This study aims to evaluate and compare the safety and efficacy of a low-dose titration strategy for febuxostat, starting at either 10 mg/day or 20 mg/day, in patients with primary gout.

We conducted a prospective, randomized, controlled trial involving 120 male participants diagnosed with acute gout, who met the 2015 ACR/EULAR classification criteria. Participants were divided into two groups: Group A started with 10 mg daily, increasing by 10 mg every two weeks (n=60), while Group B began with 20 mg daily, escalating by 20 mg biweekly (n=60). Uric acid-lowering therapy was initiated two weeks after the acute flare subsided, with follow-up lasting 24 weeks. Dosages were adjusted based on serum uric acid (SUA) levels and liver and kidney function, with a maximum dose of 80 mg/day. Target SUA levels were <360 μmol/L for patients without tophi or renal impairment, and 200-300 μmol/L for those with tophi or renal issues. During acute episodes, the current dosage was maintained, and NSAIDs were utilized for symptom relief. The primary outcome measured was the frequency of gout attacks over a 24-week period, while secondary outcomes included SUA target achievement rates, changes in liver and kidney function, and the occurrence of adverse events.

(1) Over 24 weeks, Group A experienced significantly fewer gout attacks compared to Group B (30.0% vs. 53.3%, P=0.010). The attack-free rate was 70.0% in Group A versus 46.7% in Group B. (2) In the subgroup without tophi, Group B had a higher SUA target achievement rate at week 4 (22.9% vs. 6.1%, P=0.019) and week 8 (69.6% vs. 47.9%, P=0.033), although this difference diminished by weeks 12-24 (P>0.05). No significant differences were observed among patients with tophi. (3) The rate of liver function abnormalities was significantly higher in Group B than in Group A (46.7% vs. 26.7%, P=0.042), with no serious adverse events reported in either group. 

Starting titration at 10 mg/day significantly lowers the risk of gout flare, particularly in the initial treatment phase, compared to starting at 20 mg/day. SUA control at 24 weeks is comparable, but there is a reduced risk of liver dysfunction. This ultra-low-dose initiation strategy may provide a safer and more tailored option for patients wary of acute flare or liver damage.