Benzbromarone is not approved in the United States because of concerns of acute liver injury but is approved in several other countries, including China, Brazil, and New Zealand.
“The results suggest that low dosing of benzbromarone may warrant stronger consideration as a safe and effective therapy to achieve serum urate target in gout without moderate chronic kidney disease,” the study team writes.
“Benzbromarone is severely hepatotoxic in some individuals and unlikely to ever gain approval in the United States,” one of the study’s investigators, Robert Terkeltaub, MD, professor of medicine, University of California, San Diego, told this news organization.
However, this study “illustrates the value and impact of uricosuric therapy in general in gout, including potentially as an initial urate-lowering monotherapy strategy, and the sheer number of subjects reaching urate target with low-dose uricosuric monotherapy was impressive,” Dr. Terkeltaub said.
The study was published online in Arthritis & Rheumatology.
“Renal uric acid underexcretion is the chief mechanism driving hyperuricemia in gout, yet the standard urate-lowering therapy recommendation is first-line xanthine oxidase inhibition irrespective of the cause of hyperuricemia,” the study team explains in their article.
Their prospective, randomized, single-center, open-labeled trial was conducted at the Gout Clinic of the Affiliated Hospital of Qingdao University, China.
A total of 196 relatively young healthy men with gout and uric acid underexcretion were randomly assigned to receive low-dose benzbromarone (25 mg/d) or low-dose febuxostat (20 mg/d) for 12 weeks.
Renal uric acid underexcretion was defined as fractional excretion of urate less than 5.5% and uric acid excretion less than or equal to 600 mg/d/1.73 m2.
A “major aspect” of this comparative effectiveness trial was its specific focus on gout-associated renal uric acid underexcretion, where the uricosuric targeted the dominant abnormality promoting the hyperuricemia, Dr. Terkeltaub told this news organization.
In addition, all participants received daily urine alkalinization with oral sodium bicarbonate. “This is not always done in clinical practice, nor in clinical trials of uricosuric agents,” Dr. Terkeltaub said.
The results showed that more participants in the benzbromarone group achieved the serum urate target of less than 6 mg/dL, compared with those in the febuxostat group (primary endpoint, 61% vs. 32%, P < .001).
Adverse events, including gout flares and urolithiasis, did not differ significantly between the two groups, with the exception of more transaminase elevation in the febuxostat group (15% vs. 4%; P = .008).
“We did not find severe hepatotoxicity with low-dose benzbromarone, but ethnic background may affect drug responses, and severe hepatotoxicity of benzbromarone has rarely been reported in Asia,” the authors write.
The incidence of urolithiasis was numerically, but not significantly, higher in the benzbromarone group (5% vs. 2%).
This study found no significant changes in participants’ triglyceride levels, though a previous study suggested febuxostat could increase serum triglycerides.
The investigators caution that the study only included patients who had baseline serum urate levels ranging from 8.0 to 10 mg/dL, who were relatively young and with few comorbidities.
The authors further noted that the “... results may not be generalizable to patients with higher serum urate levels or impaired kidney function, as well [as] patients from other geographical regions, age, and ethnicity groups. The study only included men, and the findings may not be generalizable to women with gout.”