Superiority of Low‐Dose Benzbromarone to Low‐Dose Febuxostat in a Prospective, Randomized Comparative Effectiveness Trial in Gout Patients With Renal Uric Acid Underexcretion

Abstract

Objective. The predominant mechanism driving hyperuricemia in gout is renal uric acid underexcretion; however, the standard urate-lowering therapy (ULT) recommendation is first-line xanthine oxidase inhibitor (XOI), irrespective of the cause of hyperuricemia. This comparative effectiveness clinical trial was undertaken to compare first-line nontitrated low-dose benzbromarone (LDBen) uricosuric therapy to XOI ULT with low-dose febuxostat (LDFeb) in gout patients with renal uric acid underexcretion.Methods. We conducted a prospective, randomized, single-center, open-label trial in men with gout and renal uric acid underexcretion (defined as fractional excretion of urate <5.5% and uric acid excretion ≤600 mg/day/1.73 m 2 ). A total of 196 participants were randomly assigned to receive LDBen 25 mg daily or LDFeb 20 mg daily for 12 weeks. All participants received daily urine alkalization with oral sodium bicarbonate. The primary end point was the rate of achieving the serum urate target of <6 mg/dl.Results. More participants in the LDBen group achieved the serum urate target than those in the LDFeb group (61% compared to 32%, P < 0.001). Rates of adverse events, including gout flares and urolithiasis, did not differ between groups, with the exception of greater transaminase elevation in the LDFeb group (4% for LDBen compared to 15% for LDFeb, P = 0.008).Conclusion. Compared to LDFeb, LDBen has superior urate-lowering efficacy and similar safety in treating relatively young and healthy patients with renal uric acid underexcretion-type gout.

Superiority of Low‐Dose Benzbromarone Add‐On to Low‐Dose Febuxostat Compared With Febuxostat Monotherapy in Gout With Combined‐Type Hyperuricemia

“…30 Moreover, in a clinical trial of relatively young and healthy people with gout and renal uric acid underexcretion-type hyperuricemia, low-dose benzbromarone had urate-lowering efficacy superior to low-dose febuxostat. 18 These findings reinforce the heterogeneous nature of hyperuricemia in gout and suggest that tailoring treatment according to hyperuricemia type may improve quality of care.…”

“…In a previous trial of people with gout and renal underexcretion–type hyperuricemia, the proportion of participants who achieved an SU level of <360 μmol/L with low‐dose benzbromarone (25 mg) was 61%, 18 and 39.5% achieved an SU level of <360 μmol/L with low‐dose febuxostat (20 mg) 19 . In an initial planned estimate, a total of 109 randomized participants in each group would have achieved 90% power to detect the difference in the proportion of participants achieving an SU level of <360 μmol/L with a significance level of 0.05 using a chi‐square test.…”

Comparison of clinical and economic evaluation between selected generic and original febuxostat tablets in Chinese gout patients with hyperuricemia: A real-world multicenter retrospective study

“…A total of 114 patients enrolled after PSM had at least one comorbid condition, partly because patients admitted to the 3 included top tertiary hospitals in China were relatively severe and febuxostat was widely prescribed in patients with mild to moderate kidney or liver impairment for requiring no dose adjustment. Different from previous studies, [22,23] the target of ULT was set as the endpoint SUA level <300 μmol/L in this study. The results showed that, in a real-world setting, generic febuxostat had similar urate-lowering efficacy at 2, 4, 8, and 12 weeks compared with original febuxostat.…”

Ameliorative Effect of Mannuronate Oligosaccharides on Hyperuricemic Mice via Promoting Uric Acid Excretion and Modulating Gut Microbiota

“…Maintaining the balance of uric acid biosynthesis and excretion is essential for uric acid metabolism. In clinical practice, drugs used to treat hyperuricemia work by inhibiting uric acid synthesis or promoting uric acid excretion, such as allopurinol and febuxostat, which are XOD inhibitors that depress uric acid synthesis [ 50 ], in contrast to benzbromarone and probenecid, which promote uric acid excretion by suppressing URAT1 and GLUT9 [ 51 ]. Uric acid is synthesized in the liver, and XOD and ADA enzymes are key enzymes in the uric acid production pathway.…”