Efficacy and tolerability of urate-lowering drugs in gout: a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised controlled trial in gout patients with normal renal function. Enrolled patients were given 300 mg allopurinol for 2 months (stage 1). Those patients who could not tolerate allopurinol or who did not attain the target serum urate concentration (sUr) <= 0.30 mmol/l (5.0 mg/dl), which was defined as successful, were randomised to benzbromarone 200 mg/day or probenecid 2 g/day for another 2 months (stage 2). Results: 96 patients were enrolled in stage 1.82 patients (85%) were eligible for the analysis at the end of stage 1: there was a mean (SD) decrease in sUr concentration of 35 (11)% from baseline; 20 patients (24%) attained target sUr <= 0.30 mmol/l; and 9 patients (11%) stopped allopurinol because of adverse drug reactions. 62 patients were enrolled in stage 2. 27 patients received benzbromarone (3 patients not eligible for analysis) and 35 received probenecid (4 patients not eligible for analysis). Treatment with benzbromarone was successful in 22/24 patients (92%) and with probenecid in 20/31 patients (65%) (p = 0.03 compared with benzbromarone). Compared with baseline values, there was a mean (SD) decrease of sUr concentration of 64 (9)% with benzbromarone and 50 (7)% with probenecid (p < 0.001). Conclusion: This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr <= 0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day. Trial registration number: ISRCTN21473387.