What are the uric acid lowering strategies for a patient after the first acute gout (Gouty Arthritis) attack?

From the Guidelines

After a first gout attack, the American College of Physicians recommends against initiating long-term urate-lowering therapy in most patients, as the benefits of long-term use have not been studied in patients with a single or infrequent gout attacks 1. Instead, focus on lifestyle modifications such as:

• Limiting purine-rich foods like red meat, organ meats, seafood, and alcohol (especially beer)
• Increasing water intake to at least 2-3 liters daily to help flush uric acid through the kidneys
• Maintaining a healthy weight through gradual weight loss if overweight, as rapid weight loss can trigger attacks
• Encouraging low-fat dairy products and regular exercise

For patients with recurrent gout attacks, urate-lowering therapy should be considered and discussed with the patient, taking into account the benefits, harms, costs, and individual preferences 1. Allopurinol is typically started at 100mg daily and gradually increased to achieve a target uric acid level below 6 mg/dL. Febuxostat (40-80mg daily) is an alternative for those who cannot tolerate allopurinol. During the first few months of uric acid-lowering therapy, prophylactic colchicine (0.6mg once or twice daily) or low-dose NSAIDs may be prescribed to prevent flares that can occur as uric acid levels change. Regular monitoring of uric acid levels is essential to ensure the treatment is effective.

Key points to consider:

• The patient's individual preferences and values should be taken into account when making decisions about urate-lowering therapy
• The benefits and harms of urate-lowering therapy should be carefully weighed, particularly in patients with infrequent gout attacks
• Lifestyle modifications should be encouraged in all patients with gout, regardless of whether urate-lowering therapy is initiated.

From the FDA Drug Label

The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.

Uric Acid Lowering Tips:

• Start with a low dose of allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained
• Maintain a fluid intake sufficient to yield a daily urinary output of at least 2 liters
• Maintain a neutral or, preferably, slightly alkaline urine
• Monitor serum uric acid levels to determine the correct size and frequency of dosage for maintaining the serum uric acid just within the normal range 2

From the Research

Uric Acid Lowering Tips for a Patient after 1st Gout Attack

• The goal of uric acid lowering therapy is to prevent gout flares and reduce serum uric acid levels 3, 4
• First-line agents for urate lowering therapy include allopurinol and febuxostat 3, 4, 5
• Allopurinol is an agent of first choice for urate lowering therapy, but screening for HLA*B58:01 mutation is recommended in Southeast Asian and Black populations to decrease the occurrence of allopurinol hypersensitivity syndrome 3
• Febuxostat is another efficacious urate lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety 3, 4
• Uricosuric agents, such as probenecid, sulfinpyrazone, and benzbromarone, can be used as adjuncts to urate lowering therapy 4, 5
• Lifestyle modifications, such as diet and exercise, can also help lower uric acid levels and prevent gout flares 3, 4

Medication Adherence and Persistence

• Long-term persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy among patients with gout was suboptimal, with allopurinol having worse persistence rates than febuxostat 6
• Poor health literacy was the most common reason for XOI withdrawal 6
• Patients with gout with tophi and shorter symptom duration were found to be at high risk for poor persistence of XOIs 6

Emerging Therapies

• Novel uricosurics, such as verinurad and arhalofenate, are a class for continued drug development and may offer future promise for urate lowering therapy 3
• Pegloticase is effective for patients with recalcitrant gout, but its immunogenicity significantly threatens the achievement of sustained urate lowering responses 3