What is the recommended treatment approach for patients with gout?

Treatment of Gout

For acute gout attacks, initiate treatment within 24 hours with first-line options including NSAIDs at full anti-inflammatory doses, low-dose colchicine (1.2 mg followed by 0.6 mg one hour later), or oral corticosteroids (30-35 mg prednisone equivalent for 3-5 days), and continue any established urate-lowering therapy without interruption during the flare. 1, 2

Acute Gout Attack Management

First-Line Treatment Selection

The single most critical factor for success is early initiation within 24 hours of symptom onset, not which specific agent you choose. 1, 2

Choose based on patient contraindications and joint involvement:

• For patients with normal renal function and no GI/CV contraindications: NSAIDs at full anti-inflammatory doses (naproxen, indomethacin, or any NSAID—no single agent is superior) until complete resolution 1, 2

• For patients with renal impairment, cardiovascular disease, heart failure, or peptic ulcer disease: Oral corticosteroids (prednisone 30-35 mg daily for 3-5 days or 0.5 mg/kg/day for 5-10 days) are the safest option 1, 2

• For monoarticular or oligoarticular flares (1-2 large joints): Intra-articular corticosteroid injection is highly effective and preferred 1, 2

• For patients unable to take oral medications: Parenteral glucocorticoids (IV/IM methylprednisolone 0.5-2.0 mg/kg) are strongly recommended over IL-1 inhibitors or ACTH 1, 2

Colchicine Dosing and Precautions

Use FDA-approved low-dose regimen only: 1.2 mg immediately, followed by 0.6 mg one hour later (maximum 1.8 mg over one hour). 1, 2 High-dose colchicine causes significant GI toxicity with no additional benefit. 1, 2

Critical contraindications for colchicine:

• Avoid completely in patients with severe renal impairment (CrCl <30 mL/min) or those on strong CYP3A4/P-glycoprotein inhibitors (clarithromycin, cyclosporine, ritonavir, atazanavir) due to risk of fatal toxicity 1, 2, 3
• For moderate renal impairment (CrCl 30-50 mL/min), no dose adjustment needed for acute treatment, but monitor closely and do not repeat treatment course more than once every two weeks 3
• For dialysis patients, reduce to single 0.6 mg dose, not to be repeated more than once every two weeks 3

Combination Therapy for Severe Attacks

For severe pain (≥7/10) or polyarticular involvement (≥4 joints): Use combination therapy with colchicine plus NSAIDs, oral corticosteroids plus colchicine, or intra-articular steroids with any other modality. 1, 2

Alternative Agents

IL-1 inhibitors (canakinumab 150 mg subcutaneously or anakinra) are conditionally recommended only for patients with contraindications to all first-line agents and frequent flares. 1, 2 Current infection is an absolute contraindication. 2

Adjunctive Measures

Topical ice application is conditionally recommended as adjuvant therapy during acute attacks. 1, 2

Long-Term Urate-Lowering Therapy (ULT)

Indications to Initiate ULT

Start ULT in patients with:

• Recurrent acute gout attacks (≥2 attacks per year) 1, 2
• Tophaceous gout 1, 2
• Chronic gouty arthropathy 1, 2
• Radiographic changes of gout 1, 2

Do NOT initiate ULT after a first gout attack or in patients with infrequent attacks (<2 per year) without tophi. 1, 2

Target and First-Line Agent

Target serum urate <6 mg/dL to achieve dissolution of monosodium urate crystals. 1, 2

Allopurinol is the preferred first-line agent:

• Start at ≤100 mg/day (lower in renal impairment) 1, 2, 4
• Titrate gradually every 2-5 weeks to reach target serum urate <6 mg/dL 1, 2, 4
• Consider HLA-B*5801 testing before initiating in high-risk populations (Koreans with CKD, Han Chinese, Thai) 4

Alternative agents:

• Febuxostat (another xanthine oxidase inhibitor) if allopurinol not tolerated or ineffective 1, 2
• Uricosuric agents (probenecid, benzbromarone) for patients with normal renal function, no history of urolithiasis, and allopurinol intolerance 1, 2, 4
• Pegloticase is strongly recommended for patients where xanthine oxidase inhibitors, uricosurics, and other interventions have failed and who have frequent flares (≥2/year) or nonresolving tophi 1

Critical Management Principle During ULT Initiation

Continue established ULT without interruption during acute flares—stopping it worsens the flare and complicates long-term management. 1, 2, 5 You may even conditionally start ULT during an acute flare with appropriate anti-inflammatory coverage. 1, 2, 5

Mandatory Anti-Inflammatory Prophylaxis During ULT Initiation

Strongly recommended for ALL patients when starting ULT to prevent treatment-induced flares. 1, 2

First-line prophylactic options:

• Low-dose colchicine (0.5-0.6 mg once or twice daily) 1, 2, 5
• Low-dose NSAIDs with gastroprotection if indicated 1, 2
• Low-dose prednisone (<10 mg/day) 1, 2, 5

Duration of prophylaxis:

• Continue for at least 6 months when initiating ULT 1, 2
• OR continue for 3 months after achieving target serum urate if no tophi present 1, 2, 4
• OR continue for 6 months after achieving target serum urate and tophi have resolved 1, 2, 4
• Continue longer if flares persist despite achieving target 1, 2

Lifestyle Modifications

Strongly recommend:

• Weight loss for obese patients 1, 2, 4
• Avoid alcohol (especially beer and spirits) 1, 2, 5
• Avoid sugar-sweetened beverages and high-fructose corn syrup 1, 2, 5
• Limit purine-rich foods (organ meats, shellfish) 1, 2, 5
• Encourage low-fat or nonfat dairy products and vegetables 1, 2, 5
• Regular exercise 1, 2

Comorbidity Management

Systematically screen all gout patients for:

• Cardiovascular risk factors (hypertension, hyperlipidemia, diabetes) 1, 2
• Renal impairment 1, 2
• Coronary heart disease, heart failure, stroke, peripheral arterial disease 1
• Obesity and smoking 1

Consider losartan for hypertension (increases urinary uric acid excretion) and fenofibrate for hyperlipidemia (reduces serum uric acid). 2

Common Pitfalls to Avoid

• Delaying treatment beyond 24 hours drastically reduces effectiveness 1, 2, 4
• Using high-dose colchicine causes severe GI toxicity with no added benefit 1, 2, 4
• Prescribing colchicine with strong CYP3A4/P-glycoprotein inhibitors can cause fatal toxicity 1, 2, 3
• Stopping ULT during acute flares worsens outcomes 1, 2, 4
• Failing to provide prophylaxis when initiating ULT leads to breakthrough flares and poor adherence 1, 2, 4
• Inadequate duration of prophylaxis (<6 months) increases flare risk 1, 2, 4
• Using NSAIDs in patients with heart failure, peptic ulcer disease, or significant renal disease 2, 4
• Not titrating allopurinol to target serum urate (<6 mg/dL)—using fixed doses is insufficient 1, 2, 4

Patient Education Strategy

Educate patients to self-medicate at first warning symptoms ("pill-in-pocket" approach) to enable treatment within the critical 24-hour window. 1, 2 Fully inform patients about disease pathophysiology, existence of effective treatments, associated comorbidities, and principles of managing acute attacks while maintaining lifelong urate-lowering below target. 1, 2