Superiority of low dose benzbromarone add‐on to low dose febuxostat compared to febuxostat monotherapy in gout with combined‐type hyperuricemia

Abstract

ObjectiveThere is unmet need for simpler ULT regimens that achieve serum urate target and improve overall quality of gout care. We report a comparative effectiveness trial of febuxostat monotherapy vs. benzbromarone add‐on to low dose febuxostat in gout specifically with combined renal urate underexcretion and overload.MethodsA prospective, randomized trial was conducted on subjects with a combined type of hyperuricemia and eGFR above 60 ml/min/1.73 m2, 1:1 randomly assigned to febuxostat and benzbromarone combination therapy (initially febuxostat 20mg/day, with benzbromarone 25mg/day added onto 20 mg/day febuxostat if not at target) or febuxostat monotherapy (initially 20mg daily, escalating to 40mg daily if not at target). Primary end point at 12 weeks was proportion achieving serum urate (SU) level < 360μmol/L. Other outcomes included altered liver and kidney function, new‐onset urolithiasis, and gout flares.ResultsThere were 250 participants randomized; with 219 completing 12‐week treatment. More febuxostat and benzbromarone combination group subjects achieved SU target compared to febuxostat monotherapy group subjects (75.5% vs. 47.7%; OR 3.37 [95% CI 1.90, 5.98]). Safety profiles were comparable between the two groups.ConclusionSimply adding on low‐dose benzbromarone (25 mg/day) to low‐dose (20 mg/day) febuxostat showed superior urate lowering to febuxostat monotherapy in gout with a combined‐type hyperuricemia. For selected patients, expedited achievement of serum urate target in over 75% of subjects, using one titration step and low XOI and uricosuric doses, is a potential alternative to standard ULT regimens.This article is protected by copyright. All rights reserved.