What is the basis for initiating treatment in asymptomatic hyperuricemia with serum uric acid levels greater than 9 milligrams per deciliter (mg/dL)?

From the Guidelines

Treatment for asymptomatic hyperuricemia with serum uric acid levels above 9 mg/dL should generally not be initiated unless there are specific risk factors present, such as chronic kidney disease, history of urolithiasis, or other conditions that may increase the risk of gout progression or complications. The standard approach is to monitor these patients without pharmacologic intervention, as asymptomatic hyperuricemia alone does not typically warrant treatment 1. However, if the patient has comorbidities such as chronic kidney disease, history of urolithiasis, or is undergoing chemotherapy with high risk of tumor lysis syndrome, treatment may be considered. When treatment is deemed necessary, allopurinol is typically the first-line medication, starting at 100 mg daily and gradually titrating up to achieve a target uric acid level below 6 mg/dL. Febuxostat (40-80 mg daily) is an alternative for patients who cannot tolerate allopurinol. Probenecid (250-500 mg twice daily) may be used in patients with normal renal function. Lifestyle modifications should accompany any pharmacologic treatment, including weight loss if appropriate, limiting alcohol intake, reducing consumption of purine-rich foods, and maintaining adequate hydration. The rationale for generally avoiding treatment in asymptomatic hyperuricemia is that the risks of medication side effects often outweigh the benefits in patients without symptoms or complications.

Some key points to consider in the management of asymptomatic hyperuricemia include:

• The presence of comorbidities such as chronic kidney disease, history of urolithiasis, or other conditions that may increase the risk of gout progression or complications
• The use of allopurinol, febuxostat, or probenecid as first-line medications for urate-lowering therapy (ULT)
• The importance of lifestyle modifications, including weight loss, limiting alcohol intake, reducing consumption of purine-rich foods, and maintaining adequate hydration
• The need for shared decision-making between the patient and healthcare provider to determine the best course of treatment.

It is essential to note that the 2020 American College of Rheumatology guideline for the management of gout recommends against initiating ULT in patients with asymptomatic hyperuricemia, unless specific risk factors are present 1. The guideline suggests that the benefits of ULT may not outweigh the potential risks and costs for patients without symptoms or complications. Therefore, a careful evaluation of the patient's individual risk factors and medical history is necessary to determine the best approach to management.

From the FDA Drug Label

THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. The basis for initiating treatment in asymptomatic hyperuricemia with serum uric acid levels greater than 9 milligrams per deciliter (mg/dL) is not recommended.

• The drug label explicitly states that allopurinol is not recommended for the treatment of asymptomatic hyperuricemia. 2

From the Research

Basis for Initiating Treatment

The basis for initiating treatment in asymptomatic hyperuricemia with serum uric acid levels greater than 9 milligrams per deciliter (mg/dL) is not well-established. However, several studies provide guidance on this issue:

• Asymptomatic hyperuricemia should be treated only if the plasma uric acid levels are around 10 mg/100 ml or more on several determinations 3.
• Treatment may be considered for patients with very high levels of uric acid or those who are otherwise at risk of complications, such as those with a personal or strong family history of gout, urolithiasis, or uric acid nephropathy 4.
• In patients with chronic kidney disease, lowering the serum uric acid level may be associated with a slowing in the rate of renal deterioration 5.
• The decision to initiate treatment should take into account the individual's risk of cardiovascular and renal events, as asymptomatic hyperuricemia is considered an independent predictor of cardiovascular and all-cause mortality 6.

Key Considerations

When considering treatment for asymptomatic hyperuricemia, the following factors should be taken into account:

• Serum uric acid levels: Treatment may be considered for levels above 10 mg/100 ml 3.
• Risk of complications: Patients with a personal or strong family history of gout, urolithiasis, or uric acid nephropathy may require treatment 4.
• Presence of chronic kidney disease: Lowering serum uric acid levels may slow renal deterioration in these patients 5.
• Cardiovascular and renal risk: Asymptomatic hyperuricemia is associated with an increased risk of cardiovascular and renal events, and treatment may be considered to mitigate this risk 6.