Uric acid-lowering effect of dotinurad, a novel selective urate reabsorption inhibitor, in hypertensive patients with gout or asymptomatic hyperuricemia: a pooled analysis of individual participant data in phase II and III trials

Background: Hyperuricemia is a risk factor for the development of hypertension and is comorbid in many hypertensive patients. According to Japanese hypertension management guidelines published in 2019, a target serum uric acid level of <= 6.0 mg/dL is recommended in hypertensive patients with gout or asymptomatic hyperuricemia. Dotinurad is a novel uric acid-lowering drug classified as a selective urate reabsorption inhibitor. A pooled analysis was performed on the uric acid-lowering effect of dotinurad in 222 hypertensive patients with gout or asymptomatic hyperuricemia in four clinical trials (NCT02344862, NCT02416167, NCT03100318, NCT03372200). Moreover, we analyzed the long-term uric acid-lowering effect of dotinurad in 154 hypertensive patients with gout or asymptomatic hyperuricemia (NCT03006445). Results: In the pooled analysis, the percent change in the decrease of serum uric acid with the use of dotinurad was 42.17 +/- 12.42% at a dose of 2 mg and 60.42 +/- 8.03% at a dose of 4 mg; the percentage of patients who achieved a serum uric acid level of <= 6.0 mg/dL was 82.8% and 100.0%. The long-term uric acid-lowering effect of dotinurad showed almost the same results. In this study, the concomitant use of diuretics or angiotensin II receptor blockers affected the uric acid-lowering effect of dotinurad at only a dose of 2 mg in the pooled analysis. Conclusions: In the pooled analysis, dotinurad lowered serum uric acid levels. Dotinurad has an achievement rate of over 80% for serum uric acid level of <= 6.0 mg/dL in both analyses, and will be clinically useful for the management of hyperuricemic states in hypertensive patients.

Automated summary

Dotinurad effectively lowers serum uric acid levels in hypertensive patients with gout or asymptomatic hyperuricemia, especially at a dose of 4 mg, with consistent long-term results. The drug has a high achievement rate of over 80% in reaching the target serum uric acid level of <= 6.0 mg/dL in both short-term and long-term analyses.