What is the recommended treatment for gout?

Treatment of Gout

Allopurinol is the preferred first-line urate-lowering therapy for all patients with gout, including those with moderate-to-severe chronic kidney disease, and should be started at a low dose (≤100 mg/day, lower in CKD) with gradual titration to achieve a serum urate target of <6 mg/dL. 1

Acute Gout Flare Management

For acute gout attacks, initiate treatment immediately with one of the following options based on patient comorbidities:

• Low-dose colchicine (1.2 mg at first sign of flare, followed by 0.6 mg one hour later; maximum 1.8 mg over one hour) 1, 2
• NSAIDs at anti-inflammatory doses 1
• Corticosteroids (oral, intra-articular, or intramuscular) 1

All three options are equally effective; choose based on contraindications and comorbidities 1. The most critical factor for success is how rapidly treatment is initiated, not which agent is selected. 3

Common Pitfall to Avoid

Higher doses of colchicine (>1.8 mg) are not more effective and increase toxicity risk 2. The old regimen of repeated hourly dosing is obsolete and dangerous 2.

Urate-Lowering Therapy (ULT)

Indications for Starting ULT

Strongly recommend initiating ULT for: 1

• Tophaceous gout
• Radiographic damage from gout
• Frequent gout flares (≥2 per year)

Conditionally recommend initiating ULT for: 1

• First gout flare (though this is debated)

First-Line ULT: Allopurinol

Allopurinol is the preferred first-line agent for all patients, including those with CKD stage ≥3. 1

Dosing strategy: 1

• Start at ≤100 mg/day (50-100 mg/day in moderate-severe CKD) 1
• Titrate gradually every 2-4 weeks to achieve target serum urate
• Maintenance doses can exceed 300 mg/day, even in patients with CKD, with appropriate monitoring 1

Target serum urate: 1

• <6 mg/dL (360 μmol/L) for all patients
• <5 mg/dL (300 μmol/L) for patients with severe gout (tophi, chronic arthropathy, frequent attacks)

HLA-B*5801 Screening

Prior to starting allopurinol, consider HLA-B*5801 screening for: 1

• Patients of Han Chinese, Korean, or Thai descent
• Koreans with CKD stage ≥3

This one-time test identifies patients at very high risk for severe allopurinol hypersensitivity syndrome 1.

Second-Line ULT Options

If allopurinol is contraindicated, not tolerated, or fails to achieve target serum urate at appropriate doses:

Febuxostat: 1, 4

• Start at 40 mg/day 1, 4
• Titrate to 80 mg/day if needed after 2-4 weeks 4
• Does not require dose adjustment in moderate CKD 1, 4
• Important caveat: In patients with history of cardiovascular disease who develop a new CV event while on febuxostat, switch to alternative ULT 1

Uricosuric agents (probenecid, benzbromarone): 1

• Consider as alternatives to xanthine oxidase inhibitors
• Probenecid: start 500 mg once or twice daily, titrate as needed 1
• Contraindicated in patients with renal calculi or significant renal impairment 3

Combination therapy: 1

• Combine a xanthine oxidase inhibitor with a uricosuric agent when monotherapy fails to achieve target

Third-Line: Pegloticase

Reserve pegloticase for patients with severe, refractory gout in whom all other therapies have failed or are contraindicated. 1 This is an expensive biologic requiring parenteral administration 1.

Prophylaxis Against Flares When Starting ULT

When initiating any ULT, strongly recommend concomitant anti-inflammatory prophylaxis for at least 3-6 months: 1

• Colchicine 0.6 mg once or twice daily (up to 1.2 mg/day) 1, 2
• NSAIDs (if colchicine contraindicated or not tolerated) 1
• Low-dose corticosteroids (if both colchicine and NSAIDs contraindicated) 1

Continue prophylaxis until serum urate has been at target for several months and patient is flare-free 1, 5. For patients with tophi, extend prophylaxis for 6 months 5.

Critical Pitfall

Failure to provide prophylaxis when starting ULT is a major cause of treatment failure and patient non-adherence. 4 Patients must be educated that initial flares are expected due to urate mobilization from tissue deposits 2.

Timing of ULT Initiation

ULT can be started during an acute gout flare if the decision has been made that ULT is indicated. 1, 6 This contradicts older teaching but is supported by recent evidence showing no prolongation of acute attacks when allopurinol is initiated during a flare with appropriate anti-inflammatory coverage 6.

Treat-to-Target Strategy

Strongly recommend a treat-to-target approach: 1

• Monitor serum urate levels regularly (every 2-4 weeks initially, then every 6 months once stable)
• Titrate ULT dose to achieve and maintain target serum urate <6 mg/dL
• Continue ULT indefinitely; do not stop once target is achieved 1

Management of Tophi

Tophi should be treated medically by achieving sustained serum urate reduction, preferably <5 mg/dL (300 μmol/L). 1 Surgery is only indicated in selected cases such as nerve compression, mechanical impingement, or infection 1.

Lifestyle Modifications

Advise all patients: 1

• Reduce excess body weight
• Perform regular exercise
• Smoking cessation
• Avoid excess alcohol (especially beer) and sugar-sweetened drinks
• Limit purine-rich foods (organ meats, shellfish)
• Encourage consumption of low-fat dairy products and vegetables 5

Special Populations

Renal Impairment

• Allopurinol remains first-line in CKD stage ≥3, but start at lower doses (50-100 mg/day) and titrate carefully 1
• Febuxostat does not require dose adjustment in mild-moderate renal impairment 1, 4
• For colchicine dosing in renal impairment, see specific FDA guidance for prophylaxis and acute treatment 2

Cardiovascular Disease

• Review diuretic use; loop and thiazide diuretics increase uric acid levels 5
• Consider losartan (increases uric acid excretion) if antihypertensive needed 5
• If patient on febuxostat develops new CV event, switch to alternative ULT 1

What NOT to Do

Do not treat asymptomatic hyperuricemia pharmacologically to prevent gout, renal disease, or cardiovascular events. 1 Treatment is only indicated for patients with established gout.