography (DECT). Patients whose serum uric acid (SUA) were between 5.0 and 7.0 mg/dl (300-420 μmol/l) received febuxostat treatment to maintain the SUA level between 3.0 and 5.0 mg/dl for 1 year. Efficacy and safety of febuxostat were observed during the process. Three of 39 subjects were excluded because of adverse events (AEs) after receiving an initial febuxostat treatment for 2 months. Thirty six subjects were enrolled. The mean SUA level was reduced significantly from 6.51 ± 0.28 mg/dl at baseline to 4.24 ± 0.38 mg/dl and SUA of all subjects decreased by 34.8% compared with baseline. After 1-year treatment, the volume of tophus was reduced approximately 62.8%. Serum creatinine decreased stepwise in 8 gout patients with chronic kidney diseases from 162.5 ± 9.2 μmol/l to 131.4 ± 11.0 μmol/l. Two months after initiation of treatment, the number of gout flares began to markedly decrease and almost did not occur after 1 year. After the 1-year treatment of febuxostat, the average SUA level declined significantly, and the renal function improved gradually. There was nearly complete abolition of gout flares by the end of the study. Tophi resolved markedly compared with baseline as assessed by DECT. Furthermore, only a few people experienced adverse events. Febuxostat has a notable effect for gout patients in the lower SUA level range.