Objective
There is an unmet need for simpler urate‐lowering therapy (ULT) regimens that achieve the serum urate target and improve the overall quality of gout care. We report a comparative effectiveness trial of febuxostat monotherapy versus benzbromarone add‐on to low‐dose febuxostat in gout specifically with combined renal urate underexcretion and overload.
Methods
A prospective randomized trial was conducted on patients with combined‐type hyperuricemia and estimated glomerular filtration rate >60 mL/min/1.73 m2 1:1 randomly assigned to febuxostat and benzbromarone combination therapy (initially febuxostat at 20 mg/day, with benzbromarone at 25 mg/day added onto 20 mg/day of febuxostat if not at target) or febuxostat monotherapy (initially 20 mg/day, escalating to 40 mg/day if not at target). The primary end point at 12 weeks was the proportion achieving a serum urate (SU) level <360 μmol/L. Other outcomes included altered liver and kidney function, new‐onset urolithiasis, and gout flares.
Results
There were 250 participants randomized; 219 completed 12‐week treatment. More patients in the febuxostat and benzbromarone combination group achieved the SU target compared to patients in the febuxostat monotherapy group (75.5% vs 47.7%; odds ratio 3.37 [95% confidence interval 1.90–5.98]). Safety profiles were comparable between the two groups.
Conclusion
Simply adding on low‐dose benzbromarone (25 mg/day) to low‐dose (20 mg/day) febuxostat showed superior urate lowering compared to febuxostat monotherapy in gout with a combined‐type hyperuricemia. For selected patients, expedited achievement of the SU target in more than 75% of patients using one titration step and low xanthine oxidase inhibitor and uricosuric doses is a potential alternative to standard ULT regimens.