How should I treat an acute gout flare and initiate long‑term urate‑lowering therapy, including drug choices, dosing, renal dose adjustments, prophylaxis, and options for refractory disease?

Gout Treatment: Comprehensive Management Algorithm

Acute Gout Flare Management

Timing is Critical

Initiate treatment within 12–24 hours of symptom onset for maximal effectiveness; delays beyond 24 hours markedly reduce the efficacy of all agents. 1

First-Line Treatment Selection (Based on Patient Factors)

For patients with normal renal function and no contraindications:

• NSAIDs (naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily) at full FDA-approved doses throughout the entire attack without early tapering 2, 1
• Colchicine 1.2 mg at first sign, followed 1 hour later by 0.6 mg (total 1.8 mg), then after 12-hour pause resume 0.6 mg once or twice daily until resolution—but only if started within 36 hours of symptom onset 1
• Oral prednisone 30–35 mg daily for 5 days (no taper needed) or 0.5 mg/kg/day for 5–10 days 2, 1, 3

For monoarticular or oligoarticular involvement of 1–2 large accessible joints:

• Intra-articular corticosteroid injection (triamcinolone 40 mg for knee, 20–30 mg for ankle) is highly effective and avoids systemic exposure 2, 1, 3

Contraindication-Driven Selection Algorithm

If eGFR < 30 mL/min (severe renal impairment):

• Use oral prednisone 30–35 mg daily for 5 days exclusively—colchicine and NSAIDs are absolutely contraindicated due to risk of fatal toxicity and acute kidney injury 1, 3, 4

If patient is on strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil):

• Colchicine is absolutely contraindicated—use NSAIDs or corticosteroids instead 1

If heart failure, established cardiovascular disease, cirrhosis, active peptic ulcer disease, or on anticoagulation:

• Avoid NSAIDs—use colchicine (if no drug interactions) or corticosteroids 1, 3

If unable to take oral medications:

• Intramuscular triamcinolone acetonide 60 mg single injection or intravenous methylprednisolone 0.5–2.0 mg/kg 2, 1, 4

Combination Therapy for Severe Attacks

For polyarticular gout (≥ 4 joints) or multiple large joints:

• Initiate combination therapy: colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent 2, 1
• Never combine systemic NSAID with systemic corticosteroid due to synergistic gastrointestinal toxicity 2, 1

Critical Pitfalls to Avoid in Acute Management

• Do not start colchicine after 36 hours from symptom onset—efficacy drops dramatically 1
• Do not taper NSAIDs early—maintain full dose throughout the attack 1
• Do not use obsolete high-dose colchicine regimens (0.5 mg every 2 hours)—they cause severe diarrhea without added benefit 1
• Do not discontinue existing urate-lowering therapy during an acute flare—continue allopurinol or febuxostat and treat the flare separately 1, 3

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Long-Term Urate-Lowering Therapy (ULT)

Indications to Initiate ULT

Strong indications (initiate after first flare):

• Subcutaneous tophi 1
• Radiographic joint damage attributable to gout 1
• Chronic kidney disease stage ≥ 3 1

Conditional indications:

• ≥ 2 gout attacks per year 1
• Serum urate > 9 mg/dL 1
• Age < 40 years at disease onset 1
• Patient preference for early intervention 1

Timing of ULT Initiation

Do not start ULT during an acute flare—wait until the attack has completely resolved 1

Allopurinol: First-Line ULT

Initiation protocol:

• Start at 100 mg daily (or 50 mg daily if CrCl 30–50 mL/min) 1
• Titrate upward by 100 mg every 2–4 weeks until serum urate < 6 mg/dL 1
• Typical maintenance dose: 300–600 mg daily; maximum 800 mg daily 1
• In patients with CKD stage ≥ 3 or Korean ethnicity, screen for HLA-B*58:01 allele before starting to prevent fatal hypersensitivity syndrome 1

Target serum urate:

• Standard target: < 6 mg/dL for all gout patients, maintained lifelong 1, 4
• Aggressive target: < 5 mg/dL for severe gout with tophi or chronic arthropathy until crystal dissolution 1

Alternative ULT Agents

Febuxostat:

• Indicated when allopurinol at appropriate dose fails to achieve target or is intolerable 1
• Start 40 mg daily, titrate to 80 mg (or 120 mg if needed) 1
• No renal dose adjustment required in mild-to-moderate CKD 1
• Caution: increased risk of cardiovascular death and heart failure hospitalization—avoid in patients with established cardiovascular disease 5

Uricosuric agents (probenecid, benzbromarone):

• Appropriate for patients with normal renal function 1
• Relatively contraindicated in those with history of urolithiasis 1

Pegloticase:

• Reserved for crystal-proven, severe, debilitating chronic tophaceous gout when all other therapies at maximal doses fail 1

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Mandatory Prophylaxis During ULT Initiation

First-Line Prophylaxis

Colchicine 0.6 mg once or twice daily:

• Start concurrently with the first dose of allopurinol or febuxostat 2, 1
• Continue for at least 6 months, or:
  • 3 months after achieving target serum urate < 6 mg/dL if no tophi present 2, 1
  • 6 months after achieving target if tophi are present 2, 1
• High-quality evidence shows colchicine prophylaxis reduces flare incidence from 77% to 33% during ULT initiation 1

Renal dose adjustments for colchicine prophylaxis:

• CrCl 30–80 mL/min: 0.6 mg once daily 1
• CrCl < 30 mL/min: 0.3 mg once daily with close monitoring, or avoid entirely 1

Second-Line Prophylaxis (If Colchicine Contraindicated)

• Low-dose NSAID with proton-pump inhibitor (e.g., naproxen 250 mg twice daily with omeprazole 20 mg daily) for ≥ 6 months 2, 1
• Low-dose prednisone < 10 mg/day for ≥ 6 months 2, 1, 3, 4

Critical Prophylaxis Pitfalls

• Do not omit colchicine prophylaxis when starting ULT—flare rates roughly double without it 1
• Do not stop prophylaxis early (before 3–6 months) merely because flares have ceased—premature cessation causes rebound flares 1
• Do not use high-dose prednisone (> 10 mg/day) for prophylaxis—it increases adverse effects without additional benefit 2, 1

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Special Populations

Severe Renal Impairment (eGFR < 30 mL/min) or ESRD

Acute flare:

• Oral prednisone 30–35 mg daily for 3–5 days or intra-articular corticosteroid injection 3, 4
• Avoid colchicine and NSAIDs entirely 3, 4

Long-term ULT:

• Allopurinol remains first-line but requires substantial dose reduction—start 50 mg daily and titrate slowly 4
• Target serum urate < 6 mg/dL 4

Prophylaxis:

• Low-dose prednisone 5–10 mg daily for 3–6 months is the safest option 4

Cardiovascular Disease or Heart Failure

Acute flare:

• Colchicine is safe and potentially reduces myocardial infarction risk 5
• Short-duration low-dose glucocorticoids are efficacious and may be safe 5
• Avoid NSAIDs due to cardiovascular and heart failure risks 5

Long-term ULT:

• Allopurinol or probenecid are first-line—safe with potential for reducing cardiovascular outcomes 5
• Avoid febuxostat—increased risk of cardiovascular death and heart failure hospitalization 5

Patients on Strong CYP3A4/P-gp Inhibitors

Absolute contraindication to colchicine when combined with clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, or verapamil—especially with any renal or hepatic impairment—due to risk of fatal toxicity 1

Elderly Patients with Multiple Comorbidities

Prednisone 30–35 mg daily for 5 days is the safest option when colchicine and NSAIDs carry unacceptable risks 1, 3

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Refractory Gout

For patients with frequent flares who have contraindications to colchicine, NSAIDs, and corticosteroids:

• IL-1 inhibitors (canakinumab 150 mg subcutaneously, with at least 12 weeks between doses) 3, 6
• Current infection is an absolute contraindication to IL-1 blockers 3

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Lifestyle and Non-Pharmacologic Measures

• Weight loss and regular physical activity lower excess mortality associated with hyperuricemia 1
• Dietary recommendations: limit alcohol (especially beer), sugar-sweetened beverages, fructose-rich foods, and excessive meat/seafood; encourage low-fat dairy, coffee, and cherries 1, 7
• Medication review: replace loop or thiazide diuretics when possible; consider losartan or calcium-channel blockers for hypertension; use statins or fenofibrate for hyperlipidemia 1
• Topical ice and rest of the inflamed joint are useful adjuncts during acute attacks 1, 8