Rapid and regular dose escalation in urate lowering therapy: a pragmatic clinical trial

OBJECTIVES: Current guidelines for gout management do not clearly describe how to practically implement dose up-titration strategies to achieve optimal disease control. This study aimed to evaluate the risks and benefits of rapid versus regular dose escalation strategies for urate-lowering therapy (ULT) in real-world clinical practice. METHOD: This was a single-center pragmatic clinical trial based on real-world clinical data. Patients diagnosed with gout who required ULT were included, whereas those who declined ULT or had received prior ULT were excluded. Patients with gout were prescribed ULT in accordance with routine clinical practice, except that they were instructed to escalate their ULT dosage either within 2 weeks after treatment initiation (rapid group) or within 4 weeks after treatment initiation (regular group). The primary outcome was the post-escalation flare rate. Secondary outcomes included the serum uric acid target achievement rate and the time required to achieve the target. RESULTS: A total of 172 patients were enrolled, including 87 (50.6%) in the rapid group and 85 (49.4%) in the regular group. The post-escalation flare rate was higher in the rapid group than in the regular group (37.9% vs. 23.5%, P = 0.041); however, the difference was not statistically significant after multivariate adjustment (odds ratio = 0.91, 95% CI 0.33-2.48). The serum uric acid target achievement rates were similar between the two groups (60.9% vs. 62.4%, P = 0.847). However, the rapid group achieved the target significantly faster than the regular group (median 4.93 vs. 6.43 months, P = 0.020) and demonstrated a higher likelihood of target attainment (adjusted hazard ratio = 1.55, 95% CI 1.04-2.31; P = 0.033). CONCLUSIONS: Both rapid and regular dose escalation strategies effectively achieved serum uric acid targets in real-world clinical practice. Clinicians and patients should jointly determine an individualized urate-lowering protocol after carefully discussing the risks and benefits of each strategy. Key Points • This pragmatic clinical trial provides real-world evidence that both rapid and regular dose escalation strategies effectively achieve serum uric acid targets. • Rapid dose escalation significantly shortened the time required to achieve target serum uric acid levels but was associated with a higher unadjusted post-escalation flare rate, whereas regular escalation demonstrated a more favorable flare profile. • The choice between these strategies reflects a balance between treat-to-target and treat-to-symptom approaches, supporting individualized decision-making based on patient risk factors and preferences.