Efficacy and Safety of Ultra-Low Starting Dose Febuxostat Titration in Male Patients With Primary Gout.

Abstract

BACKGROUND: Since gout is a common metabolic arthritis caused by urate crystal deposition, urate-lowering therapy (ULT) is clearly indicated, but the initiation of ULT frequently causes paradoxical acute flares that in turn impair patient adherence. OBJECTIVE: This study sought to assess the effectiveness and safety of an ultra-low-dose initiation strategy for febuxostat (10&#x2009;mg/day) compared to the standard starting dose (20&#x2009;mg/day) in reducing initiation-related flares while maintaining long-term urate control. METHODS: 120 male patients with primary gout presenting with acute arthritis were randomly assigned to initiate febuxostat at 10&#x2009;mg/day (Group A) or 20&#x2009;mg/day (Group B), with protocol-mandated biweekly titration. The primary outcomes were gout flare frequency over 24&#x2009;weeks (assessed using Poisson regression), serum uric acid (SUA) target attainment, and the incidence of adverse events. RESULTS: Although both groups achieved comparable target SUA levels by week 24, Group A demonstrated a significantly lower overall flare incidence (36.7% vs. 70.0%; p&#x2009;<&#x2009;0.001), along with a greater percentage of flare-free patients (70.0% vs. 46.7%; p&#x2009;=&#x2009;0.016). Multivariable Poisson regression revealed that Group B had an approximately twofold higher risk of flares compared to Group A (Incidence Rate Ratio&#x2009;=&#x2009;1.95; p&#x2009;=&#x2009;0.012), with obese patients deriving the most pronounced benefit from the ultra-low-dose approach. To avert one additional flare, the calculated number needed to treat was 4.3. Additionally, the occurrence of clinically significant liver injury (ALT/AST >&#x2009;3&#xd7; ULN) was low in both groups, with 3.3% in Group A and 1.7% in Group B. Multivariable regression analysis confirmed that LDL-C is an independent predictor of ALT (&#x3b2;&#x2009;=&#x2009;12.90, p&#x2009;=&#x2009;0.009), while febuxostat dosage was not linked to hepatotoxicity. CONCLUSION: Initiating febuxostat at a dose of 10&#x2009;mg/day with gradual titration demonstrates a superior safety profile by effectively reducing early acute flares without compromising long-term urate control, which is particularly advantageous for high-risk cohorts, including obese patients.