Achievement of target serum urate levels is associated with a reduction in the number of gout flares, investigators report.

Using serum urate levels as a treatment target and trial endpoint became more controversial after the 2017 American College of Physicians guidelines recommended a treat-to-symptom rather than a treat-to-target approach to gout management.

In a post hoc analysis of 2 trials of urate-lowering therapy (mostly allopurinol), 91 of 343 (27%) patients who achieved a mean serum urate level of less than 6 mg/dL (responders) and 156 of 245 (64%) nonresponders experienced at least 1 gout flare at 12 to 24 months. Patients who achieved the target serum urate level had significant 71% decreased odds for gout flare compared with nonresponders, Lisa K. Stamp, MB ChB, PhD, of the University of Otago in Christchurch, New Zealand, and colleagues reported in The Lancet Rheumatology. Further, the mean number of gout flares per individual per month during the study period was a significant 0.41 lower among responders compared with nonresponders.  Responders also were more likely than nonresponders to have resolution of tophi.

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“Using individual patient-level data, we show that achieving a serum urate concentration of less than 6 mg/dL is associated with improvement in outcomes of importance to patients with gout,” Dr Stamp’s team wrote. “These results provide evidence for the treat-to-target serum urate approach in the management of gout.”

In an accompanying editorial, Thomas Bardin, MD, and Pascal Richette, MD, of the Université de Paris in Paris, France, commented, “It remains to be seen if this evidence, which is limited by the fact that it relies on a post-hoc analysis, will be enough to convince the ACP. The results of the planned TRUST study (NCT04875702), comparing a treat-to-target serum urate strategy versus a treat-to-avoid-symptoms strategy as advocated by the ACP, might be necessary to settle the issue.”

Additional research will be needed to confirm the optimal target serum urate threshold.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of authors’ disclosures.


Stamp LK, Frampton C, Morillon MB, et al. Association between serum urate and flares in people with gout and evidence for surrogate status: a secondary analysis of two randomised controlled trials. Lancet Rheum. Published online November 5, 2021. doi:10.1016/S2665-9913(21)00319-2

Bardin T, Richette P. Uricaemia as a surrogate endpoint in gout trials and the treat-to-target approach for gout management. Lancet Rheum. Published online November 5, 2021. doi:10.1016/S2665-9913(21)00358-1