What is the best approach to managing gout?

Approach to Gout Management

Gout management requires a dual strategy: aggressive early treatment of acute flares combined with long-term urate-lowering therapy targeting serum uric acid <6 mg/dL, with patient education as the cornerstone of success. 1, 2, 3

Patient Education and Lifestyle Modifications (Foundation of All Management)

Patient education is the single most important intervention, increasing adherence to urate-lowering therapy to 92% at 12 months. 3

• Educate patients to self-medicate acute flares at first warning symptoms ("pill in the pocket" approach) 2, 3
• Weight loss is mandatory for obese patients 1, 2
• Avoid alcoholic drinks, especially beer, and beverages sweetened with high-fructose corn syrup 1, 2, 4
• Reduce intake of purine-rich foods (organ meats, shellfish) 3, 4
• Encourage consumption of vegetables and low-fat or nonfat dairy products 3, 4
• Screen all patients for cardiovascular risk factors and comorbidities (hypertension, hyperlipidemia, hyperglycemia, renal impairment) 3, 1
• Consider losartan for hypertension and fenofibrate for hyperlipidemia, as both reduce serum uric acid 1, 3

Acute Gout Attack Management

Initiate treatment within 12-24 hours of symptom onset for optimal outcomes. 2, 3 Delaying beyond 24 hours significantly reduces effectiveness. 2

First-Line Monotherapy Options (Choose Based on Contraindications):

NSAIDs at full anti-inflammatory doses:

• Any NSAID is acceptable; no single agent is superior 2
• Continue at full dose until attack completely resolves 2
• Avoid in patients with heart failure, peptic ulcer disease, or significant renal disease 2

Low-dose colchicine:

• 1.2 mg at onset, followed by 0.6 mg one hour later 2, 3
• Then 0.5 mg daily 3
• Most effective when started within 12 hours of symptom onset 2
• Adjust dose in moderate to severe chronic kidney disease 2
• Avoid or reduce dose with strong CYP3A4 and P-glycoprotein inhibitors (cyclosporin, clarithromycin, erythromycin) 1, 2, 3

Oral corticosteroids:

• Prednisolone 30-35 mg/day for 3-5 days 2
• Preferred for patients with contraindications to NSAIDs or colchicine 2
• Safest option in renal impairment 2, 3

Intra-articular corticosteroid injection:

• Highly effective for single joint involvement 2
• Preferred for NPO patients with 1-2 affected joints 2

Topical ice application:

• Appropriate as adjunctive measure to pharmacologic therapy 2

Combination Therapy for Severe Presentations:

For severe pain (≥7/10) or polyarticular involvement, use combination therapy: 2

• Colchicine plus NSAIDs, OR
• Oral corticosteroids plus colchicine, OR
• Intra-articular steroids with any other modality

Management of Inadequate Response:

Define inadequate response as <20% improvement in pain within 24 hours or <50% improvement after 24 hours. 2

• Switch to another monotherapy OR add a second recommended agent 2
• For severe refractory attacks, consider IL-1 inhibitors (anakinra or canakinumab), though off-label 2

Continue established urate-lowering therapy without interruption during acute attacks. 2 Discontinuing during flares is a common pitfall. 2

Long-Term Urate-Lowering Therapy (ULT)

Indications for ULT:

Do NOT initiate ULT after a first gout attack or in patients with infrequent attacks. 2

Initiate ULT in patients with: 1, 2, 3

• Recurrent acute attacks (≥2 per year)
• Tophaceous gout (proven or suspected)
• Radiographic changes of gout
• Chronic kidney disease stage ≥2 with hyperuricemia

Target Serum Uric Acid:

Target serum uric acid <6 mg/dL at minimum, often <5 mg/dL for patients with tophi or severe disease. 1, 2, 3

First-Line ULT: Xanthine Oxidase Inhibitors

Allopurinol is the preferred first-line agent, including for patients with moderate-to-severe chronic kidney disease: 1, 3, 5

• Start at ≤100 mg/day (lower in moderate to severe CKD) 1, 5
• Titrate gradually every 2-5 weeks by 100 mg increments 1, 5
• Titrate to achieve target serum uric acid <6 mg/dL, NOT to a standard dose 1, 2
• Maintenance dose can exceed 300 mg daily, even in patients with CKD 1
• Maximum recommended dose is 800 mg daily 5
• For creatinine clearance 10-20 mL/min: 200 mg daily maximum 5
• For creatinine clearance <10 mL/min: 100 mg daily maximum 5

HLA-B*5801 screening before allopurinol initiation: 1

• Mandatory for Koreans with stage 3 or worse CKD, and all Han Chinese and Thai descent patients 1
• These populations have elevated allele frequency and very high hazard ratio for severe allopurinol hypersensitivity syndrome

Febuxostat as alternative xanthine oxidase inhibitor: 1

• Appropriate for patients with contraindications or intolerance to allopurinol 1
• Can be prescribed at unchanged doses for mild-to-moderate renal or hepatic impairment 6

Second-Line ULT: Uricosuric Agents

Uricosuric agents (probenecid, benzbromarone) are alternatives in patients with: 1, 3

• Normal renal function
• No history of urolithiasis
• Allopurinol intolerance or contraindication

Combination oral ULT (one xanthine oxidase inhibitor + one uricosuric agent) is appropriate when serum urate target has not been met by appropriate dosing of a xanthine oxidase inhibitor alone. 1

Third-Line ULT: Pegloticase

Pegloticase is appropriate for patients with severe gout disease burden and refractoriness to, or intolerance of, appropriately dosed oral ULT therapy options. 1, 3, 7

• Discontinue oral urate-lowering medications before starting pegloticase 7
• Monitor serum uric acid levels prior to each infusion; consider discontinuing if levels increase to >6 mg/dL 7
• Must be administered in healthcare setting prepared to manage infusion reactions 7
• Pre-treat with antihistamines and corticosteroids 7
• Infuse slowly over no less than 120 minutes 7

Anti-Inflammatory Prophylaxis During ULT Initiation

Prophylaxis is mandatory when starting urate-lowering therapy to prevent flares. 1, 2, 3

First-line prophylaxis options: 1, 2, 3

• Low-dose colchicine 0.5-1 mg daily (preferred)
• Low-dose NSAIDs with gastroprotection
• Low-dose prednisone

Duration of prophylaxis: 1, 2, 3

• At least 6 months, OR
• 3 months after achieving target serum urate if no tophi are present, OR
• 6 months after achieving target serum urate if tophi are present

Inadequate duration of prophylaxis leads to breakthrough flares and poor medication adherence. 2 This is a common pitfall.

Special Considerations

Diuretic-associated gout: 3

• Substitute the diuretic if possible
• Consider losartan or calcium channel blockers for hypertension

Tophaceous gout: 3

• Treat medically by achieving sustained serum uric acid reduction, preferably <5 mg/dL
• Surgical debridement rarely indicated

Asymptomatic hyperuricemia: 3

• Do NOT treat with urate-lowering therapy

Common Pitfalls to Avoid

• High-dose colchicine regimens cause significant gastrointestinal side effects with no additional benefit over low-dose regimens 2, 3
• Discontinuing urate-lowering therapy during acute flares reduces long-term success 2
• Using standard allopurinol doses (300 mg) without titrating to target serum uric acid 1, 2
• Failing to provide adequate prophylaxis duration when initiating urate-lowering therapy 2
• Delaying acute attack treatment beyond 24 hours 2
• Ignoring drug interactions, particularly with colchicine 1, 2