As newer agents progress toward regulatory approval, these insights could inform a paradigm shift in gout management.
Pivotal findings unveiled at the European Alliance of Associations for Rheumatology Congress could redefine the management of gout, a disease still plagued by underdiagnosis and suboptimal treatment despite well-established guidelines.
EULAR continues to recommend maintaining serum urate levels below 6 mg/dL (360 μmol/L), and even more stringently below 5 mg/dL (300 μmol/L) in severe cases.
However, the challenge of achieving these targets in clinical practice remains evident. New data presented at the congress in Barcelona offers hope for more effective and safer urate-lowering strategies, along with emerging insights into the broader health implications of gout control.
Serum Urate Targets and Cardiovascular Risk
One of the standout presentations came from Dr Edoardo Cipolletta and colleagues, who assessed whether achieving a serum urate (sUA) level beneath 360 μmol/L within one year of starting urate-lowering therapy (ULT) reduced the five-year risk of major adverse cardiovascular events (MACE).
Dr Cipolletta and colleagues linked primary care data to hospitalisation and mortality records for more than 116,000 English and Swedish patients, identifying over 16,000 MACEs during their follow-up.
The findings were compelling – patients who reached the sUA target within one year had significantly higher MACE-free survival and a reduced risk of cardiovascular events. This association persisted across multiple sensitivity analyses and subgroups.
Related
Notably, the cardiovascular benefit was more pronounced in individuals aged over 65 years, suggesting age-dependent differences in treatment effect. Additionally, these patients experienced fewer gout flares, reinforcing the importance of sustained urate control.
Pozdeutinurad shows long-term promise
In a Phase 2 open-label study, Associate Professor Robert Keenan presented long-term safety and tolerability data for pozdeutinurad (AR882), a novel selective URAT1 inhibitor. The 18-month trial involved patients with chronic gout and subcutaneous tophi, exploring both monotherapy and combination with allopurinol.
Key findings included:
- Most treatment-emergent adverse events were mild to moderate, with a notable reduction in flare frequency after the initial six months.
- Four serious adverse events occurred; none linked to the study drugs.
- Renal stones developed in two patients, but these were manageable and non-disruptive to therapy.
- There were no concerning liver or renal function abnormalities.
The authors conclude that these results support pozdeutinurad as a safe option for the treatment of patients with gout, including those with both clinically visible and subclinical crystal deposition.
Ruzinurad vs Allopurinol: Phase 3 comparative efficacy
Huihua Ding presented Phase 3 data for ruzinurad, another URAT1 inhibitor, in a head-to-head comparison with allopurinol. In this randomized, double-blind study (n=773), ruzinurad demonstrated superior urate-lowering efficacy.
Highlights included:
- At Week 16, 52.6% of ruzinurad-treated patients achieved the target sUA level (≤360 μmol/L) compared with 34.5% in the allopurinol group.
- This efficacy was sustained through Week 52.
- Treatment-emergent adverse events were common (89.7% ruzinurad, 91.7% allopurinol), with gout flares being the most frequent. However, most events were mild or moderate.
- Serious treatment-emergent adverse events were relatively low (4.9% vs 3.1%) and did not raise new safety concerns.
The authors concluded that ruzinurad demonstrated superior urate-lowering over allopurinol and showed a well-tolerated safety profile in patients with hyperuricemia associated with primary gout.
Annals of the Rheumatic Diseases, June 2025
