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Natalie McCormick, PhD, an investigator in the Rheumatology & Allergy Clinical Epidemiology Research Center at the Mongan Institute at Massachusetts General Hospital and an instructor in Medicine at Harvard Medical School, is the lead author of a recently published paper in JAMA, Serum Urate and Recurrent Gout

What was the question you set out to answer with this study?

Can serum urate levels be used to predict the recurrence of gout, a painful form of inflammatory arthritis?

Gout is caused by chronically elevated serum urate levels and urate crystallization within joints.

We sought to quantify associations of target serum urate levels with recurrent flare rates, particularly the proportions of flares occurring above these target levels (i.e., ≥6 or ≥5 mg/dL) among gout patients, including flares requiring hospitalizations.

The association between serum urate levels and new onset gout has been documented, but analogous research about recurrent gout flares among those with preexisting gout has not been previously carried out.

What Methods or Approach Did You Use?

We used data from members of the UK Biobank (UKBB) cohort who had gout at the time of enrollment. Serum urate was measured from labs drawn at enrollment.

History of gout and gout flares during the study period were identified from linked medical records.

Other variables such as smoking status, baseline medication use, body mass index, and dietary intake were self-reported or measured at the time of UKBB enrollment.

We counted the number of gout flares each person with gout had over the study period, and compared gout flare rates across different categories of serum urate at baseline.

A feature of this study was that serum urate measurements were obtained from all gout patients at the study baseline, irrespective of clinical needs or flare status.

Since gout flares are known to substantially lower serum urate levels, this approach helps to avoid exposure misclassification, which can occur if investigators are relying on serum urate measures obtained when patients seek care for potential flares (as happens in studies using serum urate measurements from health claims or electronic health record data).

Such exposure misclassification could underestimate the relation between serum urate levels and recurrent flares.

What Did You Find?

Higher levels of serum urate were strongly associated with the frequency of recurrent flares and their hospitalizations in a graded manner. 95% and 98% of flares occurred in those with baseline serum urate levels ≥6 and ≥5 mg/dL, respectively, the thresholds in the US/European and British rheumatology guidelines.

Associations were more prominent for hospitalized flares, with no cases among those with serum urate < 5mg/dL.

What Are the Implications?

Most (> 90%) of gout care occurs in primary care settings, but the value of relying on target urate levels has not been widely accepted in primary care practice, and the American College of Physicians instead endorses a treat-to-avoid symptoms approach.

Our findings support the value of target serum urate levels in gout flare prevention in primary care and provide evidence that 95% and 98% of gout flares can be potentially preventable at the population level if the serum urate targets (<6 and <5 mg/dL, respectively) are met.

As such, targeting these serum urate levels for gout patient care as per rheumatology guidelines would help reduce the gout flare burden tremendously.

What Are the Next Steps?

Next steps include developing a strategy to effectively implement these target serum urate goals in primary clinical practices and beyond. To develop a sustainable strategy, we will have to remain cognizant of the fact that these practices also manage multiple conditions that are comorbid with gout.

Approaches involving nurses, pharmacists, or interactive digital health systems (as in other chronic treat-to-target care such as anticoagulation care, blood pressure or lipid care) are currently being researched.

Paper cited:

McCormick, N., Yokose, C., Challener, G. J., Joshi, A. D., Tanikella, S., & Choi, H. K. (2024). Serum Urate and Recurrent Gout. JAMA331(5), 417–424. https://doi.org/10.1001/jama.2023.26640

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system.