Serum Urate in Chronic Gout — Will It Be the First Validated Soluble Biomarker in Rheumatology?

Abstract

Objective To summarize evidence for and endorsement of serum urate (SU) as having fulfilled the OMERACT filter as a soluble biomarker in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). Methods Data were presented to support the use of SU as a soluble biomarker in chronic gout and specifically the ability to utilize it to predict future patient-reported outcomes. Results SU was accepted as having fulfilled the OMERACT filter by 78% of voters. However, consensus was not obtained regarding its use as a soluble biomarker in chronic gout. Although the majority of the criteria for a soluble biomarker were fulfilled, the key criterion of association of the biomarker with outcomes was not agreed upon. It was agreed that the appropriate choice of endpoint must be linked to its clinical importance to the individual with the disorder and its temporal relationship to the intervention. Appropriate outcomes in chronic gout may therefore include gout flares, reduction in tophi, and patient-reported outcomes. Conclusion SU is a critical outcome measure. It has the potential to fulfil criteria for a soluble biomarker. Further analyses of existing data from randomized controlled trials will be required to determine whether SU can predict future important outcomes, in particular disability.

Gout: an Asia‐Pacific update

“…47 The Gout Special Interest Group is trying to identify domains of interest and is now evaluating a series of outcomes for features of chronic gout, such as serum uric acid level, physical measurement or digital photography of tophi and imaging modalities. 48,49 Gout-specific patient reported outcome instruments like the Gout Assessment Questionnaire (GAQ) were also developed that collect information about gout impact, assessing pain, well-being, productivity and treatment satisfaction. A modified version of this instrument GAQ 2.0 contains a Gout Impact Scale (GIS) and four other sections that gather clinical, background and economic data.…”

Development and First Validation of a Disease Activity Score for Gout

“…Tissue deposits of uric acid (UA) are the best candidate to measure disease activity in gout because they reflect a still ongoing active disease process 1. Serum UA (sUA) approximates tissue levels well, and it is the main target of treatment in gout 2.…”

Outcome Measures for Gout Clinical Trials: a Summary of Progress

“…OMERACT has previous identified serum urate (SU) as an important outcome measure in chronic gout studies, which is understandable given that the underlying biochemical abnormality in gout is hyperuricaemia [5,14]. Despite all guidelines recommending a treat to a SU target, there is a remarkably small literature that clearly shows that changes in SU in response to treatment are associated with clinically relevant outcomes in randomised controlled trials, with only a trial of pegloticase correlating changes in SU with health-related quality of life and an observational study that showed velocity of tophus regression was associated with degree of urate lowering [1••, 25].…”

“…OMERACT-specific criteria for soluble biomarkers have been developed and adapted for chronic gout studies [5]. At OMERACT 10 in 2010, SU was found to fulfil many of the OMERACT requirements but there was no consensus that it should be endorsed as a biomarker in chronic gout studies, given the lack of research that clearly documents the link between treatment-induced urate lowering and patientrelevant outcomes [5].…”

“…Despite all guidelines recommending a treat to a SU target, there is a remarkably small literature that clearly shows that changes in SU in response to treatment are associated with clinically relevant outcomes in randomised controlled trials, with only a trial of pegloticase correlating changes in SU with health-related quality of life and an observational study that showed velocity of tophus regression was associated with degree of urate lowering [1••, 25]. OMERACT-specific criteria for soluble biomarkers have been developed and adapted for chronic gout studies [5]. At OMERACT 10 in 2010, SU was found to fulfil many of the OMERACT requirements but there was no consensus that it should be endorsed as a biomarker in chronic gout studies, given the lack of research that clearly documents the link between treatment-induced urate lowering and patientrelevant outcomes [5].…”