Towards a more ambitious uricemia target to improve joint and cardiovascular outcomes in gout

Abstract

Gout is the most common inflammatory arthritis and a global health problem. In addition to joint involvement, urate crystals induce chronic inflammation, leading to increased cardiovascular risk in gout. Thus, cardiovascular disease is the leading cause of death in gout and numerous studies have revealed an increase in cardiovascular-related mortality in these patients. However, despite the efficacy of urate-lowering therapies, such as allopurinol and febuxostat, suboptimal management of gout and poor adherence continue to make it difficult to achieve better outcomes. Treat-to-target strategy may help change this, as in other diseases such as rheumatoid arthritis. Nevertheless, even with a well-defined clinical target (absence of flares and tophi disappearance), the numerical target [serum uric acid (SUA) < 5 mg/dL or < 6 mg/dL] still varies depending on current guidelines and consensus documents. Recently, several trials [Long-Term Cardiovascular Safety of Febuxostat Compared with Allopurinol in Patients with Gout (FAST), REasons for Geographic And Racial Differences in Stroke (REGARDS)] have shown better cardiovascular outcomes in those patients who achieve SUA levels < 5 mg/dL. Likewise, some observational studies, mostly based on imaging tests such as ultrasound and dual-energy computed tomography, have found better results in the magnitude and speed of reduction of urate joint deposition when SUA < 5 mg/dL is achieved. Based on an analysis of the available evidence, SUA < 5 mg/dL is postulated as a more ambitious target within the treat-to-target approach for the management of gout to achieve better joint and cardiovascular outcomes in patients with cardiovascular risk or severe disease.