Low-Dose Benzbromarone Superior to Low-Dose Febuxostat in Gout Treatment

When compared with a low dose of febuxostat (LDFeb), patients receiving a low-dose of benzbromarone (LDBen) reported better urate-lowering effects, coupled with a similar safety profile, in relatively young and healthy men with gout of renal uric acid and underexcretion type, according to a study published in Arthritis & Rheumatology.¹

“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,” investigators explained.

In this prospective, randomized, single-center, open-labeled trial conducted in the Gout Clinic of the Affiliated Hospital of Qingdao between May 2019 and January 2021, 196 men with gout and uric acid underexcretion were randomly assigned to receive LDBen 25 mg daily or LDFeb 20 mg daily for 12 weeks. Eligible patients had a gout diagnosis according to the 2015 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria, were aged 18 to 70 years, had levels of serum urate (SU) between 7 mg/dL and 10 mg/dL, and renal underexcretion. Baseline information, such as age, disease duration, age at onset, body mass index, lifestyle, family history, and disease history were collected. Other ULTs were prohibited during the study period.

Renal uric acid underexcretion was defined as a fractional excretion of urate <5.5% and uric acid excretion ≤600 mg/day/1.73m2. All patients received daily urine alkalization and oral sodium bicarbonate (1 gram 3 times per day). The primary endpoint was the rate of attaining a SU target <6 mg/dL.

Ultimately, 183 participants completed the trial, with similar clinical characteristics at baseline reported in both groups. Baseline SU levels were 8.72 in the LDBen cohort and 8.59 in the LDFeb group. A higher percentage of patients in the LDBen cohort achieved the serum urate target when compared with the LDFeb cohort (61% vs 32%, P<0.001). Gout flares, urolithiasis, and other adverse events were similar among both LDBen and LDFeb groups (60% vs 65%, respectively), excluding transaminase elevation in the LDFeb cohort (LDBen 4% vsLDFeb 15%, P=0.008).

The single center, open-label study design, coupled with the short treatment period, limited the study and did not allow for long-term safety assessment. Results may not be generalizable to patients with higher SU levels or impaired kidney function, as investigators only included male patients with a baseline SU level ranging between 8 mg/dL and 10 mg/dL, and most patients were relatively young with few comorbidities. Additionally, since the availability of benzbromarone varies globally and is limited in many countries, the opportunity to implement this treatment strategy is limited. Finally, investigators did not compare the efficacy of benzbromarone and febuxostat in patients with normal excretion.

“Further investigation would be warranted to test precision in the model for use of a URAT1 inhibitor in selecting first line ULT according to primary renal uric acid underexcretion, as opposed to decreased renal function,” investigators concluded. “However, 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 (CKD).”

Reference:

Yan, F., Xue, X., Lu, J., et all. 2022. Superiority of low-dose benzbromarone to low-dose febuxostat in a prospective, randomized comparative effectiveness trial in gout patients with renal uric acid underexcretion. [online] Arthritis & Rheumatology. Available at: <https://onlinelibrary.wiley.com/doi/10.1002/art.42266>