Two Milligrams of Dotinurad Beat Standard Febuxostat in Real-World Chinese Gout Patients

A new real-world study from China reports that the recently launched urate-lowering drug dotinurad outperformed the standard starting dose of febuxostat in the first four weeks of treatment, achieving markedly higher rates of serum uric acid control in patients with gout. In a single-center retrospective analysis of 70 adults treated at The Affiliated Guangdong Second Provincial General Hospital of Jinan University, 60.0 percent of patients taking 2 mg of dotinurad once daily reached the conventional treatment target of serum uric acid at or below 360 μmol/L after four weeks, compared with 45.7 percent of those taking 40 mg of febuxostat once daily. At the stricter target of 300 μmol/L, used for patients with tophi, the gap widened dramatically: 45.7 percent versus 14.3 percent. The findings, published in Drugs – Real World Outcomes, offer some of the first independent practice-based evidence on dotinurad since its Chinese launch in July 2025.

The study matters because gout has become a substantial and growing burden. The authors note that gout is the most common form of inflammatory arthritis among adults worldwide, with prevalence rising sharply since 1990 and an estimated 55.8 million people currently affected, a trend evident in China and internationally that may be linked to increases in population life expectancy. Sustained elevation of serum urate, generally defined as a concentration exceeding roughly 7 mg/dL, drives the deposition of monosodium urate crystals that trigger inflammatory arthritis. Hyperuricemia is also closely tied to chronic kidney disease and is thought to contribute to its progression in patients with gout, which is why urate-lowering therapy sits at the center of long-term gout management.

The existing drug arsenal carries well-documented limitations that shaped the rationale for the comparison. Febuxostat and allopurinol inhibit uric acid synthesis, with febuxostat associated in prior work with an increased risk of cardiovascular events, requiring caution in patients with cardiovascular disease and monitoring of cardiac enzymes, as well as possible liver dysfunction. Allopurinol, in Han Chinese patients, carries a higher risk of severe cutaneous adverse reactions, making HLA-B*5801 allele screening mandatory before initiation and the drug contraindicated in carriers. Benzbromarone, a uricosuric agent, raises hepatotoxicity concerns, has been linked to severe hepatitis and other liver injuries, and may promote renal accumulation of uremic toxins by inhibiting the ABCG2 transporter while also blocking intestinal uric acid excretion.

Dotinurad works differently. It is a novel selective uric acid reabsorption inhibitor that promotes uric acid excretion by selectively blocking urate transporter 1, or URAT1, the molecule responsible for reabsorbing uric acid in the renal proximal tubules. Crucially, it does not inhibit ABCG2, the intestinal transporter that exports uric acid and indoxyl sulfate, a uremic toxin implicated in chronic kidney disease progression. Approved in Japan in 2020 for hyperuricemia and gout, dotinurad had, until recently, been studied almost exclusively in Japanese populations. In December 2025, a randomized, multicenter, double-blind Phase III trial in China reported that 2 mg of dotinurat once daily was noninferior to 40 mg of febuxostat for uric acid target attainment at week 12, and that 4 mg daily was significantly superior at week 24, with no new safety signals.

Because randomized trials enroll highly selected patients under standardized protocols and intensive follow-up, the research team set out to capture how dotinurad performs in ordinary clinical practice during its first year on the Chinese market. Their study enrolled 70 consecutive eligible inpatients and outpatients from the Department of Rheumatology and Immunology between 1 January and 30 December 2025, all meeting the 2015 ACR/EULAR gout classification criteria. Exclusion criteria removed secondary hyperuricemia, treatment durations under four weeks, missing laboratory data, severe hepatic or renal dysfunction, psychiatric disorders, malignancies, other urate-lowering agents, and loss to follow-up. Treating clinicians chose the drug at their own discretion based on individualized clinical judgment and patient preference, with 35 patients assigned to each arm. Because dotinurad only launched on 1 July 2025, its users were enrolled from July through December, while febuxostat patients were enrolled across the full year, a design asymmetry the authors acknowledged.

The primary outcome was the proportion of patients reaching serum urate targets after four weeks of continuous medication, with secondary outcomes covering the week-4 urate level and the mean change from baseline. Laboratory parameters, including serum uric acid, alanine aminotransferase, aspartate aminotransferase, serum creatinine, and estimated glomerular filtration rate, were measured at baseline and at one month. Statistical analysis used SPSS version 25.0, with analysis of covariance adjusting for baseline confounders: presence of tophi, comorbidities, age, gout duration, baseline serum uric acid, baseline creatinine, baseline ALT and AST, and eGFR, with Bonferroni-corrected P values. At baseline, the groups did not differ significantly in age, sex, or comorbidities, but disease duration, presence of tophi, and eGFR did differ significantly, making the adjusted analysis essential.

The effectiveness results were striking. Baseline uric acid levels were statistically similar between groups (P = 0.227), yet after four weeks the adjusted serum uric acid levels were 294.47 ± 19.31 μmol/L in the dotinurad group versus 380.85 ± 21.43 μmol/L in the febuxostat group, a significant difference (P = 0.003). Both drugs produced significant within-group urate reductions from baseline (P < 0.001 in each), but the adjusted change from baseline in uric acid also favored dotinurad significantly (P = 0.003). The authors report that these findings align with the domestic Phase III trial and with a Japanese Phase III study showing that dotinurad reduced serum uric acid as early as two weeks after treatment initiation.

The safety picture diverged in ways the authors link to mechanism. Within the febuxostat group, serum creatinine and AST rose significantly from baseline over the four weeks (P = 0.011 and P = 0.030, respectively), while ALT did not change significantly. In the dotinurad group, no statistically significant changes appeared in ALT, AST, or creatinine. After covariate adjustment, significant intergroup differences emerged in the baseline-to-week-4 changes in uric acid and creatinine (P = 0.003 and P = 0.029), but not in ALT or AST (P = 0.761 and P = 0.551). The authors propose that febuxostat’s potent inhibition of ABCG2 may reduce intestinal uric acid excretion and disrupt indoxyl sulfate transport, offering one potential explanation for the creatinine elevation, and they cite a 2019 post-marketing study reporting that febuxostat-related acute renal failure was reported 5.7-fold more frequently than with other medications. Dotinurad, by sparing ABCG2, preserves indoxyl sulfate excretion. The authors also note that prior studies reporting renal benefits of dotinurad evaluated patients after at least three months, longer than this study’s four-week window, and no renal improvement trend was detected in the dotinurad group here.

The conclusions come wrapped in careful caveats. The authors state explicitly that their findings apply only to the clinical setting where febuxostat is initiated at 40 mg in Chinese patients, and cannot be extrapolated to the 80 mg starting dose used in the landmark Western APEX and FACT trials, which Chinese practice avoids for ethnic and regional reasons and to minimize risks of severe adverse reactions such as DRESS. Adverse events were extracted retrospectively from medical records and patient-reported symptoms rather than collected prospectively, and only clinically significant laboratory abnormalities were counted. The study’s limitations include its single-center retrospective design, potential selection bias, the absence of propensity score matching due to limited sample size, non-synchronized enrollment windows, treatment assignment by clinical judgment rather than randomization, a small sample, and an all-male cohort reflecting the natural demographic distribution of presenting patients rather than deliberate exclusion. Follow-up of only four weeks provides preliminary short-term evidence that cannot speak to long-term efficacy, durability, or delayed adverse events. Within those boundaries, the authors conclude that 2 mg daily dotinurad delivered superior short-term urate-lowering effectiveness and favorable hepatic and renal tolerability, evidence they suggest may help clinicians individualize therapy for patients who need rapid urate control.

Subject of Research: A retrospective real-world comparison of dotinurad and febuxostat for short-term urate-lowering effectiveness and safety in Chinese patients with gout.

Article Title: Real-World Effectiveness and Safety of Dotinurad in Chinese Patients with Gout: A Comparative Analysis

Article References: Yi, G., Huang, X., Huang, Y., Huang, Z., Zheng, S., Huang, Z., Deng, W., Zheng, C., & Li, T. (2026). Real-World Effectiveness and Safety of Dotinurad in Chinese Patients with Gout: A Comparative Analysis. Drugs – Real World Outcomes, 13(3), 465-473. https://doi.org/10.1007/s40801-026-00574-6

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00574-6

Keywords: gout, dotinurad, febuxostat, hyperuricemia, urate-lowering therapy, URAT1 inhibitor, serum uric acid, real-world study, kidney function, retrospective cohort, China, drug safety