What is the recommended acute and long‑term treatment plan for gout, including medication choices, dosing, and lifestyle measures?

Treatment of Gout

For acute gout flares, initiate therapy within 24 hours using NSAIDs, colchicine, or corticosteroids as first-line monotherapy—selected based on renal function, cardiovascular risk, and gastrointestinal comorbidities—and for long-term management, start allopurinol at 100 mg daily with colchicine prophylaxis once the acute attack resolves, titrating upward every 2–4 weeks to achieve serum urate <6 mg/dL. 1

Acute Gout Management

Timing of Treatment Initiation

• Begin pharmacologic therapy within 24 hours of symptom onset; delays beyond this window markedly reduce effectiveness of all agents. 1, 2
• Colchicine is most effective when started within 12 hours and should not be initiated after 36 hours from symptom onset. 1, 2

First-Line Monotherapy Options

Selection Algorithm:

1. Assess renal function first: If eGFR <30 mL/min → use corticosteroids only; avoid NSAIDs and colchicine. 1
2. Check for drug interactions: If patient takes strong CYP3A4/P-gp inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil) → avoid colchicine. 1, 3
3. Evaluate cardiovascular/GI risk: If heart failure, cardiovascular disease, cirrhosis, or peptic ulcer disease → prefer corticosteroids over NSAIDs. 1
4. Consider joint involvement: If 1–2 large accessible joints → consider intra-articular injection. 1

NSAIDs

• Use full FDA-approved anti-inflammatory doses throughout the entire attack without early tapering: naproxen 500 mg twice daily, indomethacin 50 mg three times daily, or sulindac 200 mg twice daily. 1, 2
• No single NSAID demonstrates superior efficacy; selection depends on availability and patient tolerance. 1
• Contraindications: severe renal impairment (eGFR <30 mL/min), heart failure, cirrhosis, active peptic ulcer disease, anticoagulation therapy. 1

Colchicine

• Loading dose: 1.2 mg orally at first sign of flare, followed 1 hour later by 0.6 mg (total 1.8 mg). 1, 3
• After a 12-hour pause, resume 0.6 mg once or twice daily until attack resolves. 1, 3
• This low-dose regimen achieves ≥50% pain reduction with number needed to treat of 3–5, equivalent efficacy to high-dose regimens (4.8 mg) but with significantly fewer gastrointestinal adverse effects (23% vs 77% diarrhea). 1, 2
• Absolute contraindications: severe renal impairment (CrCl <30 mL/min), concurrent strong CYP3A4 or P-gp inhibitors especially with any renal or hepatic impairment. 1, 3

Corticosteroids

• Oral prednisone: 0.5 mg/kg/day (approximately 30–35 mg) for 5–10 days at full dose then stop, or 2–5 days at full dose followed by 7–10 day taper. 1
• This regimen provides Level A evidence for efficacy equivalent to NSAIDs with fewer adverse events (27% vs 63%). 1
• Intra-articular injection: triamcinolone acetonide 40 mg for knee, 20–30 mg for ankle, for monoarticular or oligoarticular involvement of accessible large joints. 1
• Intramuscular option: triamcinolone acetonide 60 mg as single injection for patients unable to take oral medications. 1, 4
• Contraindications: active systemic fungal infection (absolute), current active infection (relative). 1, 4

Combination Therapy for Severe Attacks

• Indications: polyarticular gout (≥4 joints), multiple large joints involved, or severe pain not responding to monotherapy within 24 hours. 1, 2
• Recommended combinations: colchicine + NSAID, oral corticosteroid + colchicine, or intra-articular steroid + any oral agent. 1, 2
• Avoid: combining systemic NSAID with systemic corticosteroid due to synergistic gastrointestinal toxicity. 1, 2

Monitoring Response

• Inadequate response is defined as <20% improvement in pain within 24 hours OR <50% improvement at ≥24 hours after initiating therapy. 1, 5
• If inadequate response occurs, consider alternative diagnoses, switch to another monotherapy, or add a second agent. 1, 5

Long-Term Urate-Lowering Therapy (ULT)

Indications for Starting ULT

• Strong indications (start after first flare): subcutaneous tophi, radiographic joint damage from gout, chronic kidney disease stage ≥3. 1
• Conditional indications (start after first flare): patient preference, young age at onset (<40 years), serum urate >9 mg/dL (480 µmol/L), recurrent attacks (≥2 per year), urolithiasis. 1
• For uncomplicated first gout attack without high-risk features, ULT initiation may be deferred. 1

Timing of ULT Initiation

• Do not start ULT during an acute flare; wait until the attack has completely resolved. 1
• Do not discontinue existing ULT during an acute flare if patient is already on therapy. 1

Allopurinol: First-Line ULT

Initiation and Titration Protocol

• Start low: Begin at 100 mg daily (or 50 mg daily if CrCl 30–50 mL/min). 1, 6
• Go slow: Increase by 100 mg every 2–4 weeks until serum urate <6 mg/dL. 1, 6
• Most patients require 300–600 mg daily; maximum dose is 800 mg daily. 1, 6
• Allopurinol can be titrated above 300 mg daily even with renal impairment, with adequate patient education and monitoring for toxicity (pruritus, rash, elevated transaminases). 1

Renal Dose Adjustment

• With CrCl 10–20 mL/min: maximum 200 mg daily. 6
• With CrCl <10 mL/min: maximum 100 mg daily; may need to lengthen dosing interval. 6
• In CKD stage 3 or worse, consider HLA-B*5801 screening before initiation (especially in Korean, Han Chinese, and Thai populations) to reduce risk of severe hypersensitivity reactions. 1

Target Serum Urate Levels

• Standard target: <6 mg/dL (360 µmol/L) for all gout patients, maintained lifelong. 1
• Aggressive target: <5 mg/dL (300 µmol/L) for patients with severe gout (tophi, chronic arthropathy, frequent attacks) until total crystal dissolution. 1
• Do not maintain serum urate <3 mg/dL long-term. 1

Alternative ULT Agents

• Febuxostat: If allopurinol target not reached at appropriate dose, switch to febuxostat or combine allopurinol with uricosuric. 1
• Febuxostat is also indicated if allopurinol cannot be tolerated. 1
• Uricosuric agents (probenecid, benzbromarone): Use as alternative in patients with normal renal function; relatively contraindicated in urolithiasis. 1
• Pegloticase: Reserved for crystal-proven severe debilitating chronic tophaceous gout with poor quality of life when serum urate target cannot be reached with any other drug at maximal dose. 1

Prophylaxis During ULT Initiation

This is critical to prevent flares triggered by urate mobilization.

• First-line prophylaxis: Colchicine 0.6 mg once or twice daily for at least 6 months. 1
• Continue prophylaxis for 3 months after achieving target serum urate if no tophi present, or 6 months if tophi present. 1
• High-quality evidence shows colchicine prophylaxis reduces flare proportion from 77% to 33% during allopurinol initiation. 1
• Second-line prophylaxis (if colchicine contraindicated): low-dose NSAID with proton pump inhibitor, or low-dose prednisone (<10 mg/day). 1
• Avoid high-dose prednisone (>10 mg/day) for prophylaxis due to increased adverse effects without proportional benefit. 1

Lifestyle and Non-Pharmacologic Measures

• Weight loss if obese; regular physical activity reduces excess mortality associated with hyperuricemia. 1
• Dietary modifications:
  • Avoid or limit: alcohol (especially beer and spirits), sugar-sweetened drinks, foods rich in fructose, heavy meals, excessive meat and seafood intake. 1
  • Encourage: low-fat dairy products (especially skimmed milk and low-calorie yogurt), coffee, cherries. 1
• Medication review: If patient takes loop or thiazide diuretics, substitute if possible; for hypertension consider losartan or calcium channel blockers; for hyperlipidemia consider statin or fenofibrate. 1

Common Pitfalls to Avoid

• Do not delay acute treatment beyond 24 hours; effectiveness declines sharply. 1, 2
• Do not start colchicine after 36 hours from symptom onset; efficacy drops dramatically. 1, 2
• Do not taper NSAIDs early; maintain full dose throughout entire attack. 1, 2
• Do not start allopurinol at 300 mg daily; this increases risk of flares and hypersensitivity syndrome. 1
• Do not stop ULT during acute flare if patient already on therapy. 1
• Do not omit colchicine prophylaxis when starting ULT; flare rates double without it. 1
• Do not combine colchicine with strong CYP3A4/P-gp inhibitors in patients with any renal or hepatic impairment; risk of fatal toxicity. 1, 3
• Do not use obsolete high-dose colchicine regimen (0.5 mg every 2 hours); causes severe diarrhea in most patients with no additional benefit. 1, 2