Baseline urate level and renal function predict outcomes of urate-lowering therapy using low doses of febuxostat and benzbromarone: a prospective, randomized controlled study in a Chinese primary gout cohort

Abstract

Background Low doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs. Methods To compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software. Results Two hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks’ ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (< 360 μmol/L) and serum urate levels were reduced significantly for both groups (Feb 39.5% and 156.83 μmol/L vs. Ben 35.7% and 163.99 μmol/L). Multivariate analysis suggests baseline sUA level and renal function were associated with the outcome of the rate of achieving target sUA (RAT). Sub-group analysis suggests low doses of febuxostat and benzbromarone rendered better RAT for patients with sUA < 540 μmol/L and creatinine clearance rate (Ccr) ≤ 110 mL min −1 1.73 m −2 at baseline. The drugs were well tolerated, and the incidence of gout flares in Feb group was similar with that in Ben group (22.85% vs. 33.94%). Conclusion Overall, febuxostat 20 mg daily and benzbromarone 25 mg daily reduced sUA, and gout patients with sUA level < 540 μmol/L or Ccr ≤ 110 mL min −1 1.73 m −2 at baseline had better chance to achieve target uric acid levels. The current study suggests sUA level and renal function are key factors to consider when recommending low doses of febuxostat and benzbromarone to gout patients. Trial registration Registered with ChiCTR, No. ChiCTR1800019352 (retrospectively registered).

Efficacy And Renal Safety of Febuxostat In Management of Gout And Chronic Kidney Disease: A Retrospective Study

“…This level was lower compared with the value reported in previous RCTs whereby the dosage of febuxostat was xed [14,19]. However, it was similar to values reported in Chinese cohort studies on treatment of gout using febuxostat 20~80mg/day, whereby RAT varied from 22.5% to 70% [29][30][31][32]. Furthermore, the ndings from strati cation analysis based on baseline stage of CKD indicate that sUA level in patients with different CKD stages reduced by approximately 140~350 µmol/L, and the RAT level was 24%~50%.…”

Decrease in Serum Urate Level Is Associated With Loss of Visceral Fat in Male Gout Patients

“…A positive statistical association between visceral fat variance and serum urate decrease also was observed after adjustment for potential confounding variables and concomitant medication use (beta, 0.302; p = 0.001). As our previous study showed, SU levels were reduced by ~160 μmol/L in gout patients taking low-dose febuxostat (20 mg/day) or benzbromarone (25 mg/day) within 12 weeks ( 34 ). The ΔSU of Q4 in this study is a clinically relevant decrease and realizable in clinical practice.…”

12-month results from the real-life observational treat-to-target and tight-control therapy NOR-Gout study: achievements of the urate target levels and predictors of obtaining this target

“…Two randomised controlled trials found that baseline sUA was related to the treatment response as measured by sUA. 42 43 Further, healthcare access, patient and provider factors as well as presence of comorbidities were recently reported associated to achieving and maintaining the target sUA level. 44 …”

“…Two randomised controlled trials found that baseline sUA was related to the treatment response as measured by sUA. 42 43 Further, healthcare access, patient and provider factors as well as presence of comorbidities were recently RMD Open RMD Open RMD Open reported associated to achieving and maintaining the target sUA level. 44 Limitations of our study include that patients were entered from only one centre and findings cannot necessarily be extrapolated to other clinical settings.…”