Usefulness of concomitant administration of dotinurad 0.5 mg in patients who cannot achieve therapeutic-targeted serum uric acid levels with febuxostat 40 mg

Abstract

For male patients with hyperuricemia and gout who were unable to achieve a serum uric acid level of 6.0 mg or less with febuxostat 40 mg, we compared the serum uric acid level reduction rate and treatment goal achievement rate of a serum uric acid level 6.0 mg/dL or less between 40 patients who received an additional dose of febuxostat 20 mg and 23 who received dotinurad 0.5 mg in combination. In the febuxostat 20 mg addition group, serum uric acid levels significantly decreased from 6.6 ± 0.6 mg/dL to 5.3 ± 0.7 mg/dL, with a reduction rate of 19.8 ± 9.7%, and an achievement rate of 90.0%. On the other hand, in the dotinurad 0.5 mg combination group, the serum uric acid level decreased from 6.9 ± 0.6 mg/dL to 5.4 ± 0.8 mg/dL, with a reduction rate of 21.2 ± 13.8%, and an achievement rate of 78.3%, with no significant difference in treatment effects between the two groups. In the 6 patients who did not achieve the therapeutic target values with febuxostat 60 mg, when febuxostat was reduced to 40 mg and dotinurad 0.5 mg was co-administered, the serum uric acid level decreased significantly from 6.4 ± 0.3 mg/dL to 5.2 ± 0.7 mg/dL, with a reduction rate of 19.6 ± 10.8%, and an achievement rate of 100%. The therapeutic effects of febuxostat 20 mg added to febuxostat 40 mg and combined with dotinurad 0.5 mg were not affected by the type of hyperuricemia. When administered alone, febuxostat 10 mg reduced the serum uric acid level by approximately 20%, equivalent to dotinurad 0.5 mg; however, when administered in addition to 40 mg of febuxostat, twice the dose of 20 mg would have been required to achieve the same effect as 0.5 mg of dotinurad. Comparing the rates of reduction in serum uric acid levels in the febuxostat 20 mg and 40 mg groups with the febuxostat 10 mg group, the dose increased by 2 and 4 times respectively, but the rate of decrease in serum uric acid levels remained at a 1.4 and 1.8 times increase, suggesting that the attenuation in the rate of decrease in serum uric acid levels when febuxostat 20 mg was added to febuxostat 40 mg was a phenomenon associated with increasing the dose of the same drug. The combined administration of 40 mg of febuxostat and 0.5 mg of dotinurad, which has a different uric acid lowering mechanism, was considered to be a useful method for the treatment of hyperuricemia and gout.