Objectives: To investigate the efficacy and tolerability of allopurinol as first-choice antihyperuricemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment.
Methods: Prospective, multi-centre, open-label, randomised controlled trial of gout patients with normal renal function. Patients were given 300 mg allopurinol for 2 months (stage 1). When allopurinol was not tolerated or failed to attain target serum urate concentrations (sUr) ≤0.30 mmol/L (5.0 mg/dl), which was defined as successful, patients were randomised to benzbromarone 200 mg/day or probenecid 2000 mg/day and treated for 2 months (stage 2).
Results: Ninety-six patients were enrolled in stage 1. Eighty-two patients (85%) were eligible for the analysis of stage 1: sUr concentrations decreased 36[±11]% (mean[±SD]) from baseline; twenty patients (24%) attained target sUr ≤0.30 mmol/l; nine patients (11%) stopped allopurinol because of adverse drug reactions. Sixty-two patients were enrolled in stage 2: 27 patients received benzbromarone (3 lost to follow-up) and 35 received probenecid (4 lost to follow-up). With benzbromarone 22 out of 24 patients (92%) were treated successfully. Treatment success with probenecid was 20 out of 31 patients (65%) (p=0.03 compared with benzbromarone). Compared with baseline values, sUr decreased 64[±9]% applying benzbromarone and decreased 50[±7]% applying probenecid (p<0.001).
Conclusion: This study demonstrates a poor efficacy and tolerability profile of allopurinol 300 mg/day to attain a biochemical predefined target level of sUr ≤0.30 mmol/l after 2-months treatment. In stage 2, benzbromarone 200 mg/day is more effective and better tolerated than probenecid 2000 mg/day (controlled-trials.com number ISRCTN21473387).