At what uric acid level should a patient with hyperuricemia start medication, what medication is recommended, and for how long should it be taken?

When to Start Urate-Lowering Therapy for Hyperuricemia

Do not start medication for asymptomatic hyperuricemia (elevated uric acid without symptoms), regardless of the level, unless specific high-risk features are present. 1

Asymptomatic Hyperuricemia: Generally No Treatment

• The American College of Rheumatology conditionally recommends against initiating urate-lowering therapy (ULT) for asymptomatic hyperuricemia, defined as serum urate >6.8 mg/dL with no prior gout flares or subcutaneous tophi. 1

• Even at very high levels (>9 mg/dL), only 20% of patients with asymptomatic hyperuricemia develop gout within 5 years, making the number needed to treat prohibitively high (24 patients for 3 years to prevent a single gout flare). 1

• Treatment of asymptomatic hyperuricemia is not recommended to prevent cardiovascular disease, renal disease, or gouty arthritis, despite epidemiologic associations with these conditions. 1

When to Start Medication: Symptomatic Hyperuricemia

Strong Indications (Start Treatment Immediately)

Start urate-lowering therapy if the patient has ANY of the following: 1, 2

• ≥2 gout flares per year 1, 2
• One or more subcutaneous tophi (visible or palpable uric acid deposits under the skin) 1, 2
• Radiographic damage attributable to gout (on any imaging modality) 1, 2
• Chronic tophaceous gout or urate arthropathy 2, 3

Conditional Indications (Consider Treatment)

Consider starting urate-lowering therapy after the first gout flare if ANY of these high-risk features are present: 1, 2

• Chronic kidney disease (CKD) stage ≥3 1, 2, 3
• Serum uric acid >9 mg/dL 1, 2, 3
• History of kidney stones (urolithiasis) 1, 2, 3
• Young age (<40 years) 2

Also consider treatment for patients with >1 previous gout flare but infrequent attacks (<2/year). 1, 2

What Medication to Start

First-Line: Allopurinol

Allopurinol is strongly recommended as the preferred first-line agent for all patients, including those with moderate-to-severe chronic kidney disease. 1, 2, 4

Starting Dose

• Start with 100 mg daily in patients with normal renal function 1, 2, 4
• Start with 50 mg daily in patients with CKD stage 4 or worse (creatinine clearance <30 mL/min) 1, 2, 4
• With creatinine clearance 10-20 mL/min, use 200 mg daily maximum 4
• With creatinine clearance <10 mL/min, do not exceed 100 mg daily 4

Dose Titration

• Increase the dose by 100 mg every 2-5 weeks until target serum uric acid is achieved 1, 2, 4
• Target serum uric acid: <6 mg/dL (360 μmol/L) for all patients 1, 2, 4
• Lower target of <5 mg/dL (300 μmol/L) for severe gout with tophi, chronic arthropathy, or frequent attacks until resolution 1, 2
• Maximum dose: 800 mg daily 1, 4
• Most patients require 300-600 mg daily to achieve target 4

Monitoring During Titration

• Check serum uric acid every 2-5 weeks during dose escalation 1, 2
• Once target is achieved, monitor every 6 months 1

Critical: Flare Prophylaxis When Starting Treatment

Always provide anti-inflammatory prophylaxis when initiating urate-lowering therapy to prevent gout flares. 1, 2, 4

Prophylaxis Options

• First choice: Colchicine 0.5-1 mg daily 1, 2

  • Reduce dose in renal impairment 1
  • Avoid with strong P-glycoprotein/CYP3A4 inhibitors 1

• Alternative if colchicine contraindicated: Low-dose NSAIDs 1, 2

• Alternative: Low-dose glucocorticoids 1

Duration of Prophylaxis

Continue prophylaxis for at least 6 months after starting urate-lowering therapy, or until serum uric acid has been normalized and the patient has been free from acute gouty attacks for several months. 1, 2, 4

How Long to Continue Treatment

Urate-lowering therapy should be continued lifelong once initiated. 1

• The European League Against Rheumatism explicitly states that serum urate <6 mg/dL should be maintained lifelong in patients with a history of gout. 1

• Discontinuation might be considered only in highly selected patients meeting ALL of these criteria: 1

  • At least 5 years of continuous ULT
  • Serum urate consistently <6 mg/dL
  • Complete resolution of tophi
  • No gout flares for at least 2-3 years
  • No chronic kidney disease stage ≥3
  • Not on diuretics

• If discontinuation is attempted, monitor serum urate every 3 months for the first year, then every 6 months, and immediately restart if uric acid rises above 6 mg/dL. 1

Common Pitfalls to Avoid

• Do not treat asymptomatic hyperuricemia even at very high levels (>9 mg/dL) without gout symptoms or high-risk features. 1

• Do not start allopurinol at 300 mg daily without checking renal function first; always start low and titrate. 1, 4

• Do not fail to provide flare prophylaxis when starting treatment—this is a major cause of treatment failure and non-adherence. 1

• Do not stop allopurinol during an acute gout flare; continue the current dose and treat the flare separately with anti-inflammatory medication. 2

• Do not stop treatment after a few years unless the patient meets strict criteria for discontinuation; lifelong therapy is the standard. 1