What is the recommended treatment for a patient with chronic gout?

Chronic Gout Treatment

Start allopurinol at 100 mg/day (or ≤50 mg/day if CKD stage ≥3) with mandatory anti-inflammatory prophylaxis, titrate by 100 mg every 2-4 weeks until serum uric acid is <6 mg/dL, and maintain this target lifelong. 1

First-Line Urate-Lowering Therapy

Allopurinol is the strongly recommended first-line agent for all patients with chronic gout, including those with moderate-to-severe chronic kidney disease. 1 This recommendation is based on its proven efficacy when dosed appropriately (often requiring >300 mg/day up to the FDA-approved maximum of 800 mg/day), excellent tolerability, safety profile, and lower cost compared to alternatives. 1, 2

Critical Dosing Strategy

• Always start low and titrate up: Begin with ≤100 mg/day in patients with normal renal function, and ≤50 mg/day in those with CKD stage ≥3. 1, 3
• Increase by 100 mg increments every 2-4 weeks until the serum uric acid target is achieved. 1, 2
• Do not stop at 300 mg/day: Most patients require doses above 300 mg/day to reach target uric acid levels; the maximum FDA-approved dose is 800 mg/day. 1, 2
• Adjust for renal impairment: With creatinine clearance 10-20 mL/min, use 200 mg/day maximum; with clearance <10 mL/min, do not exceed 100 mg/day. 2

Common pitfall: Starting at 300 mg/day significantly increases the risk of allopurinol hypersensitivity syndrome, particularly in patients with any degree of renal impairment. 4, 3

Serum Uric Acid Targets

• Standard target: <6 mg/dL (360 μmol/L) for all patients on urate-lowering therapy, maintained lifelong. 1, 3
• Lower target: <5 mg/dL (300 μmol/L) for patients with severe gout (tophi, chronic arthropathy, frequent attacks) until complete crystal dissolution and resolution of gout. 1
• Avoid: <3 mg/dL long-term as this is not recommended. 1

Monitor serum uric acid levels regularly to guide dose titration until target is reached. 3

Mandatory Anti-Inflammatory Prophylaxis

All patients starting urate-lowering therapy must receive concomitant anti-inflammatory prophylaxis to prevent acute flares. 4, 3 This is non-negotiable regardless of whether starting during or after an acute flare.

Prophylaxis Options (in order of preference):

• Colchicine 0.5-1 mg/day is the preferred first-line prophylactic agent. 4, 3
• Low-dose NSAIDs (if no contraindications). 3
• Low-dose corticosteroids (prednisone/prednisolone 5-10 mg/day) are particularly appropriate in patients with heart failure, CKD, or NSAID contraindications. 4, 3

Duration: Continue prophylaxis for 3-6 months after initiating urate-lowering therapy, with extended prophylaxis if flares persist. 3

When to Initiate Urate-Lowering Therapy

Urate-lowering therapy should be discussed with every patient from first presentation and is definitively indicated in: 1

• All patients with recurrent flares
• Presence of tophi
• Urate arthropathy
• Renal stones
• Young age at presentation (<40 years)
• Very high serum uric acid (>8.0 mg/dL)
• Comorbidities including renal impairment, hypertension, ischemic heart disease, or heart failure

You can start urate-lowering therapy during an acute flare if the flare is adequately treated with anti-inflammatory agents; delaying offers no clinical benefit. 4, 5

Second-Line Options

If allopurinol fails to achieve target serum uric acid at appropriate doses or is not tolerated:

• Febuxostat (start at ≤40 mg/day, titrate to 80 mg/day if needed) is strongly recommended over probenecid in patients with CKD stage ≥3. 1
• Probenecid (start 500 mg once to twice daily with dose titration) can be used in patients with normal renal function and no history of urolithiasis. 1
• Combination therapy: Allopurinol can be combined with a uricosuric agent if target is not reached with allopurinol alone. 1
• Benzbromarone (where available) is highly effective even in mild-to-moderate renal impairment but carries a small risk of hepatotoxicity. 1

Severe Refractory Gout

Pegloticase is indicated only for crystal-proven, severe debilitating chronic tophaceous gout with poor quality of life when the serum uric acid target cannot be reached with any other available drug at maximal dosage (including combinations). 1, 6 It is strongly recommended against as first-line therapy due to cost and potential adverse effects. 1

Pegloticase is administered as 8 mg IV infusion every 2 weeks, requires premedication with antihistamines and corticosteroids, and carries significant risk of anaphylaxis and infusion reactions. 6

Lifestyle Modifications (Essential Adjunct)

Every patient with gout must receive comprehensive lifestyle advice: 1

• Weight loss if appropriate (proven to reduce serum uric acid)
• Avoid: Alcohol (especially beer and spirits), sugar-sweetened drinks, foods rich in fructose, excessive meat and seafood intake
• Encourage: Low-fat dairy products (especially skimmed milk and low-calorie yogurt), regular exercise, adequate hydration (≥2 liters daily urinary output)
• Consider: Coffee and cherry consumption (associated with lower gout risk)

Medication Adjustments

When gout occurs in patients on diuretics or with comorbidities: 1

• Substitute diuretics if possible (loop or thiazide diuretics increase gout risk)
• For hypertension: Consider losartan or calcium channel blockers
• For hyperlipidemia: Consider statin or fenofibrate

Critical Monitoring

• Monitor serum uric acid prior to each infusion if using pegloticase; consider discontinuing if levels increase above 6 mg/dL, particularly with 2 consecutive elevated levels. 6
• Check renal function before starting allopurinol and periodically during treatment. 3
• Continue monitoring serum uric acid until target is achieved and maintained. 3

Common pitfall: Do not discontinue urate-lowering therapy during acute flares; continue treatment and manage the flare separately with anti-inflammatory agents. 4, 5