Low Serum Uric Acid Levels Significantly Reduce Gout Risk

High serum uric acid (SUA) levels are associated with a high risk of new-onset gout and gout recurrence, while lowering SUA levels can significantly reduce incident and recurrent gout. These study results were published in The Journal of Rheumatology.¹

Gout can cause inflammatory arthritis via monosodium urate (MSU) crystal formation in the joints and tissues, resulting in severe joint pain, swelling, and redness. The risk of developing cardiovascular disease and diabetes — along with increased mortality — is also elevated in patients with gout.¹

Treating hyperuricemia with a target SUA level <6.0 mg/dL can cure gout by preventing the formation of MSU crystals and enabling existing MSU crystals to dissolve. Curing gout reduces the risk of joint damage, other chronic conditions, and early mortality.¹ In addition, the American College of Rheumatology and European League Against Rheumatism recommend treating gout to a goal of an SUA level <6.0 mg/dL.^2,3 However, SUA reduction in gout is not widely practiced by clinicians, leading to under-treatment of gout.¹

Researchers evaluated the relationship between SUA levels and the risk of new-onset and recurrent gout in a systematic review.¹

Increasing SUA levels were associated with a progressively higher risk for new-onset gout. The risk for incident gout was 70.2 new cases per 1000 person-years with an SUA level ≥10 mg/dL and 0.8 new cases with an SUA level ≤6 mg/dL, based on 3 prospective population-based studies.¹

Pooled data from 5 studies measuring SUA levels prior to gout flares showed that the risk of gout flares was lowest with an SUA level ≤6 mg/dL (12%) and highest with an SUA level ≥9 mg/dL (61%) in patients treated with urate-lowering therapy (ULT). In patients in whom ULT was considered successful, the risk of flares ranged from 3.7% (SUA 6 to 7 mg/dL) to 61% (SUA >9.3 mg/dL).¹

These trends were sustained with mean SUA levels. A mean SUA level of 6.4 mg/dL was associated with 2 flares per year per patient, while a mean SUA level of 9.0 mg/dL was associated with 4.6 flares per year per patient, based on 10 studies that evaluated mean flares based on SUA level.¹

Summary and Clinical Applicability

Gout is an inflammatory arthritis that can cause joint pain and damage, as well as chronic conditions such as cardiovascular disease. While lowering SUA to a target <6.0 mg/dL can cure gout and improve prognosis, treating to this SUA target is not widely practiced. Researchers demonstrated that lower SUA levels are associated with markedly lower rates of new-onset gout and gout flares in patients on ULT.

“Although few prospective cohorts have evaluated incident and recurrent gout according to SUA, the existing evidence underscores the need to treat to SUA targets, as recommended by the American College of Rheumatology and the European League Against Rheumatism,” the researchers wrote.¹

Limitations and Disclosures

• Studies categorized patients using different SUA thresholds, with SUA level cutoffs ranging from <8 mg/dL to <9 mg/dL in high-risk patients
• The timing of measuring SUA levels prior to the onset of gout or gout flares varied between studies

This study was supported by Takeda Pharmaceuticals International, Inc.

References

1. Shiozawa A, Szabo SM, Bolzani A, Cheung A, Choi HK. Serum uric acid and the risk of incident and recurrent gout: a systematic review. J Rheumatol. 2017;44(3):388-396. doi:10.3899/jrheum.160452
2. Khanna D, Fitzgerald JD, Khanna PP, et al; American College of Rheumatology. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-1446. doi:10.1002/acr.21772
3. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2016;76:29-42. doi:10.1136/annrheumdis-2016-209707