Gout flares are associated with cardiovascular events. Treating gout to target serum urate level prevents flares, but whether such treatment can also prevent cardiovascular events is unknown. An abstract from Edoardo Cipolletta and colleagues explored whether achieving serum urate levels of less than 360 μmol/L within 1 year of the first prescription of urate-lowering therapy has an effect on the 5-year risk of major adverse cardiovascular events (MACE). The authors used English and Swedish primary-care data linked to hospitalisation and mortality records for over 116,000 patients. Overall, 16,201 patients had a MACE during follow-up. After meta-analysis, patients who achieved a serum urate of 360 μmol/L or less within 1 year had a higher weighted 5-year MACE-free overall survival and lower risk of MACE compared with those who did not. The findings were similar in analyses exploring different MACE definitions, when follow-up was censored on therapy discontinuation, when patients without available serum urate during the first year of follow-up were excluded, and when each component of MACE was considered separately. The authors noted there was an interaction between age and urate-lowering strategies, since the effect size in people aged over 65 was significantly greater than those aged 65 or under. Additionally, a significantly lower number of flares was recorded in people achieved the serum urate target.
New therapies are in development for urate lowering. Pozdeutinurad (AR882) is a novel and selective URAT1 inhibitor which has demonstrated significant sustained reduction in serum urate, as well as marked reduction in both clinically visible subcutaneous tophi, and total urate crystal deposition. Robert Keenan presented long-term safety and tolerability of pozdeutinurad alone or in combination with allopurinol in gout patients with subcutaneous tophi – data from a Phase 2 open-label trial. Over 18 months, most treatment-emergent adverse events (TEAE) were mild or moderate in severity, with higher numbers in the first 6 months. Gout flare – as expected – was the most frequent AE observed in the first 6 months, with a decreasing trend in subsequent periods. There were four serious adverse events reported in three patients, but none were considered related to pozdeutinurad, allopurinol, or therapy for flare prophylaxis. There were no serum creatinine elevations or clinically significant liver function abnormalities. Renal stones were found in two patients – one with and one without a history of nephrolithiasis – but they were considered mild to moderate, did not require treatment, and both patients completed the study with no or only brief interruption of therapy. 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.
Phase 3 data for ruzinurad – another URAT1 inhibitor – were presented by Huihua Ding. During a 16-week double-blind period, 388 patients received ruzinurad and 385 allopurinol. At Week 16, significantly greater proportions in the ruzinurad group achieved the target serum urate level of ≤360 μmol/L at the last two monthly measurements, compared with the allopurinol group – 39.7% versus 26.5%. The proportion achieving the serum urate target at Week 16 was 52.6% in the ruzinurad group compared to 34.5% with allopurinol – a difference which was maintained until Week 52. During the 52-week treatment period, TEAE occurred in 89.7% and 91.7% of patients in the ruzinurad and allopurinol groups, respectively, with the most common being gout flares, increased alanine aminotransferase, upper respiratory tract infection, and increased blood creatinine. The majority of TEAE were mild or moderate, but serious TEAE occurred in 4.9% and 3.1% of patients in the ruzinurad and allopurinol groups, respectively. The authors conclude that ruzinurad demonstrated superior urate-lowering over allopurinol, and showed a well-tolerated safety profile in patients with hyperuricemia associated with primary gout.
Source
Cipolletta E, et al. Cardiovascular outcomes of treat-to-target versus fire-and-forget urate-lowering treatment in gout: emulated target trial studies using linked English and Swedish primary care, hospitalisation and mortality data. Presented at EULAR 2025; OP0005. Ann Rheum Dis 2025; DOI: 10.1136/annrheumdis-2025-eular.B1714.
Khanna P, et al. Safety and Tolerability of Pozdeutinurad (AR882) Treatment following Long-term Dosing in Patients with Chronic Gouty Arthritis and Subcutaneous Tophi. Presented at EULAR 2025; OP0300. Ann Rheum Dis 2025; DOI: 10.1136/annrheumdis-2025-eular.B1720.
Ding H, et al. Ruzinurad for hyperuricemia associated with primary gout: a multicenter, randomized, double-blind, active-controlled, phase 3 study. Presented at EULAR 2025; OP0302. Ann Rheum Dis 2025; DOI: 10.1136/annrheumdis-2025-eular.B872.
References
1. Richette P, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76:29–42. DOI: 10.1136/annrheumdis-2016-209707.
About EULAR
EULAR is the European umbrella organisation representing scientific societies, health professional associations and organisations for people with rheumatic and musculoskeletal diseases (RMDs). EULAR aims to reduce the impact of RMDs on individuals and society, as well as improve RMD treatments, prevention, and rehabilitation. To this end, EULAR fosters excellence in rheumatology education and research, promotes the translation of research advances into daily care, and advocates for the recognition of the needs of those living with RMDs by EU institutions.
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