Background: The relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues.
Methods: Participants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events.
Results: This study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events.
Conclusions: Allopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.).