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

• Published in: Clinical and experimental hypertension (1993) 2021-11, Vol.43 (8), p.730-741
• Main Authors: Takahashi, Toshinari, Beppu, Takanobu, Hidaka, Yuji, Hosoya, Tatsuo
• Format: Article
• Language: English
• Subjects: Benzothiazoles; Clinical Trials, Phase II as Topic; dotinurad; gout; Gout - complications; Gout - drug therapy; Gout Suppressants - therapeutic use; Humans; hypertension; Hypertension - complications; Hypertension - drug therapy; Hyperuricemia; Hyperuricemia - complications; Hyperuricemia - drug therapy; Pharmaceutical Preparations; selective urate reabsorption inhibitor; URAT1 inhibitor; Uric Acid; Uricosuric Agents - therapeutic use
• ISSN: 1064-1963; 1525-6006; 1525-6006
• DOI: 10.1080/10641963.2021.1950752

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.