What is the recommended acute and long‑term treatment for gout, including NSAIDs, colchicine, corticosteroids, urate‑lowering therapy (allopurinol, febuxostat, probenecid), prophylaxis, lifestyle modifications, and options for refractory disease such as pegloticase?

Treatment for Gout

Acute Gout Flare Management

For an acute gout attack, initiate therapy within 24 hours of symptom onset using NSAIDs, colchicine, or corticosteroids as first-line monotherapy; the choice depends on renal function, cardiovascular risk, gastrointestinal comorbidities, and drug interactions. 1

Treatment Selection Algorithm

Step 1: Assess timing and contraindications

• If symptom onset ≤36 hours and no contraindications exist: colchicine is most effective when started within 12 hours 1
• If symptom onset >36 hours: do not use colchicine; select NSAIDs or corticosteroids instead 1
• Initiate any therapy within 24 hours for optimal efficacy; delays markedly reduce effectiveness 1

Step 2: Evaluate renal function

• eGFR <30 mL/min (severe renal impairment): use oral prednisone 30–35 mg daily for 5 days; both NSAIDs and colchicine are contraindicated 1, 2, 3
• eGFR 30–59 mL/min (moderate impairment): prednisone is safest; if colchicine is selected, reduce prophylactic dose to 0.6 mg once daily and monitor closely 1
• eGFR ≥60 mL/min: all three options are appropriate 1

Step 3: Screen for drug interactions

• If patient takes strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, erythromycin, cyclosporine, ketoconazole, ritonavir, verapamil): colchicine is absolutely contraindicated due to fatal toxicity risk, especially with any renal or hepatic impairment 1
• Select corticosteroids or NSAIDs instead 1

Step 4: Assess cardiovascular and gastrointestinal risk

• Heart failure, established cardiovascular disease, active peptic ulcer disease, recent GI bleeding, or anticoagulation therapy: avoid NSAIDs; use prednisone 30–35 mg daily for 5 days 1, 2, 3
• Cirrhosis or hepatic impairment: NSAIDs are contraindicated; prednisone is preferred 1, 3

Step 5: Consider joint involvement

• Monoarticular or oligoarticular gout (1–2 large, accessible joints): intra-articular corticosteroid injection (triamcinolone 40 mg for knee, 20–30 mg for ankle) provides targeted relief with minimal systemic exposure 1, 2
• Polyarticular gout (≥4 joints) or severe attacks: initiate combination therapy such as colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent 1
• Avoid combining systemic NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 1

Specific Dosing Regimens

Colchicine (if ≤36 hours from onset and no contraindications):

• Loading dose: 1.2 mg orally at first sign, followed 1 hour later by 0.6 mg (total 1.8 mg) 1
• After 12-hour pause: resume 0.6 mg once or twice daily until attack resolves 1
• This low-dose regimen achieves ≥50% pain reduction (NNT 3–5) with significantly fewer gastrointestinal adverse effects (23% diarrhea) compared to obsolete high-dose protocols (77% diarrhea) 1

NSAIDs (if no renal, cardiovascular, or GI contraindications):

• Use full FDA-approved anti-inflammatory doses throughout the entire attack without early tapering 1
• Options: naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily 1
• No single NSAID is superior; selection should be based on availability and individual tolerance 1

Oral corticosteroids (preferred in renal impairment, cardiovascular disease, or GI risk):

• Fixed-dose regimen (simplest): prednisone 30–35 mg once daily for 5 days without taper 1, 2, 3
• Alternative weight-based regimen: prednisone 0.5 mg/kg/day for 5–10 days at full dose then stop, or 2–5 days at full dose followed by 7–10 day taper for severe attacks 1, 2
• Level A evidence supports equivalency to NSAIDs with fewer adverse events (27% vs 63%) 1, 2

Parenteral corticosteroids (when oral route unavailable):

• Intramuscular triamcinolone acetonide 60 mg single injection is preferred over IL-1 inhibitors or ACTH 1, 2
• Intravenous methylprednisolone 0.5–2.0 mg/kg (40–140 mg for most adults) can be repeated as needed 1, 2

Critical Pitfalls to Avoid

• Do not initiate colchicine after 36 hours from symptom onset; efficacy declines sharply 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 taper NSAIDs early; maintain full dose throughout the attack until complete resolution 1
• Do not combine colchicine with strong CYP3A4/P-gp inhibitors in patients with any renal or hepatic impairment due to fatal toxicity risk 1
• Do not discontinue existing urate-lowering therapy (allopurinol or febuxostat) during an acute flare 1

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Long-Term Urate-Lowering Therapy (ULT)

Initiate urate-lowering therapy only after the acute flare has completely resolved, starting with low-dose allopurinol (≤100 mg daily) and titrating upward every 2–4 weeks until serum urate falls below 6 mg/dL. 1

Indications to Start 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
• Patient preference for early intervention 1
• Age <40 years at disease onset 1
• Urolithiasis 1

Allopurinol Initiation and Titration

"Start low, go slow" protocol:

• Starting dose: 100 mg daily (or 50 mg daily if CrCl 30–50 mL/min) 1
• Titration: increase 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
• This gradual approach reduces both acute flares and allopurinol hypersensitivity syndrome 1

Genetic screening:

• In patients with CKD stage ≥3 (especially Korean populations), screen for HLA-B*58:01 allele before starting allopurinol due to markedly increased risk of fatal hypersensitivity reactions 1

Serum Urate Targets

• Standard target: <6 mg/dL for all gout patients, maintained lifelong 1
• Aggressive target: <5 mg/dL for severe gout (tophi, chronic arthropathy, frequent attacks) until crystal dissolution 1
• Avoid maintaining serum urate <3 mg/dL long-term 1

Alternative ULT Agents

Febuxostat:

• Indicated when allopurinol at appropriate dose fails to achieve target or when allopurinol is intolerable 1
• Starting dose: 40 mg daily; titrate to 80 mg (or 120 mg if needed) 1
• Does not require renal dose adjustment in mild-to-moderate CKD 1

Uricosuric agents (probenecid, benzbromarone):

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

Pegloticase:

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

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Prophylaxis During ULT Initiation

When starting or adjusting urate-lowering therapy, provide colchicine 0.6 mg once or twice daily for at least 6 months to prevent acute flares triggered by urate mobilization. 1

Prophylaxis Regimen

First-line prophylaxis:

• Colchicine 0.6 mg once or twice daily for at least 6 months 1
• Continue for 3 months after achieving target serum urate <6 mg/dL if no tophi present 1
• Continue for 6 months after achieving target if tophi are present 1
• High-quality RCT evidence shows colchicine reduces flare proportion from 77% to 33% (p=0.008) during allopurinol initiation 1

Second-line prophylaxis (if colchicine contraindicated):

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

Renal impairment dose adjustments:

• CrCl 30–80 mL/min: reduce colchicine prophylaxis to 0.6 mg once daily 1
• CrCl <30 mL/min: start colchicine at 0.3 mg once daily with close monitoring, or avoid entirely and use alternative prophylaxis 1

Critical Management Points

• Do not omit prophylaxis; 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 initiate allopurinol at 300 mg daily; starting at high dose increases risk of flares and hypersensitivity syndrome 1
• Do not stop ULT during an acute flare if the patient is already on therapy; continue and treat the flare separately 1

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Lifestyle Modifications

Weight loss and regular physical activity lower excess mortality associated with hyperuricemia. 1

Dietary recommendations:

• Limit: alcohol (especially beer and spirits), sugar-sweetened beverages, fructose-rich foods, large meals, excessive meat/seafood 1
• Encourage: low-fat dairy, coffee, cherries 1

Medication review:

• Replace loop or thiazide diuretics when possible 1
• Consider losartan or calcium-channel blockers for hypertension 1
• Use statins or fenofibrate for hyperlipidemia 1

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Refractory Disease Options

For patients with frequent flares who have contraindications to colchicine, NSAIDs, and corticosteroids, IL-1 inhibitors (canakinumab 150 mg subcutaneously) are reserved as second-line therapy. 1, 3

• Current infection is an absolute contraindication to IL-1 blocker use 3
• At least 12 weeks should elapse between doses 3