Treatment Options for Hyperuricemia
The management of hyperuricemia requires a systematic approach combining lifestyle modifications and pharmacologic therapy, with xanthine oxidase inhibitors (XOIs) being the first-line treatment for most patients with persistent hyperuricemia. 1, 2
Initial Assessment
- Perform a thorough clinical evaluation of disease activity through history and physical examination for symptoms of arthritis, presence of tophi, and signs of acute or chronic synovitis 3, 1
- Screen for causes of hyperuricemia, including comorbidities and medications that can elevate uric acid, such as thiazides, loop diuretics, niacin, and calcineurin inhibitors 3
- Consider urine uric acid evaluation for patients with gout onset before age 25 or history of urolithiasis to screen for uric acid overproduction 3, 1
Non-Pharmacologic Management
- Limit consumption of purine-rich meats and seafood to reduce uric acid levels 1, 2
- Avoid high fructose corn syrup sweetened beverages and energy drinks 1, 2
- Encourage consumption of low-fat or non-fat dairy products 2
- Reduce alcohol consumption, particularly beer, and avoid alcohol overuse 2
- Complete abstinence from alcohol during periods of active gout arthritis 2
- Aim for weight reduction if obese 2, 4
Note: 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 2
Pharmacologic Treatment
First-Line Therapy: Xanthine Oxidase Inhibitors
Allopurinol:
- Recommended as the first-line XOI 1, 2
- Start at 100 mg daily and titrate upward every 2-5 weeks to reach target serum urate level 2
- Acts by inhibiting xanthine oxidase, reducing the production of uric acid 5
- Approximately 90% absorbed from the gastrointestinal tract with a plasma half-life of about 1-2 hours 5
- Dose adjustment required in renal impairment: 200 mg daily for creatinine clearance 10-20 mL/min, and no more than 100 mg daily for clearance less than 10 mL/min 5
Febuxostat:
Alternative First-Line Therapy
- Probenecid:
Refractory Disease
- Pegloticase:
Monitoring and Target Levels
- Monitor serum urate every 2-5 weeks during ULT titration and continue measurements every 6 months once target is achieved to monitor adherence 2
- The target serum urate level should be below 6 mg/dL for all gout patients 1, 2
- For patients with greater disease severity and urate burden (tophi, chronic tophaceous gout), target serum urate below 5 mg/dL 2
Special Considerations
Chronic Kidney Disease
- In patients with CKD, xanthine oxidase inhibitors are preferred over uricosuric agents, but dose adjustment is necessary 1, 7
- For acute gout flares in CKD patients, low-dose colchicine or glucocorticoids are preferable to NSAIDs 1
Cardiovascular Disease
- Hyperuricemia is associated with cardiovascular risk factors including dysglycemia, dyslipidemia, central obesity, and abnormal blood pressure 8
- XO inhibitors may provide additional cardiovascular benefits through reduction of oxidative stress and improved endothelial function 8, 9
Common Pitfalls and Caveats
- Poor adherence to ULT is a common problem in gout patients, and regular monitoring helps address this issue 2
- Failure to titrate allopurinol to appropriate doses often leads to suboptimal outcomes, and many patients require doses above 300 mg daily 2
- Initiating ULT at high doses increases risk of adverse events; always start at low doses and titrate upward 2
- Neglecting prophylaxis against acute flares when initiating ULT can lead to poor medication adherence 2
- Bempedoic acid, while primarily used for LDL-cholesterol lowering, may increase serum uric acid and requires monitoring for symptoms of hyperuricemia 3