What is the recommended management and treatment for gout?

Management and Treatment of Gout

Acute Gout Flare Treatment

For acute gout flares, initiate treatment immediately with colchicine, NSAIDs, or corticosteroids as first-line therapy, choosing based on patient comorbidities and contraindications. 1

First-Line Treatment Options (All Equally Effective)

• Colchicine: 1.2 mg at first sign of flare, followed by 0.6 mg one hour later (maximum 1.8 mg over one hour). 1, 2

  • Most effective when started within 12 hours of symptom onset 3, 4
  • Low-dose colchicine is strongly preferred over high-dose due to similar efficacy with fewer adverse effects 1
  • Critical contraindications: Avoid in severe renal impairment (GFR <30 mL/min) and with strong CYP3A4/P-glycoprotein inhibitors (cyclosporine, clarithromycin) due to risk of fatal toxicity 3, 2

• NSAIDs: Full FDA-approved doses (e.g., naproxen 250 mg twice daily) with proton pump inhibitor if gastrointestinal risk exists 1, 4

  • Contraindications: Severe renal impairment, heart failure, cirrhosis, cardiovascular disease 5, 3

• Oral corticosteroids: Prednisone/prednisolone 30-35 mg daily for 3-5 days 1, 3, 4

  • Preferred option in patients with severe CKD (GFR <30 mL/min) where colchicine and NSAIDs must be avoided 3
  • No dose adjustment needed for renal or hepatic impairment 3
  • Alternative regimen: 0.5 mg/kg/day for 5-10 days then stop, or 0.5 mg/kg/day for 2-5 days then taper over 7-10 days 3

• Intra-articular corticosteroids: For monoarticular or oligoarticular involvement (1-2 joints) 1, 3

• Parenteral glucocorticoids (intramuscular, intravenous): Strongly recommended when oral medications cannot be taken 1, 3

Combination Therapy for Severe Attacks

• For severe acute gout with multiple large joints or polyarticular involvement, initial combination therapy is appropriate 1, 3
• Acceptable combinations: colchicine + NSAIDs, oral corticosteroids + colchicine, or intra-articular steroids with any other modality 1, 3
• Avoid combining NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity 1

Second-Line Options

• IL-1 inhibitors (canakinumab): Conditionally recommended only when colchicine, NSAIDs, and corticosteroids are ineffective, poorly tolerated, or contraindicated 1, 3
• Contraindication: Current infection 3

Adjuvant Treatment

• Topical ice is conditionally recommended as adjuvant therapy 1, 3

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Urate-Lowering Therapy (ULT)

Initiate ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares (≥2 per year). 1

Indications for ULT

• Tophaceous gout 1
• Radiographic damage due to gout 1
• Frequent gout flares (≥2 per year) 1, 5
• Chronic kidney disease 5
• History of urolithiasis 5

First-Line ULT: Allopurinol

• Allopurinol is the preferred first-line ULT, including for patients with moderate-to-severe CKD (stage ≥3) 1
• Starting dose: ≤100 mg/day (lower in CKD) 1, 6
  • CKD with creatinine clearance 10-20 mL/min: 200 mg/day 6
  • CKD with creatinine clearance <10 mL/min: Maximum 100 mg/day 6
• Titration: Increase by 100 mg every 2-4 weeks (weekly intervals acceptable) 5, 4, 6
• Target: Serum uric acid <6 mg/dL 1, 5, 4
• Maximum dose: 800 mg/day 6

Alternative ULT Options

• Febuxostat: Starting dose <40 mg/day, clinically equivalent to allopurinol 1, 7
• Uricosuric agents (probenecid): For patients with preserved renal function and no history of nephrolithiasis 8, 7
• Pegloticase: Strongly recommended for patients where xanthine oxidase inhibitors, uricosurics, and other interventions have failed to achieve target serum urate AND who have frequent flares or nonresolving tophi 1
  • Strongly recommended against in patients with infrequent flares (<2/year) and no tophi due to harms and costs outweighing benefits 1

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Anti-Inflammatory Prophylaxis During ULT Initiation

When initiating ULT, concomitant anti-inflammatory prophylaxis is strongly recommended for at least 3-6 months. 1

First-Line Prophylaxis

• Low-dose colchicine: 0.6 mg once or twice daily (0.5 mg outside US) 1, 5, 4

Second-Line Prophylaxis

• Low-dose NSAIDs with proton pump inhibitor where indicated (e.g., naproxen 250 mg twice daily) 1
• Low-dose prednisone/prednisolone (<10 mg/day): Only if colchicine and NSAIDs are not tolerated, contraindicated, or ineffective 1, 3

Duration of Prophylaxis

• Minimum: 3 months after achieving target serum urate (no tophi) OR 6 months (if tophi present) 1
• At least 6 months from ULT initiation 1
• Continue longer if flares persist 4

Dose Adjustments for Renal Impairment

• Mild-moderate impairment (CrCl 30-80 mL/min): No adjustment needed, but monitor closely 2
• Severe impairment (CrCl <30 mL/min): Start 0.3 mg/day, increase cautiously 2
• Dialysis patients: 0.3 mg twice weekly 2

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Key Management Principles

Timing of ULT Initiation

• ULT can be started during an acute flare with appropriate anti-inflammatory coverage; no need to wait for flare resolution 3, 4
• Once started, do not stop ULT during acute attacks 4

Treat-to-Target Strategy

• Use serial serum urate measurements to guide ULT dose titration 1
• Target serum urate <6 mg/dL (360 μmol/L) 1, 5, 4

Lifestyle Modifications

• Limit purine-rich foods (organ meats, shellfish) 9
• Avoid alcohol (especially beer and spirits) and beverages with high-fructose corn syrup 5, 4, 9
• Encourage low-fat dairy products and vegetables 9
• Weight loss if overweight/obese 5

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Common Pitfalls to Avoid

• Failing to start acute treatment early: Effectiveness decreases significantly with delayed initiation 3, 4
• Using high-dose colchicine: No additional benefit and increased gastrointestinal side effects 1
• Not providing prophylaxis when starting ULT: Leads to treatment-induced flares 1
• Stopping ULT during acute flares: Continue ULT once initiated 4
• Using colchicine in severe CKD or with CYP3A4 inhibitors: Risk of fatal toxicity 3, 2
• Starting allopurinol at high doses: Increases risk of adverse effects and flares 1, 6
• Not titrating ULT to target: Subtherapeutic dosing leads to persistent hyperuricemia 1