Association of Serum Urate Levels With Subsequent Gout Flares
Individuals with gout often experience regular, recurrent gout flares that can not only greatly diminish a patient’s quality of life, but also lead to permanent joint damage, pain, and disability.
Serum urate levels have long been targeted in the treatment of individuals with gout, but knowledge gaps have remained on the relationship between these serum urate levels and the rate of recurrent gout among these patients.
Researchers recently conducted a retrospective study examining the association between higher levels of serum urate and the incidence of subsequent gout flares among patients with a history of gout.1 Lead study author Hyon K. Choi, MD, DrPH, discusses these study findings and their implications with Consultant360.
Consultant360: How did this study come about?
Hyon K Choi, MD, DrPH: There are two approaches to gout care; treat-to-target serum urate (TTT-SU), where serum urate values are measured regularly until patients reach the target (eg, <6 or <5 mg/dL, urate sub-saturation points), or treat-to-avoid-symptoms (TTASx), where gout flares are treated as needed without regularly measuring serum urate. US and European rheumatology guidelines endorse the TTT-SU approach, but the value of relying on target urate levels is not accepted in primary care practice where most (>90%) gout care occurs. Indeed, serum urate is not followed in primary care practice, even after initiation of urate-lowering therapy, in the vast majority of gout patients. Instead, TTASx, not relying on target urate levels, has often been adopted, as endorsed by the latest American College of Physicians guidelines. To that end, the proportions of flares associated with these target levels among gout patients, including those requiring hospitalizations, were unknown before our study.
C360: Could you give an overview of what was previously known about the relationship between serum urate and the risk of gout?
Dr Choi: Gout is caused by urate crystallization within the joints. Accumulation of urate within the joint is due to chronic hyperuricemia with serum urate levels exceeding the saturation point for uric acid crystallization in the body (ie, approximately 7 mg/dL). To that end, prior studies have found strongly graded associations between serum urate levels above the saturation point and the risk of developing new cases of gout among individuals without gout at baseline. However, associations between serum urate levels and the risk of recurrent flares among preexisting patients with gout, which is relevant to clinical gout care practice, has not been established in prospective studies. As such, despite the emphasis in US and European rheumatology guidelines on the use of urate-lowering therapy to treat-to-target serum urate level, the proportions of flares associated with such target urate levels remained unknown.
C360: In addition to finding that 100% of new gout flares leading to hospitalization occurred in patients with a serum urate of 5 mg/dL or greater, your study also found that 97% of new gout flares leading to hospitalization had a sodium urate of 6 mg/dL or greater. What is the importance of this finding?
Dr Choi: This was particularly important because hospitalizations for gout are a costly and burdensome source of health care utilization. For example, annual US hospitalization rates due to gout have recently doubled, in contrast to hospitalization rates due to rheumatoid arthritis, which have declined over recently years.2 However, our findings show that at the population level, nearly all hospitalizations for gout could be prevented with serum urate less than 6 mg/dL and all hospitalizations could be prevented with serum urate less than 5 mg/dL.
C360: How do you expect the results of this study to impact clinical practice?
Dr Choi: We showed that 95% and 98% of gout flares can be potentially preventable at the population level if serum urate less than 6 and less than 5 mg/dL can be met, respectively; 100% of hospitalizations for gout could be preventable with serum urate less than 5mg/dL. As such, targeting these serum urate levels as per rheumatology guidelines would help reduce the gout flare burden tremendously. In particular, these findings support the value of target serum urate levels for gout flare prevention in primary care, where most gout patients are treated.
C360: What are the next steps for research in this area?
Dr Choi: The next research includes implementation science on how to achieve these target serum urate goals effectively in primary clinical practices and beyond, which can become readily overwhelmed by multiple comorbidities. Involving nurses, pharmacists, or interactive online or app systems (as in other chronic treat-to-target care such as anticoagulation care, blood pressure, or lipid care) is actively being researched. Also, we are trying to find the effective and safe medications and non-pharmacologic measures to reduce the urate burden, which can also simultaneously take care of gout’s frequent cardiovascular-kidney comorbidities (eg, SGLT2i or effective obesity care).
C360: Is there anything else you would like to add?
Dr Choi: An important 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 minimizes potential exposure misclassification, which often occurs when serum urate is measured when patients seek care for potential flares (as happens routinely in studies using serum urate measurements from health claims or electronic health record data). As such, those prior studies failed to reveal the truly compelling nature of relations between serum urate levels and recurrent flares among pre-existing gout patients.
References:
- McCormick N, Yokose C, Challener GJ, Joshi AD, Tanikella S, Choi HK. Serum urate and recurrent gout. JAMA. 2024;331(5):417-424. doi:10.1001/jama.2023.26640
- Lim SY, Lu N, Oza A, et al. Trends in gout and rheumatoid arthritis hospitalizations in the United States, 1993-2011. JAMA. 2016;315(21):2345-2347. doi:10.1001/jama.2016.3517.