Achieving serum urate targets within 1 year of treatment initiation may significantly reduce major cardiovascular events in patients with gout, according to new research presented at the 2025 EULAR congress in Barcelona.
Past EULAR recommendations advised maintaining serum urate levels <6 mg/dL (360 μmol/L) and <5 mg/dL (300 μmol/L) in patients with severe gout. Despite available treatments, gout continues to be underdiagnosed, and its management remains suboptimal. A meta-analysis of English and Swedish primary care data linked to hospitalization and mortality records evaluated outcomes in more than 116,000 patients with gout, 16,201 of whom experienced a major adverse cardiovascular event (MACE) during follow-up.
Patients who achieved serum urate levels <360 μmol/L within 1 year of initiating urate-lowering therapy demonstrated a higher weighted 5-year MACE-free survival rate and a lower risk of MACE compared with those who did not achieve target levels. These findings were similar across multiple analyses, including alternative MACE definitions, censoring at therapy discontinuation, exclusion of patients lacking urate measurements in the first year, and component-specific outcomes.
The cardiovascular protective effect appeared more pronounced in older patients. Investigators reported an interaction between age and urate-lowering strategies, with a significantly greater effect size among individuals aged over 65 years compared with those aged under 65 years. A significantly lower number of flares was also recorded in people who achieved the serum urate target.
Efficacy and Safety of Investigational URAT1 Inhibitors
Two investigational URAT1 inhibitors demonstrated superior efficacy and favorable safety profiles compared with standard allopurinol therapy in separate Phase II and Phase III clinical trials.
Pozdeutinurad (AR882) Long-term Safety Outcomes
18-month safety data from a Phase II open-label trial of pozdeutinurad in patients with subcutaneous tophi were presented. Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity, with higher incidence during the first 6 months. Gout flare was the most frequent TEAE early in treatment, decreasing over time. Four serious adverse events were reported in three patients; however, none were considered related to pozdeutinurad, allopurinol, or flare prophylaxis. No elevations in serum creatinine or clinically significant liver function abnormalities were observed. Two patients developed renal stones—one with and one without a history of nephrolithiasis—but both events were mild to moderate, required no treatment, and resolved with no or only brief therapy interruption. Investigators concluded that these findings support pozdeutinurad as a poteintially safe treatment option for patients with gout, including those with clinically visible and subclinical urate crystal deposition.
Ruzinurad Phase III Efficacy and Safety Results
In a 52-week randomized, double-blind, active-controlled trial, Huihua Ding and colleagues compared ruzinurad with allopurinol in 773 patients with hyperuricemia associated with primary gout. During the initial 16-week double-blind period, 388 patients received ruzinurad and 385 received allopurinol. At Week 16, a significantly greater proportion of patients in the ruzinurad group achieved the target serum urate level (≤360 μmol/L) at both the last 2 monthly measurements (39.7% vs 26.5%) and overall (52.6% vs 34.5%). These differences were maintained through Week 52.
Treatment-emergent adverse events occurred in 89.7% of patients receiving ruzinurad and 91.7% of those receiving allopurinol. The most common events included gout flare, increased alanine aminotransferase, upper respiratory tract infection, and elevated blood creatinine. Most events were mild or moderate in severity. Serious TEAEs occurred in 4.9% of ruzinurad-treated patients and 3.1% of those in the allopurinol group. Investigators concluded that ruzinurad demonstrated superior urate-lowering efficacy compared with allopurinol, along with a well-tolerated safety profile.
Both novel URAT1 inhibitors demonstrated significant and sustained reductions in serum urate, along with reductions in clinically visible subcutaneous tophi and total urate crystal deposition, suggesting potential advantages over current standard therapies.
Disclosures were not provided at the time of publication.
Source: EULAR Press Release
