What is the treatment protocol for hyperuricemia?

Hyperuricemia Treatment Protocol

The first-line pharmacologic treatment for hyperuricemia in gout is a xanthine oxidase inhibitor (XOI), specifically allopurinol or febuxostat, with the goal of achieving serum urate levels below 6 mg/dL (or below 5 mg/dL in patients with tophi or chronic tophaceous gout). 1

Initial Assessment and Non-Pharmacologic Approaches

• Perform thorough clinical evaluation of gout disease activity and burden through history and physical examination for symptoms of arthritis, presence of tophi, and signs of acute or chronic synovitis 1
• Screen for causes of hyperuricemia including comorbidities (obesity, hypertension, diabetes, hyperlipidemia) and medications that can elevate uric acid (thiazides, loop diuretics, niacin, calcineurin inhibitors) 1
• Consider urine uric acid evaluation for patients with gout onset before age 25 or history of urolithiasis to screen for uric acid overproduction 1

Lifestyle Modifications

• Limit consumption of purine-rich meats and seafood 1
• Avoid high fructose corn syrup sweetened beverages and energy drinks 1
• Encourage consumption of low-fat or non-fat dairy products 1
• Reduce alcohol consumption, particularly beer, and avoid alcohol overuse 1
• Complete abstinence from alcohol during periods of active gout arthritis 1
• Maintain adequate hydration with daily urinary output of at least 2 liters 2
• Aim for weight reduction if obese 1

Pharmacologic Treatment

Indications for Urate-Lowering Therapy (ULT)

• Recurrent gout attacks (≥2 per year) 1
• Presence of tophi on physical examination 1
• Chronic kidney disease stage 2-5 or end-stage renal disease with prior gout attacks and current hyperuricemia 1
• Evidence of destructive gout 1

First-Line ULT

• Xanthine oxidase inhibitors (XOIs) are recommended as first-line therapy 1
  • Allopurinol: Start at 100 mg daily (50 mg daily in patients with stage 4 or worse CKD) 1
  • Titrate dose upward every 2-5 weeks to reach target serum urate level 1
  • Maximum dose can exceed 300 mg daily with appropriate monitoring 1
  • Consider HLA-B*5801 screening in high-risk populations (Koreans with stage 3 or worse CKD, and all those of Han Chinese and Thai descent) before initiating allopurinol 1
  • Febuxostat: Alternative XOI with similar efficacy 1

Alternative ULT

• Probenecid: Recommended as an alternative first-line therapy when XOIs are contraindicated or not tolerated 1
• Not recommended as first-line monotherapy in patients with creatinine clearance below 50 mL/min 1
• Pegloticase: Reserved for patients with refractory disease who have failed maximum appropriate doses of XOI and uricosuric combination therapy 1

Dosing Considerations

• Adjust allopurinol dose based on renal function 2:
  • Creatinine clearance 10-20 mL/min: 200 mg daily
  • Creatinine clearance <10 mL/min: ≤100 mg daily
  • Extreme renal impairment (clearance <3 mL/min): Extend interval between doses
• ULT can be started during an acute gout attack if effective anti-inflammatory management has been instituted 1

Monitoring and Target Levels

• Monitor serum urate every 2-5 weeks during ULT titration 1
• Continue measurements every 6 months once target is achieved to monitor adherence 1
• Target serum urate level should be below 6 mg/dL for all gout patients 1
• For patients with greater disease severity and urate burden (tophi, chronic tophaceous gout), target serum urate below 5 mg/dL 1

Treatment of Asymptomatic Hyperuricemia

• Pharmacologic treatment of asymptomatic hyperuricemia is not recommended to prevent gouty arthritis, renal disease, or cardiovascular events 1
• Focus on lifestyle modifications and addressing underlying comorbidities 1

Special Considerations

• In patients with chronic kidney disease, xanthine oxidase inhibitors are preferred over uricosuric agents 1
• For acute gout flares in CKD patients, low-dose colchicine or intra-articular/oral glucocorticoids are preferable to NSAIDs 1
• Diet and lifestyle measures alone typically provide only 10-18% decrease in serum urate, which is insufficient for most patients with sustained hyperuricemia above 7 mg/dL 1

Common Pitfalls and Caveats

• Poor adherence to ULT is a common problem in gout patients; regular monitoring helps address this issue 1
• Failure to titrate allopurinol to appropriate doses often leads to suboptimal outcomes; many patients require doses above 300 mg daily 1
• Initiating ULT at high doses increases risk of adverse events; always start at low doses and titrate upward 1
• Neglecting prophylaxis against acute flares when initiating ULT can lead to poor medication adherence 1
• Diet alone is typically insufficient for adequate urate lowering in most gout patients 1