Response to Allopurinol and Febuxostat According to the Fractional Excretion of Urate in Men With Gout.

OBJECTIVE

Body mass index (BMI), glomerular filtration rate (GFR), and pretreatment urate levels have been reported to influence the urate-lowering response to allopurinol. We investigated whether the fractional excretion of uric acid (FEUA) also modulates this response and relates to oxypurinol concentrations. We further evaluated its potential influence on febuxostat, not as a direct comparison, but to determine whether the effect of FEUA was specific to allopurinol.

METHODS

The data are from n = 1,547 and n = 296 patients starting allopurinol and febuxostat, respectively. The relationship between FEUA (≤5.5% or >5.5%) and the dose response to allopurinol or febuxostat was assessed by linear mixed-effects regression models on serum urate levels and adjusted for BMI, estimated GFR (eGFR), and treatment doses. Concentrations of oxypurinol were measured in a subgroup of patients (n = 181). A multiple linear regression model was used to assess the association between FEUA and oxypurinol concentrations, adjusted for BMI, eGFR, allopurinol dosage, and serum urate levels.

RESULTS

The median FEUA in the whole population was 4.0% (quartile 1-3: 3%-5.1%). The changes in serum urate levels for each 150-mg increase in allopurinol in patients with FEUA ≤5.5% or >5.5% were -72.37 (confidence interval [CI] -74.81 to -69.94) μM and -65.96 (CI -71.29 to -60.62) μM, respectively (P = 0.032). We found higher oxypurinol concentrations in patients with the lowest FEUA (P = 0.032). However, we did not observe any interaction between the febuxostat response and FEUA (P = 0.13).

CONCLUSION

Allopurinol is more effective in patients with low FEUA, probably because of the reduced renal excretion of oxypurinol. These data highlight the similarity between the renal handling of oxypurinol and urate.