Early Marker Found for Long-Term Gout Flare Potential

Gout flares were markedly more common in patients with relatively high serum urate levels early on, researchers found.

Compared with patients with urate levels below 6 mg/dL at baseline, those with serum urate at 10 mg/dL or more faced an 11.26-fold higher risk for flares (95% CI 7.47-16.97) over 10 years of follow-up after adjusting for numerous factors that influence disease severity — including use of urate-lowering medications, according to Natalie McCormick, PhD, of Massachusetts General Hospital in Boston, and colleagues, who analyzed data on some 3,600 patients in the UK Biobank.

Flare risk showed a kind of dose-response relationship, with steadily increasing rates in parallel with higher baseline urate levels, the researchers reported in JAMA.

With levels less than 6 mg/dL as the reference, adjusted risk ratios over 10 years for intermediate degrees of elevated baseline urate were as follows:

6.0-6.9: 3.16 (95% CI 2.41-4.13)7.0-7.9: 6.20 (95% CI 4.79-8.03)8.0-8.9: 7.77 (95% CI 5.94-10.15)9.0-9.9: 9.80 (95% CI 7.14-13.44)

Put another way, each 1 mg/dL increment in baseline urate corresponded to a 1.58-fold increase in risk for flares.

McCormick and colleagues found an even more massive increase in risk for gout hospitalizations with higher baseline urate levels, which also was unaffected by urate-lowering therapy: patients with baseline urate of 10 mg/dL or more had a 45-fold higher risk for hospitalization relative to those with baseline urate below 6 mg/dL.

In an accompanying editorial, Angelo Gaffo, MD, MSPH, of the University of Alabama at Birmingham, said the study “adds valuable epidemiological evidence to support future prospective gout clinical trials testing the value of serum urate as a clinical predictor and as a biomarker amenable to clinical intervention to guide secondary prevention.”

Gaffo cautioned, however, that the research came with important limitations: an overwhelmingly white patient population that also had fewer comorbidities than is typical in gout. Moreover, serum urate can vary over short periods and yet only one reading was used in the study.

He called for more rigorous prospective studies, “designed for testing serum urate thresholds as treatment goals as well as their effect on meaningful clinical outcomes for patients with gout,” and which enroll samples that better match the real-world patient population.

For the current study, McCormick’s group pulled UK Biobank data for patients in Great Britain who had been diagnosed with gout and who had linked primary-care records. (This latter criterion eliminated 55% of Biobank participants with gout, the researchers noted.) Biobank participants were enrolled from 2006 to 2010; data through March 2020 were analyzed.

Serum urate was measured when patients first joined the Biobank, not when first diagnosed; time between initial diagnosis and urate measurement was not reported. However, after the baseline assessment, which also included extensive data collection on comorbidities and lifestyle factors (e.g., coffee and alcohol consumption and smoking status), participants were followed for 10 years. Flares were identified from primary care records, including new prescriptions for drugs commonly prescribed for gout attacks. Hospital records, of course, indicated patients admitted for gout treatment.

Mean patient age at baseline was about 60, and some 85% were men. Only about 10% of patients had serum urate levels of 9 or higher at baseline. Those with high levels tended to have higher BMI values and comorbidities such as hypertension and chronic kidney disease. They were also less likely to be on urate-lowering therapy at baseline.

Nevertheless, McCormick and colleagues found that overall risk for flares was nearly identical whether or not they were on urate-lowering therapy at baseline. For each 1-mg/dL increment in baseline urate, the risk ratios were 1.50 for those on anti-urate medications versus 1.56 for those not (P=0.35). In fact, only about 15% of patients in the study were on such treatment at baseline.

“These findings support using a baseline serum urate to assess risk of recurrent gout over nearly 10 years of follow-up,” the group concluded.

John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

The study was funded by the NIH.

McCormick disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. A co-author disclosed support from the Rheumatology Research Foundation Scientist Development Award, the NIH, and the NIH Loan Repayment Program. A co-author disclosed relationships with Horizon, LG Chem, Shanton, and ANI Pharmaceuticals. A co-author is an employee of Regeneron.

Gaffo disclosed relationships with PK MED, SOBI/Selecta, Atom, and UptoDate.

Primary Source

JAMA

Source Reference: McCormick N, et al “Serum urate and recurrent gout” JAMA 2024; DOI: 10.1001/jama.2023.26640.

Secondary Source

JAMA

Source Reference: Gaffo A “Serum urate and its association with gout flares” JAMA 2024; DOI: 10.1001/jama.2023.20110.

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