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

Takahashi, Toshinari; Beppu, Takanobu; Hidaka, Yoshiki; Hosoya, Tatsuo

doi:10.1080/10641963.2021.1950752

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…These suggest that selective inhibition of URAT1 is a reasonable therapy to reduce effectively the SUA levels in such patient populations with renal urate underexcretion [ 19 ]. Therefore, we sought to assess the effects of dotinurad therapy primarily on the SUA levels in patients with hyperuricemia complicated with hypertension and found that the therapy substantially reduced the SUA levels over 24 weeks, as observed in previous phase 2 and 3 clinical studies with dotinurad in general patient populations with hyperuricemia [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Clinical effects of a selective urate reabsorption inhibitor dotinurad in patients with hyperuricemia and treated hypertension: a multicenter, prospective, exploratory study (DIANA)

Tanaka

Hisauchi

et al. 2023

Eur J Med Res

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Introduction Dotinurad is a newer urate-lowering agent that selectively inhibits urate transporter 1 in the renal proximal tubule and increases urinary urate excretion. Currently, little is known about the clinical efficacies of dotinurad in patients with hyperuricemia and hypertension. The aim of this study was to assess the clinical effects of a selective urate reabsorption inhibitor dotinurad on serum uric acid (SUA) levels and relevant vascular markers in patients with hyperuricemia and treated hypertension. Methods This investigator-initiated, multicenter, prospective, single-arm, open-label, exploratory clinical trial in Japan enrolled patients with hyperuricemia and treated hypertension who received a 24-week dotinurad therapy (a starting dose at 0.5 mg once daily and up-titrated to 2 mg once daily). The primary endpoint was a percentage change in the SUA level from baseline to week 24. The secondary endpoints were cardiovascular and metabolic measurements, including changes in the cardio-ankle vascular index (CAVI) and derivatives of reactive oxygen metabolites (d-ROMs) concentration at week 24. Results Fifty patients (mean age 70.5 ± 11.0 years, with 76.0% being men, and mean SUA level 8.5 ± 1.2 mg/dL) were included in the analysis. The percentage change from baseline in the SUA level at week 24 was − 35.8% (95% confidence interval [CI] − 39.7% to − 32.0%, P < 0.001), with approximately three quarters of patients achieving an SUA level of ≤ 6.0 mg/dL at week 24. The proportional changes from baseline in the geometric mean of CAVI and d-ROMs at week 24 were 0.96 (95% CI 0.92 to 1.00, P = 0.044) and 0.96 (95% CI 0.92 to 1.00, P = 0.044), respectively. Conclusion In addition to meaningful SUA-lowering effects, 24 weeks of dotinurad therapy may favorably affect arterial stiffness and oxidative stress markers, suggesting off-target vascular protection of dotinurad. Further research is expected to verify our findings and elucidate the entire off-target effects of dotinurad. Trial registration jRCTs021210013, registration date June 24, 2021

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Section: Discussionmentioning

confidence: 99%

Clinical effects of a selective urate reabsorption inhibitor dotinurad in patients with hyperuricemia and treated hypertension: a multicenter, prospective, exploratory study (DIANA)

Tanaka

Hisauchi

et al. 2023

Eur J Med Res

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“…In phase II and III trials, >80% of patients were able to achieve UA levels <6 mg/dL (356 μM). Renal adverse events, a concern first raised in trials of lesinurad, were not reported in the short‐term trials with dotinurad 109,110 . With any uricosuric, UA urolithiasis is always a risk.…”

Section: Inhibitors Of Ua Transportmentioning

confidence: 99%

“…Renal adverse events, a concern first raised in trials of lesinurad, were not reported in the short-term trials with dotinurad. 109,110 With any uricosuric, UA urolithiasis is always a risk. In longer follow-up at 34 weeks, the incidence of renal calculi was 1.5%.…”

Section: Selective Ua Reabsorption Inhibitorsmentioning

confidence: 99%

Uric acid transport, transporters, and their pharmacological targeting

Adomako

Moe

2023

Acta Physiologica

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Knowledge of uric acid (UA) crystallopathies preceded the identification of this compound. How the body handles and transports UA proved even more elusive. Over several decades, advances in molecular phenotyping have illuminated this hitherto nebulous field. Closely parallel to the characterization of the transport mechanisms of UA in the body was the development of drugs designed to manipulate UA levels. In this review, we highlight the study of UA transport and transporters. This is an evolving field, and we expect our knowledge of the transport mechanisms to both widen and deepen further. We focus on the best‐characterized transporters rather than an exhaustive catalog of all suspected transporters. We review the established and novel compounds that modulate UA transport.

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“…For that reason, we decided to summarize the newest insights. Table 1 [18][19][20][21][22][25][26][27][28][29][30] enlists research on new uricosuric agents [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: How To Treat the Gouty Patient?mentioning

confidence: 99%

What is the Place for Uricosuric Agents in Gout Management?

Siddiq

Jansen

Rasker

2022

CRR

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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

Abstract: 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, Clinical and Experimental Hypertension,

Cited by 7 publications

References 24 publications

Clinical effects of a selective urate reabsorption inhibitor dotinurad in patients with hyperuricemia and treated hypertension: a multicenter, prospective, exploratory study (DIANA)

Clinical effects of a selective urate reabsorption inhibitor dotinurad in patients with hyperuricemia and treated hypertension: a multicenter, prospective, exploratory study (DIANA)

Uric acid transport, transporters, and their pharmacological targeting

What is the Place for Uricosuric Agents in Gout Management?

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