More patients hit their uric acid target with febuxostat and ruzinurad combination

Adding the uricosuric ruzinurad to febuxostat led to a significant proportion of patients reaching their serum uric acid (sUA) goal of ≤360 µmol/L. On a higher dose, 56.9% of patients successfully achieved this sUA level, and 43.1% hit the threshold of ≤300 µmol/L.

“Despite the use of xanthine oxidase inhibitors, a large proportion of patients with gout still fail to achieve or maintain the target sUA level. Adding uricosuric agents to an xanthine oxidase inhibitor represents an attractive therapeutic strategy for inadequate responders,” Dr Huihua Ding (Shanghai Jiao Tong University, China) explained the background of the trial [1]. She presented a 12-week phase 2 study (NCT05513976) that investigated ruzinurad as an add-on medication for patients with primary gout and hyperuricemia, who failed to meet their target sUA level on febuxostat alone. In 3 study groups, participants received febuxostat plus placebo or ruzinurad that was up-titrated to 5 mg or 10 mg daily.

The 151 randomised participants had a mean age between 34.6 and 38.5 years, and over 95% were men. The mean sUA ranged from 504.8 to 514.1 µmol/L. More than 96% of the participants were on a 40 mg dose of febuxostat and around two-thirds had an eGFR ≥90 mL/min.

At week 12, 56.9% in the 10 mg (OR 8.7; 95% CI 3.3–23.3) and 53.1% in the 5 mg group (OR 7.1; 95% CI 2.7–18.9) attained the primary endpoint of a sUA ≤360 µmol/L in contrast to 13.7% on placebo (P<0.001 for both comparisons; see Figure). This translated into sUA differences of -37.7% (10 mg), -30.1% (5 mg), and -8.7% (placebo). sUA ≤300 µmol/L was achieved in 43.1% (P<0.001) and 38.8% (P<0.001) versus 9.8% of the participants, respectively. As most adverse events were mild-to-moderate, Dr Ding deemed ruzinurad generally well-tolerated with a manageable safety profile.

Figure: Proportion of patients achieving sUA target following 12 weeks of treatment [1]



sUA, serum uric acid.

“The present study met its primary objective, i.e. superiority of ruzinurad plus febuxostat over placebo plus febuxostat in the achievement rate of sUA ≤360 µmol/L in patients with primary gout and hyperuricemia uncontrolled on febuxostat alone,” Dr Ding summarised. These findings are likely important going forward as the management of gout by rheumatologists often starts with difficult-to-treat cases referred from primary care, where xanthine oxidase inhibitiors have not adequately worked.

1. Ding H. 12-week, multicentre, randomised, double-blind, placebo-controlled, phase 2 study of ruzinurad (SHR4640) in combination with febuxostat for primary gout and hyperuricemia with an inadequate response to febuxostat alone. OP0129, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 202429 July 2024