What is the treatment for an acute gout attack with hyperuricemia?

Treatment for Acute Gout Attack with Hyperuricemia

Immediate Management of the Acute Attack

For an acute gout attack, initiate treatment within 24 hours using NSAIDs, corticosteroids, or low-dose colchicine as first-line options, and do not stop any established urate-lowering therapy during the acute attack. 1

First-Line Treatment Options for Acute Attack

• NSAIDs are the preferred first-line treatment for acute gout attacks, with the most critical factor being early initiation rather than which specific NSAID is chosen 2, 3
• Low-dose colchicine is equally effective as high-dose colchicine for acute attacks but causes significantly fewer gastrointestinal adverse events 1
• Corticosteroids (oral, intravenous, or intra-articular) are appropriate alternatives, particularly in patients with contraindications to NSAIDs or colchicine 2, 1
• Cyclooxygenase-2 inhibitors are associated with fewer total adverse events (38% vs. 60%) and fewer withdrawals due to adverse events (3% vs. 8%) compared to traditional NSAIDs 2

Critical Timing and Continuation of Therapy

• Treatment must be initiated within 24 hours of symptom onset for optimal outcomes 1
• If the patient is already on urate-lowering therapy (such as allopurinol), continue it without interruption during the acute attack 1
• Stopping established urate-lowering therapy during an acute flare can prolong the attack and worsen outcomes 1

Management of Hyperuricemia After the Acute Attack

When to Initiate Urate-Lowering Therapy

• Do not initiate long-term urate-lowering therapy after a first gout attack or in patients with infrequent attacks 1
• For patients with recurrent attacks, discuss benefits, harms, costs, and patient preferences before starting urate-lowering therapy 1
• The goal of urate-lowering therapy is to reduce serum uric acid below 6 mg/dL (360 µmol/L) to prevent future attacks and tophi formation 4, 1, 5

Allopurinol as First-Line Urate-Lowering Therapy

Allopurinol is the first-line urate-lowering therapy, starting at 100 mg daily (or 50 mg daily if eGFR <30 mL/min), with gradual upward titration every 2-5 weeks to achieve target serum uric acid <6 mg/dL. 2, 4, 1, 5

• Start at 100 mg daily for most patients, or 50 mg daily in stage 4 or worse chronic kidney disease 2, 4
• Titrate upward every 2-5 weeks based on serum uric acid levels 2, 4, 1
• The dose can be raised above 300 mg daily, even with renal impairment, provided there is adequate patient education and monitoring for toxicity (rash, pruritus, elevated liver enzymes) 2, 4
• Maximum recommended dose is 800 mg daily 5

Important Safety Considerations for Allopurinol

• Consider HLA-B*5801 testing before initiating allopurinol in high-risk populations: Korean patients with stage 3 or worse CKD, and Han Chinese or Thai patients regardless of renal function 2, 4
• This testing reduces the risk of potentially fatal allopurinol hypersensitivity syndrome 2
• Monitor for signs of toxicity including rash, pruritus, and elevated hepatic transaminases 2, 4

Alternative Urate-Lowering Options

• Febuxostat can be substituted for allopurinol in cases of drug intolerance, adverse events, or failure of upward dose titration 2, 4
• Febuxostat can be used without dose adjustment in mild to moderate renal impairment 4
• Uricosuric agents (probenecid) are not recommended as first-line therapy in patients with creatinine clearance <50 mL/min 2, 4
• Combination therapy with uricosuric agents (fenofibrate or losartan) added to xanthine oxidase inhibitors can be considered in refractory cases 2, 4

Prophylaxis When Initiating Urate-Lowering Therapy

All patients starting urate-lowering therapy require prophylactic anti-inflammatory medication to prevent acute flares during the initial treatment period. 1

• Colchicine (low-dose) or low-dose NSAIDs are appropriate first-line prophylaxis options 1
• Continue prophylaxis for at least 8 weeks, or longer if there is ongoing disease activity or the serum uric acid target has not been reached 1
• Prophylaxis should be maintained until serum uric acid is normalized and the patient has been free from acute attacks for several months 5

Common Pitfalls to Avoid

• Never start allopurinol at standard doses (300 mg) in patients with renal impairment, as this significantly increases toxicity risk 4
• Do not use uricosuric agents as monotherapy in patients with history of kidney stones or elevated urinary uric acid 2, 4
• Do not stop established urate-lowering therapy during an acute attack 1
• Do not delay treatment of the acute attack—initiate within 24 hours 1
• Avoid initiating urate-lowering therapy during an acute attack in treatment-naïve patients; wait until the acute inflammation has resolved 3

Monitoring Strategy

• Monitor serum uric acid levels every 2-5 weeks during dose titration to ensure levels remain below 6 mg/dL 2, 4, 5
• Once stabilized, continue monitoring every 3-6 months long-term 4
• Maintain adequate hydration with daily urinary output of at least 2 liters 5