What is the treatment for elevated uric acid in gout?

Treatment of Elevated Uric Acid in Gout

Xanthine oxidase inhibitors (XOIs) such as allopurinol or febuxostat should be the first-line urate-lowering therapy (ULT) for treating elevated uric acid in gout, starting at a low dose and gradually titrating upward to achieve a target serum urate level below 6 mg/dL (or below 5 mg/dL in patients with tophi). 1, 2

Initial Assessment and Treatment Goals

• The treatment target is serum urate below 0.36 mmol/L (6 mg/dL), with the eventual absence of gout attacks and resolution of tophi 2
• For patients with tophi, a more aggressive target of <5 mg/dL (0.30 mmol/L) is recommended 2, 1
• Treatment should be tailored according to:
  • Specific risk factors (serum urate levels, previous attacks, radiographic signs)
  • Clinical phase (acute/recurrent gout, intercritical gout, chronic tophaceous gout)
  • General risk factors (age, sex, obesity, alcohol consumption, medications, comorbidities) 2

Pharmacological Treatment Options

First-Line Therapy: Xanthine Oxidase Inhibitors

1. Allopurinol:

   • Start at 100 mg/day (50 mg/day in patients with stage 4 or worse CKD) 1, 3
   • Increase by 100 mg every 2-5 weeks 1, 3
   • Typical effective dose: 200-300 mg/day for mild gout, 400-600 mg/day for moderate-severe tophaceous gout 3
   • Maximum recommended dose: 800 mg daily 3
   • In patients with renal impairment, start at a lower dose (50-100 mg) and titrate carefully with close monitoring 2, 1

2. Febuxostat:

   • Alternative first-line agent, especially for patients with renal insufficiency or allopurinol intolerance 1
   • Can be used without dose adjustment in mild to moderate renal insufficiency 2, 1

Second-Line Therapy: Uricosuric Agents

1. Probenecid:

   • Consider when XOIs are contraindicated or not tolerated 2, 1
   • Starting dose: 250 mg twice daily for one week, then 500 mg twice daily 4
   • May increase by 500 mg increments every 4 weeks if needed (usually not above 2000 mg/day) 4
   • Not recommended as first-line therapy in patients with creatinine clearance <50 mL/min 2, 1
   • Contraindicated in patients with history of urolithiasis 1

2. Benzbromarone (where available):

   • Alternative uricosuric agent that can be used without dose adjustment in renal impairment 2

Third-Line Therapy

Pegloticase:

• Reserved for patients with severe gout who have failed other treatments 1
• Should only be considered when all other forms of therapy have failed or are contraindicated 2

Prophylaxis During ULT Initiation

• When starting ULT, prophylaxis against acute flares is essential 2
• Options include:
  • Colchicine (preferred): up to 1.2 mg daily 2, 1
  • NSAIDs (if colchicine is contraindicated or not tolerated) 2
  • Low-dose glucocorticoids (if both colchicine and NSAIDs are contraindicated) 2

Non-Pharmacological Approaches

• Advise healthy lifestyle modifications:
  • Weight reduction if obese
  • Regular exercise
  • Smoking cessation
  • Limiting alcohol consumption (especially beer)
  • Avoiding sugar-sweetened drinks 2, 1
• Maintain adequate hydration (at least 2 liters of urine output daily) 1, 3
• Consider urine alkalization with potassium citrate or sodium bicarbonate, especially with uricosuric therapy 1, 4

Monitoring and Follow-Up

• Monitor serum urate levels every 2-5 weeks during dose adjustment 1
• Once target is achieved, check every 6 months 1
• Track frequency of gout attacks and tophi size 2
• Adjust ULT dose as needed to maintain target serum urate level 2, 1

Special Considerations

• Renal Impairment: Allopurinol can be used with careful monitoring and dose adjustment; febuxostat and benzbromarone are alternatives that don't require dose adjustment 2
• Comorbidities: Address associated conditions like hyperlipidemia, hypertension, hyperglycemia, and obesity 2, 1
• Medication Review: Consider eliminating non-essential medications that elevate serum urate (thiazide and loop diuretics, niacin, calcineurin inhibitors) 2, 1

Common Pitfalls to Avoid

1. Failing to titrate ULT to achieve target serum urate levels (only 48.3% of patients have proper monitoring) 5
2. Not providing prophylaxis when initiating ULT, which can lead to flares and treatment discontinuation
3. Discontinuing ULT after symptoms resolve (treatment should be lifelong)
4. Treating asymptomatic hyperuricemia (not recommended to prevent gout, renal disease, or cardiovascular events) 2
5. Using high-dose colchicine for acute attacks (low doses are sufficient and have fewer side effects) 2

Remember that gout is a curable disease with proper treatment, regular monitoring, and patient adherence to both pharmacological and non-pharmacological interventions 6.