In an adult patient with gout, how should I treat an acute flare and initiate long‑term urate‑lowering therapy to prevent recurrences and joint damage?

Management of Acute and Chronic Gout

Acute Gout Flare Treatment

For an acute gout flare, initiate therapy within 24 hours using NSAIDs, low-dose colchicine, or corticosteroids, selecting based on patient contraindications and cost—all three options are equally effective at reducing pain. 1, 2

First-Line Pharmacologic Options

• NSAIDs should be administered at full anti-inflammatory doses (e.g., naproxen 500 mg twice daily or indomethacin 50 mg three times daily) and continued until complete symptom resolution. 1, 2
• Low-dose colchicine (1.2 mg followed by 0.6 mg one hour later, maximum 1.8 mg total) is as effective as higher doses but causes significantly fewer gastrointestinal adverse effects. 1, 3
• Corticosteroids (oral prednisone 30–35 mg daily for 5–10 days, intra-articular injection, or intramuscular administration) are appropriate when NSAIDs or colchicine are contraindicated. 1, 2, 4

Treatment Goals and Monitoring

• Target ≥20% pain reduction within 24 hours and ≥50% reduction by 48 hours. 2
• If pain improvement is <20% at 24 hours, add another agent or switch to an alternative therapy. 2
• The most critical determinant of success is how rapidly treatment is initiated, not which specific agent is chosen. 2, 5

Common Pitfall

Never delay acute flare treatment beyond 24 hours, as this significantly compromises therapeutic effectiveness. 2

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Indications for Initiating Urate-Lowering Therapy (ULT)

Start ULT in patients with ≥2 gout attacks per year, presence of tophi, radiographic gout damage, chronic kidney disease stage ≥3, serum uric acid >9 mg/dL, or history of uric acid kidney stones. 1, 2

Strong Indications (Initiate ULT)

• Frequent gout flares (≥2 per year) 1, 2
• One or more subcutaneous tophi 1, 2
• Radiographic damage attributable to gout (any imaging modality) 1, 2
• Chronic kidney disease stage ≥3 1, 2
• History of urolithiasis 1, 2

When NOT to Initiate ULT

• Do not start ULT after a single gout attack in patients without other high-risk features. 1, 2
• Do not start ULT in patients with infrequent attacks (<2 per year) unless other indications are present. 1

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Timing of ULT Initiation Relative to Acute Flare

When ULT is indicated, start it during the acute flare rather than waiting for flare resolution, provided effective anti-inflammatory therapy and prophylaxis are simultaneously administered. 2, 6, 4

• Randomized trials demonstrate that initiating ULT during a flare does not prolong flare duration or increase severity when appropriate anti-inflammatory coverage is provided. 2, 6
• If a patient is already on established ULT when a flare occurs, continue the ULT without interruption—stopping it may cause serum urate fluctuations that worsen or prolong the attack. 6

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Urate-Lowering Therapy: Drug Selection and Dosing

First-Line Agent: Allopurinol

Allopurinol is the preferred first-line urate-lowering agent. 1, 2, 7

• Starting dose: 100 mg daily 2, 7
• Titration: Increase by 100 mg every 1–2 weeks (some guidelines suggest weekly, others every 2–5 weeks) 2, 7
• Target: Serum uric acid <6 mg/dL (360 µmol/L); consider <5 mg/dL if tophi are present 2, 7
• Maximum dose: 800 mg daily 7
• Dose adjustments in CKD:
  • CrCl 10–20 mL/min: 200 mg daily 7
  • CrCl <10 mL/min: ≤100 mg daily 7
  • Allopurinol can be safely dose-escalated in CKD with appropriate monitoring 2

Alternative Agent: Febuxostat

• Febuxostat 40 mg daily lowers serum urate as effectively as allopurinol 300 mg daily. 1, 2
• Adverse effects include abdominal pain, diarrhea, and musculoskeletal pain. 1, 2
• Consider febuxostat in patients with allopurinol hypersensitivity or inadequate response. 1

Uricosuric Agents

• Probenecid is an option for patients who are allopurinol-allergic, have normal renal function, no history of urolithiasis, and are urate underexcretors. 5

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Treat-to-Target Strategy

ULT must be titrated based on serial serum urate measurements to achieve and maintain a target <6 mg/dL (360 µmol/L)—this treat-to-target approach is strongly recommended over fixed-dose regimens. 2, 7

• Monitor serum uric acid every 2–5 weeks during titration, then every 6 months once target is achieved. 2
• A serum uric acid <6 mg/dL stays below the saturation threshold for monosodium urate crystal formation (6.8 mg/dL). 2

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Mandatory Anti-Inflammatory Prophylaxis During ULT Initiation

All patients starting ULT must receive concomitant anti-inflammatory prophylaxis to prevent gout flares—this is non-negotiable. 1, 2, 4

Why Prophylaxis is Essential

• ULT does not reduce gout attacks during the first 6 months and may initially increase flare frequency due to mobilization of urate from tissue deposits. 2, 8
• High-quality evidence shows prophylaxis reduces acute gout attacks by at least 50% when starting ULT. 1, 4

First-Line Prophylaxis Options

Agent	Typical Dose
Colchicine (low-dose)	0.5–0.6 mg once or twice daily [1,2,4,3]
NSAID (e.g., naproxen)	250 mg twice daily [1,2,9]
Corticosteroid (if colchicine/NSAID contraindicated)	Low-dose prednisone/prednisolone [2,9]

Duration of Prophylaxis

• Minimum duration: 3 months after ULT initiation 2, 4
• Optimal duration: 3–6 months, or 3 months after achieving target serum urate 2, 4
• Prophylaxis extending beyond 8 weeks is significantly more effective than shorter durations—flares roughly double when prophylaxis is stopped after only 8 weeks. 1, 2
• Extend prophylaxis beyond 6 months if flares persist or the serum urate target has not yet been reached. 2, 4

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Critical Pitfalls to Avoid

• Never initiate ULT without concurrent anti-inflammatory prophylaxis—this dramatically raises flare risk. 2, 4
• Never discontinue prophylaxis before 3 months—premature cessation leads to preventable flares. 2, 9
• Never use a fixed-dose ULT regimen without monitoring and titration—a treat-to-target approach is superior. 2
• Never stop established ULT during an acute flare—serum urate fluctuations may worsen or prolong the attack. 6

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Special Considerations

Chronic Kidney Disease

• Allopurinol can be safely dose-escalated in CKD patients with appropriate dose adjustments based on creatinine clearance. 2, 7
• Worse renal function modestly reduces urate-lowering efficacy; larger body size and concomitant diuretic use may necessitate higher allopurinol doses. 2

HLA-B*5801 Testing

• Consider HLA-B*5801 testing before starting allopurinol in patients of Southeast Asian descent due to increased risk of severe hypersensitivity reactions. 4

Cost Considerations

• When selecting among corticosteroids, NSAIDs, or colchicine for acute gout treatment, choose based on cost when no contraindications exist—colchicine, including generic versions, is the most expensive. 1

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Patient Education

• Emphasize the chronic nature of gout and the necessity of lifelong ULT adherence. 2
• Counsel on lifestyle modifications: weight loss, limiting alcohol and sugar-sweetened beverages, reducing intake of purine-rich organ meats and shellfish, and encouraging low-fat dairy products. 2
• Maintain fluid intake sufficient to yield daily urinary output of at least 2 liters. 7