Superiority of low-dose benzbromarone to low-dose febuxostat in a prospective, randomized comparative effectiveness trial in gout patients with renal uric acid underexcretion.

OBJECTIVE: The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion, yet the standard urate-lowering therapy (ULT) recommendation is first line xanthine oxidase inhibition (XOI) irrespective of the cause of hyperuricemia. Here, we conducted a comparative effectiveness clinical trial of first line un-titrated, low-dose benzbromarone uricosuric therapy vs. XOI ULT with low-dose febuxostat in gout with renal uric acid underexcretion.

METHODS: A prospective, randomized, single-center, open-labeled trial of men with gout and renal uric acid underexcretion (defined as fractional excretion of urate <5.5% and uric acid excretion ≤600 mg/day/1.73m2 ) was conducted. We randomly assigned 196 participants to low-dose benzbromarone 25 mg daily (LDBen) or low-dose febuxostat 20 mg daily (LDFeb) for 12 weeks. All participants received daily urine alkalization with oral sodium bicarbonate. The primary endpoint was rate of achieving serum urate (SU) target <6 mg/dL.

RESULTS: More participants in the LDBen group achieved the serum urate target than LDFeb (61% vs. 32%, P<0.001). Adverse events, including gout flares and urolithiasis, did not differ between groups, with the exception of more transaminase elevation in the LDFeb group (LDBen 4% vs. LDFeb 15%, P=0.008).

CONCLUSION: Compared to LDFeb, LDBen had superior urate-lowering and similar safety in the relatively young and healthy patients with gout of renal uric acid underexcretion type.