What is the recommended management and treatment for gout?

Management and Treatment of Gout

Acute Gout Flare Treatment

For acute gout attacks, initiate treatment immediately with colchicine, NSAIDs, or oral corticosteroids—all three are equally effective first-line options, and the choice depends on patient comorbidities and contraindications rather than efficacy differences. 1, 2, 3

First-Line Agent Selection

• Colchicine is most effective when started within 12 hours of symptom onset, using low-dose regimen: 1.2 mg (two 0.6 mg tablets) at first sign, followed by 0.6 mg one hour later, with maximum 1.8 mg in first 24 hours 1, 2, 3

  • Low-dose colchicine has similar efficacy to high-dose but significantly fewer adverse effects 3
  • Critical contraindication: Avoid in severe renal impairment (CrCl <30 mL/min) or patients on strong CYP3A4/P-glycoprotein inhibitors (clarithromycin, ritonavir, ketoconazole) due to risk of fatal toxicity 3, 4

• NSAIDs at full anti-inflammatory doses are equally effective, with no clinically significant differences between agents 2, 3

  • Add proton pump inhibitor if gastrointestinal risk factors present 1, 2
  • Contraindications: Active peptic ulcer disease, severe renal failure (CrCl <30 mL/min), uncontrolled hypertension, heart failure 3

• Oral corticosteroids (prednisone or prednisolone 30-35 mg daily for 3-5 days) are the safest option for patients with renal impairment, cardiovascular disease, or gastrointestinal contraindications to NSAIDs 2, 3

  • Particularly effective for polyarticular flares with systemic inflammation 3

Special Situations

• Monoarticular or oligoarticular flares (1-2 large joints): Intra-articular corticosteroid injection is highly effective and preferred 3

• Patients unable to take oral medications: Use parenteral glucocorticoids (intramuscular or intravenous) over IL-1 inhibitors 3

• Severe polyarticular attacks: Combination therapy with full doses of two agents (e.g., colchicine + NSAIDs, oral corticosteroids + colchicine, or intra-articular steroids with any other modality) is appropriate 1

• IL-1 inhibitors (canakinumab 150 mg subcutaneously): Reserved only for patients with contraindications to all first-line agents and frequent flares; absolute contraindication if active infection present 3

Urate-Lowering Therapy (ULT)

Indications for Initiating ULT

Strongly indicated for: 1, 2

• Tophaceous gout (any tophi on physical exam)
• Radiographic damage due to gout
• Frequent gout flares (≥2 attacks per year)
• Chronic kidney disease stage ≥2
• History of urolithiasis

Consider early initiation if: 2

• Young age (<40 years) with very high serum urate (>8 mg/dL)
• First attack with significant comorbidities

Do not initiate after first attack or in patients with infrequent attacks (<2 per year without tophi or joint damage) 2

First-Line ULT: Allopurinol

Allopurinol is the preferred first-line urate-lowering therapy for all patients, including those with moderate-to-severe chronic kidney disease (stage ≥3). 1, 2

• Starting dose: ≤100 mg/day (lower in CKD: 50 mg/day if CrCl 10-20 mL/min; 50-100 mg/day if CrCl 30-50 mL/min) 1, 4
• Titration: Increase by 50-100 mg every 2-4 weeks based on serum urate levels 1, 2
• Target serum urate: <6 mg/dL (360 μmol/L) for all patients; consider <5 mg/dL (300 μmol/L) for patients with tophi to facilitate faster resolution 1

Alternative ULT Agents

• Febuxostat: Second-line xanthine oxidase inhibitor; start at <40 mg/day and titrate to achieve target 1

  • Can be used without dose adjustment in mild-to-moderate renal impairment 1

• Uricosuric agents (probenecid, benzbromarone): Consider for patients who cannot tolerate xanthine oxidase inhibitors 1

  • Contraindicated in patients with urolithiasis or uric acid overproduction 5

• Pegloticase (uricase): Reserved only for severe refractory gout where all other therapies have failed or are contraindicated 1

Critical ULT Management Principles

Continue ULT without interruption during acute flares—stopping therapy worsens the flare and complicates long-term management. 2, 3

ULT can be started during an acute flare; there is no need to wait for flare resolution. 2, 3

Anti-Inflammatory Prophylaxis During ULT Initiation

When initiating or uptitrating ULT, concomitant anti-inflammatory prophylaxis is mandatory for minimum 3-6 months to prevent treatment-induced flares. 1, 2

Prophylaxis Agent Selection

• First-line: Low-dose colchicine 0.5-0.6 mg once or twice daily 1, 3

  • Dose adjustment required in renal impairment: 0.3 mg daily if CrCl <50 mL/min; 0.3 mg twice weekly if on dialysis 4

• Second-line: Low-dose NSAIDs (e.g., naproxen 250 mg twice daily) with PPI if indicated 1

• Third-line: Low-dose prednisone or prednisolone (<10 mg/day) if colchicine and NSAIDs contraindicated, not tolerated, or ineffective 1

Duration of Prophylaxis

Continue prophylaxis for the greater of: 1

• Minimum 6 months, OR
• 3 months after achieving target serum urate in patients without tophi, OR
• 6 months after achieving target serum urate in patients with history of tophi

Extend prophylaxis beyond 6 months if gout attacks continue to occur. 2, 3

Lifestyle Modifications

All patients should receive education on lifestyle modifications: 1, 2

• Weight loss if overweight or obese
• Avoid alcohol, especially beer and spirits
• Eliminate sugar-sweetened beverages and foods high in fructose
• Reduce excessive consumption of red meat and seafood
• Promote low-fat dairy products
• Regular exercise

Monitoring and Follow-Up

• Serum urate levels: Monitor regularly during ULT titration (every 2-4 weeks initially, then every 6 months once at target) 1, 2
• Frequency of gout attacks: Track to assess treatment effectiveness 1
• Renal function and cardiovascular risk factors: Assess at baseline and monitor periodically 1, 2
• Tophi size: Document and monitor for resolution 1

Critical Pitfalls to Avoid

• Delaying treatment of acute flare: Early initiation is the single most important determinant of success, not which agent is chosen 3, 5
• Using colchicine with CYP3A4/P-gp inhibitors or in severe renal impairment: Can result in fatal toxicity 3, 4
• Stopping ULT during acute flare: Worsens the flare and complicates management 2, 3
• Starting allopurinol at high doses: Increases risk of hypersensitivity reactions and precipitates flares 1
• Failing to provide prophylaxis when initiating ULT: Results in treatment-induced flares and poor adherence 1, 2
• Not treating to target serum urate: Subtherapeutic dosing leads to continued flares and disease progression 1