What is the recommended treatment plan for an adult with gout, including management of an acute flare and long‑term urate‑lowering therapy?

Gout Treatment

Acute Gout Flare Management

Initiate anti-inflammatory therapy within 24 hours of symptom onset using NSAIDs, low-dose colchicine, or corticosteroids—all three are equally effective, and the choice depends on renal function, cardiovascular risk, gastrointestinal comorbidities, and cost. 1, 2

First-Line Treatment Options

• NSAIDs at full anti-inflammatory doses (e.g., naproxen 500 mg twice daily, indomethacin 50 mg three times daily) should be continued at that dose until the attack completely resolves, typically 5–14 days. 1, 2

• Indomethacin provides no superiority over other NSAIDs in efficacy or safety. 2

• Contraindications to NSAIDs include severe renal impairment (eGFR <30 mL/min), heart failure, cirrhosis, active peptic ulcer disease, or concurrent anticoagulation. 2

• Low-dose colchicine: 1.2 mg at first sign of flare followed by 0.6 mg one hour later (maximum 1.8 mg total). 1, 3

• This low-dose regimen is as effective as higher doses but causes significantly fewer gastrointestinal side effects. 1, 4

• Colchicine must be started within 36 hours of symptom onset; efficacy declines sharply beyond this window. 2

• Absolute contraindication: concomitant use of strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, cyclosporine, ketoconazole, ritonavir, verapamil), especially in patients with renal or hepatic impairment—fatal toxicity has been reported. 2, 3

• Avoid colchicine entirely when creatinine clearance is <30 mL/min. 2

• Corticosteroids are appropriate when NSAIDs or colchicine are contraindicated. 1, 4

• Oral prednisone 30–40 mg daily for 5–10 days (or 2–5 days followed by a 7–10 day taper). 1, 2

• Intramuscular triamcinolone acetonide 60 mg for patients unable to take oral medications. 2

• Intra-articular corticosteroid injection is recommended for mono-articular attacks (e.g., knee 40 mg, ankle 20–30 mg). 1, 2

Combination Therapy for Severe Attacks

• For polyarticular gout (≥4 joints) or severe attacks involving multiple large joints, combine two agents from different classes (e.g., corticosteroid + colchicine or corticosteroid + NSAID). 4, 2
• Never combine NSAIDs with systemic corticosteroids due to synergistic gastrointestinal toxicity. 2

Treatment Response Monitoring

• Goal: ≥20% pain reduction within 24 hours and ≥50% reduction by 48 hours. 1
• If pain improvement is <20% at 24 hours, switch to an alternative monotherapy or add a second agent, and consider alternative diagnoses such as septic arthritis. 1, 2

Critical Management During Acute Flare

• Never discontinue ongoing urate-lowering therapy (allopurinol, febuxostat) during an acute flare; continuation prevents prolongation of symptoms and preserves long-term urate control. 4, 2
• Do not initiate urate-lowering therapy during a first gout attack or any acute flare; initiation should be deferred until after the attack has fully resolved. 1, 4

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Long-Term Urate-Lowering Therapy (ULT)

Indications for Initiating ULT

Start ULT in patients with any of the following: 1, 2

• ≥2 gout attacks per year
• Presence of subcutaneous tophi (clinical or radiographic)
• Radiographic gout damage
• Chronic kidney disease stage ≥3
• Serum urate >9 mg/dL
• History of uric acid kidney stones

Do not initiate ULT after a single gout attack or in patients with <2 attacks per year without other high-risk features. 1, 4

Timing of ULT Initiation

• When ULT is indicated, it should be started during the acute flare rather than waiting for flare resolution—randomized trials show that initiating ULT during a flare does not significantly prolong flare duration or increase severity. 1

First-Line ULT: Allopurinol

• Allopurinol is the preferred first-line agent. 1, 4
• Start with 100 mg daily in patients with normal renal function (50–100 mg in chronic kidney disease). 1, 2, 5
• Titrate upward by 100 mg every 2–5 weeks until serum urate ≤6 mg/dL, not exceeding 800 mg daily. 1, 5
• Renal dosing adjustments: 2, 5
  • CrCl 10–20 mL/min: maximum 200 mg daily
  • CrCl <10 mL/min: maximum 100 mg daily
  • CrCl <3 mL/min: extend dosing interval

Alternative ULT: Febuxostat

• Febuxostat 40 mg daily lowers serum urate as effectively as allopurinol 300 mg daily. 1, 4
• Common adverse effects include abdominal pain, diarrhea, and musculoskeletal pain. 1, 4
• Consider for patients with allopurinol hypersensitivity or inadequate response. 4

Treat-to-Target Strategy

• ULT must be titrated based on serial serum urate measurements to achieve a target <6 mg/dL (360 µmol/L); this approach is strongly superior to fixed-dose regimens. 1, 4
• Monitor serum uric acid every 2–4 weeks during dose titration until target is achieved. 2
• Consider a stricter target <5 mg/dL in the presence of tophi or severe disease. 2

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Mandatory Anti-Inflammatory Prophylaxis During ULT Initiation

All patients starting ULT must receive concomitant anti-inflammatory prophylaxis to prevent gout flares—omission dramatically increases flare risk and leads to treatment abandonment. 1, 4

First-Line Prophylaxis Options

Agent	Typical Dose
Colchicine (low-dose)	0.5–0.6 mg once or twice daily
NSAID (e.g., naproxen)	250 mg twice daily
Corticosteroid (if colchicine/NSAID contraindicated)	Prednisone 5–10 mg daily

1, 2

Duration of Prophylaxis

• Continue prophylaxis for 3–6 months after ULT initiation; stopping before 3 months markedly increases flare risk. 1, 4
• Prophylaxis extending beyond 8 weeks is significantly more effective; flares roughly double when prophylaxis is stopped after only 8 weeks. 6, 1
• Extend prophylaxis beyond 6 months if flares persist or the serum urate target has not yet been reached. 1

Prophylaxis Dose Adjustments

• In patients with creatinine clearance <50 mL/min, reduce colchicine prophylaxis dose to 0.3 mg once daily. 4
• NSAIDs should be avoided in severe renal impairment (creatinine clearance <30 mL/min). 4

Critical Prophylaxis Considerations

• ULT does not reduce gout attacks during the first 6 months and may initially increase flare frequency due to mobilization of urate from tissue deposits. 1
• After 1 year, patients achieving serum urate <6 mg/dL have progressively fewer attacks. 1

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Common Pitfalls to Avoid

• Never initiate ULT without concurrent anti-inflammatory prophylaxis—this dramatically raises flare risk. 1, 4
• Never discontinue prophylaxis before 3 months—premature cessation leads to preventable flares. 1, 4
• Never use a fixed-dose ULT regimen without monitoring and titration—a treat-to-target approach is superior. 1
• Never delay acute flare treatment beyond 24 hours—this significantly compromises effectiveness. 1, 2
• Never start allopurinol at 300 mg daily—this increases the risk of gout flares and hypersensitivity reactions; always start at 100 mg and titrate gradually. 2
• Never use high-dose colchicine regimens (>1.8 mg within the first hour)—they provide no additional benefit and substantially increase gastrointestinal toxicity. 1, 2
• Never stop urate-lowering therapy during acute attacks—this undermines long-term control. 4, 2

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Special Populations

Chronic Kidney Disease

• Allopurinol can be safely dose-escalated in CKD patients, with dose adjustments based on creatinine clearance. 1, 5
• Worse renal function modestly reduces urate-lowering efficacy; larger body size and concomitant diuretic use may necessitate higher allopurinol doses. 1

Hepatic Impairment

• Corticosteroids (oral, intravenous, or intra-articular) are the preferred first-line agents for acute gout when hepatic impairment is present because they are not dependent on hepatic metabolism and have minimal hepatotoxicity risk. 4
• NSAIDs are contraindicated in patients with liver disease due to the risk of hepatotoxicity and acute liver injury. 4
• Colchicine is metabolized by the liver and its toxicity is markedly increased in hepatic dysfunction, making it a relative contraindication. 4

Alcohol Use

• Complete cessation of alcohol, especially beer, is mandatory because alcohol directly precipitates gout attacks and worsens hyperuricemia. 2
• Beer should be eliminated entirely due to its high purine content. 2

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Lifestyle Modifications

• Encourage weight reduction in overweight or obese individuals. 4, 2
• Advise limiting alcohol intake, especially beer and spirits. 4, 2
• Recommend avoiding sugar-sweetened beverages and high-fructose corn syrup. 4, 2
• Suggest reducing consumption of organ meats and shellfish. 4, 2
• Promote intake of low-fat dairy products and a diet rich in vegetables. 4, 2
• Support adequate hydration (target ≥2 L urine output daily). 2