A non-inferiority study of the novel selective urate reabsorption inhibitor dotinurad versus febuxostat in hyperuricemic patients with or without gout

Hosoya, Tatsuo; Furuno, Kazuki; Kanda, Shingo

doi:10.1007/s10157-020-01851-6

Cited by 18 publications

(19 citation statements)

References 17 publications

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“…After removing duplicates and screening titles and abstracts, 30 full-text articles were reviewed. Finally, four RCTs (684 patients) were eligible for inclusion in the study (Figure 1) [2,7,8,10]. All the included studies assessed the efficacy and safety of dotinurad in hyperuricemic patients with or without gout.…”

Section: Resultsmentioning

confidence: 99%

“…All the included studies assessed the efficacy and safety of dotinurad in hyperuricemic patients with or without gout. Two trials compared dotinurad with placebo, while the rest of the two used active control, i.e, benzbromarone and febuxostat as a comparator [2,7,8,10].…”

Section: Resultsmentioning

confidence: 99%

“…The risk of bias assessment for randomized controlled trials included in our study was summarized in Table 2. The risk of bias for random sequence generation was low for all studies, however, it was unclear for allocation concealment [2,7,8,10]. All trials were randomized, double-blind studies [2,7,8,10].…”

Section: Risk Of Biasmentioning

confidence: 99%

“…Hence, in light of the notably higher prevalence of under-excretion hyperuricemia than the overproduction type, there is a pressing need for safer and more effective uricosuric drugs for the treatment of underexcretion hyperuricemic patients [9]. Dotinurad, a novel selective urate reabsorption inhibitor (SURI), increases uric acid excretion by the kidneys by selectively inhibiting urate transporter 1 (URAT1), the protein responsible for the reabsorption of uric acid, in the proximal renal tubules [10]. No inhibitory effect is exerted on organic anion transporter (OAT) 1 and 3, and ABCG2, the transporters responsible for renal and intestinal uric acid secretion, respectively [10].…”

Section: Introductionmentioning

confidence: 99%

“…Dotinurad, a novel selective urate reabsorption inhibitor (SURI), increases uric acid excretion by the kidneys by selectively inhibiting urate transporter 1 (URAT1), the protein responsible for the reabsorption of uric acid, in the proximal renal tubules [10]. No inhibitory effect is exerted on organic anion transporter (OAT) 1 and 3, and ABCG2, the transporters responsible for renal and intestinal uric acid secretion, respectively [10]. However, no conclusive evidence on the efficacy and safety of dotinurad is available.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Dotinurad in Hyperuricemic Patients With or Without Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Iqbal¹,

Iqbal²,

Farid³

et al. 2021

Cureus

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IntroductionA systematic review and meta-analysis of the available randomized controlled trials (RCTs) were conducted to investigate the efficacy and safety of dotinurad in hyperuricemic patients with or without gout. Dotinurad is a novel selective urate reabsorption inhibitor (SURI) that increases uric acid excretion by selectively inhibiting urate transporter 1 (URAT1). To the best of our knowledge, this is the first meta-analysis conducted to gauge the efficacy and safety of dotinurad. MethodsElectronic databases (PubMed, the Cochrane Library, and ClinicalTrials.gov) were searched from inception till March 2, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Randomized controlled trials comparing the efficacy and safety of dotinurad with placebo-or active (febuxostat or benzbromarone) control were included. The eligible studies were analyzed with RevMan 5.3 Software (The Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen). ResultsFour eligible studies, consisting of 684 hyperuricemic patients were included. The number of patients who achieved serum uric acid (sUA) levels ≤ 6.0 mg/dl favoured dotinurad 1 mg group as compared to placebo group (risk ratio {RR} = 39.27, 95% onfidence interval {CI}, 5.59 to 275.65; p = 0.0002), dotinurad 2 mg group compared with placebo group (RR = 45.36, 95% CI, 6.48 to 317.38; p= 0.0001), and dotinurad 4 mg group compared with placebo group (RR = 54.16, 95% CI, 7.76 to 377.77; p < 0.0001). Conversely, there was no significant difference in the number of patients who achieved the target sUA levels between dotinurad 2 mg and active control (RR = 1.00, 95% CI, 0.92 to 1.08; p = 0.91). Moreover, the percentage change in sUA levels from baseline to final visit favoured dotinurad 1 mg vs. placebo ((RR = 36.51, 95% CI, 33.00 to 40.02; p < 0.00001), dotinurad 2 mg vs. placebo (RR = 46.70, 95% CI, 42.53 to 50.87; p < 0.00001), and dotinurad 4 mg vs. placebo (RR = 63.84, 95% CI, 60.51 to 67.16; p < 0.00001), while no significant difference was seen in dotinurad 2 mg vs. active control (RR = -0.08, 95% CI, -4.27 to 4.11; p= 0.97). Compared with active or placebo control, dotinurad 2 mg showed no significant difference in the number of events of gouty arthritis (RR= 1.31, 95% CI, 0.47 to 3.71; p = 0.60), the number patients with adverse events (RR = 1.09, 95% CI, 0.91 to 1.30; p = 0.36), and the number of patients who experienced adverse drug reactions (RR = 1.00, 95% CI, 0.68 to 1.47; p = 0.99). ConclusionDotinurad shows significant improvement in serum uric acid levels in hyperuricemic individuals with or without gout. Its urate-lowering effect is comparable to the commonly available anti-hyperuricemic agents. Moreover, it is effective at doses 1 mg, 2 mg, and 4 mg and well-tolerated at a dose of 2 mg.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Risk Of Biasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and Safety of Dotinurad in Hyperuricemic Patients With or Without Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Iqbal¹,

Iqbal²,

Farid³

et al. 2021

Cureus

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Changes in Urinary Uric Acid Concentration after Dotinurad Administration to Patients with Hyperuricemia: A Post Hoc Analysis of Two Clinical Trials in Japan

Takahashi

Sasaki²,

Shimizu

et al. 2023

Clinical Pharm in Drug Dev

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Dotinurad has been approved in Japan as a selective urate reabsorption inhibitor for the treatment of gout and hyperuricemia. The relationship between uric acid crystallization and the use of uricosuric drugs is widely acknowledged; however, the relationship between changes in urinary uric acid concentration and urine pH or volume has not been sufficiently analyzed. Therefore, we investigated the changes in urinary uric acid concentration following dotinurad administration as well as the relationship between urine pH or volume and urinary uric acid concentration. This post hoc analysis used data from 2 clinical trials that included 12 and 26 patients with hyperuricemia who received dotinurad treatment (for 7 days on an inpatient basis and 14 weeks on an outpatient basis, respectively). The urinary uric acid concentration transiently increased in the early stages of dotinurad use and when its dose was increased, but decreased over time. No uric acid concentrations exceeded the soluble limit at any urine pH. An inverse correlation was observed between urine volume and urinary uric acid concentration. This study highlights the significance of adequately managing urinary uric acid concentrations by increasing urine volume and alkalinizing urine to prevent uric acid crystallization during dotinurad administration.

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Comparative study of a novel selective urate reabsorption inhibitor “dotinurad” among patient groups with different stages of renal dysfunction

Takahashi

Beppu²,

Hidaka³

et al. 2021

Clin Exp Nephrol

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Background Dotinurad is a selective urate reabsorption inhibitor (SURI), which selectively inhibits URAT1 to lower serum uric acid levels in patients with hyperuricemia. Herein, the effects of dotinurad were compared among patient groups with different stages of renal dysfunction. Methods Patient data from four clinical trials were pooled and divided into four groups according to the stage of renal dysfunction to compare the effects of dotinurad at different stages. The grouping (stages G1–G3b) was based on the estimated glomerular filtration rate (eGFR) of the patients. In addition, patient data from a long-term study (34 or 58 weeks) were evaluated in the same manner. Results In the pooled analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 64.7–100.0% at a dose of 2 or 4 mg. In the long-term analysis, the percentage of patients achieving a serum uric acid level of ≤ 6.0 mg/dL was 60.0–100.0% at a dose of 2 or 4 mg. Although the outcomes in stage G3b were worse due to higher baseline serum uric acid levels, satisfactory outcomes were observed in all stages. Even in stages G3a and G3b, when renal function declined, the eGFR remained constant throughout the dose period. Conclusion The efficacy of dotinurad was confirmed in hyperuricemic patients with normal renal function (stage G1) and mild to moderate renal dysfunction (stage G2–G3b). Dotinurad was found to be effective in the treatment of hyperuricemia in patients with mild to moderate renal dysfunction.

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A non-inferiority study of the novel selective urate reabsorption inhibitor dotinurad versus febuxostat in hyperuricemic patients with or without gout

Cited by 18 publications

References 17 publications

Efficacy and Safety of Dotinurad in Hyperuricemic Patients With or Without Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Efficacy and Safety of Dotinurad in Hyperuricemic Patients With or Without Gout: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Changes in Urinary Uric Acid Concentration after Dotinurad Administration to Patients with Hyperuricemia: A Post Hoc Analysis of Two Clinical Trials in Japan

Comparative study of a novel selective urate reabsorption inhibitor “dotinurad” among patient groups with different stages of renal dysfunction

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