When should uric acid lowering therapy be initiated in patients with hyperuricemia?

When to Start Uric Acid Lowering Drugs in Hyperuricemia

Uric acid lowering therapy (ULT) should not be initiated for asymptomatic hyperuricemia (serum urate >6.8 mg/dL without gout flares or tophi), but should be started in patients with specific clinical presentations of gout or high-risk features. 1

Strong Indications for Starting ULT

• Presence of tophi: ULT is strongly recommended for patients with one or more subcutaneous tophi 1
• Radiographic damage: ULT is strongly recommended when there is radiographic damage (any modality) attributable to gout 1
• Frequent gout flares: ULT is strongly recommended for patients experiencing ≥2 gout flares per year 1

Conditional Indications for Starting ULT

• History of multiple flares: ULT is conditionally recommended for patients who have experienced >1 flare but have infrequent flares (<2/year) 1
• First flare with high-risk features: ULT is conditionally recommended for patients experiencing their first flare with any of the following:
  • Chronic kidney disease (CKD) stage ≥3 1
  • Serum urate >9 mg/dL 1
  • History of urolithiasis 1

Asymptomatic Hyperuricemia

• Generally not treated: For patients with asymptomatic hyperuricemia (SU >6.8 mg/dL with no prior gout flares or tophi), ULT is conditionally recommended against 1
• Rationale: Clinical trials show that only 20% of patients with asymptomatic hyperuricemia with SU >9 mg/dL develop gout within 5 years, and 24 patients would need treatment for 3 years to prevent a single gout flare 1

Special Considerations for CKD Patients

• CKD and symptomatic hyperuricemia: ULT is recommended for people with CKD and symptomatic hyperuricemia 1
• First gout episode in CKD: Consider initiating ULT after the first gout episode in adults with CKD, particularly with no avoidable precipitant or serum uric acid >9 mg/dL 1
• Medication choice: Xanthine oxidase inhibitors (like allopurinol) are preferred over uricosuric agents in people with CKD and symptomatic hyperuricemia 1, 2

Treatment Considerations

• Starting dose: All ULTs should be started at a low dose and then titrated upward until the SU target is reached 1
• Target levels: Serum urate should be maintained at <6 mg/dL (360 μmol/L) long-term 1
• Lower targets: A lower SU target (<5 mg/dL; 300 μmol/L) may facilitate faster crystal dissolution in patients with severe gout (tophi, chronic arthropathy, frequent attacks) 1
• First-line agent: Allopurinol is recommended as the preferred first-line agent, even in patients with moderate-to-severe CKD 1, 3

Common Pitfalls to Avoid

• Undertreating established gout: Failing to initiate ULT in patients with clear indications can lead to progressive joint damage and tophi formation 1, 2
• Treating asymptomatic hyperuricemia without indication: Treating all patients with asymptomatic hyperuricemia exposes many to potential medication risks without clear benefit 1
• Inadequate dosing: Starting and maintaining allopurinol at low doses (e.g., 100 mg daily) without titration often fails to reach target urate levels 1, 3
• Neglecting CKD patients: Despite high prevalence of gout in CKD, less than 25% of these patients are effectively treated to target serum urate levels 2

By following these evidence-based recommendations, clinicians can appropriately identify patients who would benefit from ULT while avoiding unnecessary treatment in those unlikely to progress to symptomatic disease.