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

Introduction A 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.  Methods Electronic 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). Results Four 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). Conclusion Dotinurad 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.