Gout Patients on Ruzinurad Were More Likely to Achieve Target Serum Uric Acid Level

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A phase 2 study revealed combining febuxostat with the inhibitor ruzinurad demonstrated a superior serum uric acid lowering effect compared to placebo plus febuxostat in patients with primary gout and hyperuricemia. The data was presented in a poster presentation at the 2024 European Alliance of Associations for Rheumatology (EULAR) from June 12 – June 15 in Vienna, Austria.¹

High levels of uric acid, considered > 7 mg/dL for men and > 6 mg/dL for women, are the biggest risk factor for gout, according to the Arthritis Foundation.² Many patients with gout do not achieve or maintain the target serum uric acid level with the use of xanthine oxidate inhibitors, such as febuxostat.¹ Research suggests adding a uricosuric agent can help improve a patient’s treatment response.

Ruzinurad (SHR4640), a highly selective and potent inhibitor against uric acid transporter 1 (URAT1), is effective at lowering the serum uric acid level in patients with hyperuricemia, as shown in earlier clinical trials. Phase 1 data showed the combination of ruzinurad and febuxostat provided a synergistic effect in reducing serum uric acid levels and was well-tolerated.

Investigators from China sought to assess the efficacy and safety of febuxostat plus ruzinurad in treating primary gout and hyperuricemia. They conducted a 12-week, multicenter, randomized, double-blind, placebo-controlled phase 2 study, aiming to evaluate the primary endpoint of the proportion of patients achieving serum uric acid level of ≤ 360 μmol/L at Week 12.

Participants had gout with a fasting serum uric acid level of ≥ 3Bas90 µmol/L and were on a stable dose of febuxostat (40, 60, 80 mg/day) for ≥ 6 weeks. The team randomized 151 patients 1:1 to receive oral ruzinurad 10 mg, ruzinurad 5 mg, or placebo, stratified by the febuxostat dose at screening. Patients started ruzinurad at a low dose of 1 mg/day which gradually increased; the febuxostat oral dose stayed the same from screening.

Baseline characteristics were similar across the groups ruzinurad 10 mg, ruzinurad 5 mg, and placebo for sex (male: 96.1%, 95.9%, 98%, respectively), mean age (34.6, 37.5, 38.5 years, respectively), mean serum uric acid (514.1, 514.0, 504.8 μmol/L, respectively), eGFR (<90 mL/min: 37.3%, 36.7%, 35.3%, respectively), and tophi (74.5%, 67.3%, 72.5%, respectively).

At week 12, a significantly greater proportion of patients in the ruzinurad groups achieved the target serum uric acid level of ≤ 360 μmol/L with 56.9% in the 10 mg group (odds ratio [OR], 8.7; 95% confidence interval [CI], 3.3 – 23.2; P < .0001) and 53.1% in the 5 mg group (95% CI, 2.7–18.9; P < .0001) compared to the placebo group.

Subgroup analyses based on baseline eGFR, serum uric acid, and tophus showed superior effects of ruzinurad over placebo.

Furthermore, proportions of patients achieving a serum uric acid level of ≤ 300 μmol/L at Week 12 were also greater in the ruzinurad groups with 43.1% in the 10 mg group (OR, 7.2; 95% CI, 2.4 – 21.2; P = .001) and 38.8% in the 5 mg group (95% CI, 1.9 –17.2; P = .0009) versus placebo group.

Additionally, treatment-emergent adverse events (TEAEs) occurred in 74.5% of patients taking ruzinurad 10 mg, 87.8% taking ruzinurad 5 mg, and 80.4% taking placebo. The most common TEAEs were gout flares (39.2%, 49%, and 45.1%, respectively). Most TEAEs were mild to moderate, and none led to treatment discontinuation or death.

“Addition of the URAT1 inhibitor ruzinurad (both 10 and 5 mg) to febuxostat demonstrated superior sUA lowering effect versus placebo plus febuxostat and was generally well-tolerated in patients with primary gout and hyperuricemia uncontrolled on febuxostat alone,” investigators concluded.

References

1. ^{Bao, C, Ding, H, Hu, D. OP0129 A 12-Week, Multicenter, Randomized, 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. Abstract presented at 2024 European Alliance of Associations for Rheumatology (EULAR) in Vienna, Austria from June 12 – June 15, 2024.}
2. ^{Rath, L. High & Low Uric Acid Symptoms: How to Stay in a Safe Range. Arthritis Foundation. December 12, 2022. https://www.arthritis.org/diseases/more-about/high-low-uric-acid-symptoms-how-stay-in-safe-range. Accessed June 25, 2024.}