What are the recommendations for managing chronic gout?

Management of Chronic Gout

Chronic gout management centers on lifelong urate-lowering therapy (ULT) to maintain serum uric acid (SUA) below 6 mg/dL (360 μmol/L), combined with patient education, lifestyle modifications, and management of comorbidities. 1

Patient Education and Lifestyle Modifications

Every patient with chronic gout must receive comprehensive education about the disease pathophysiology, the necessity of lifelong treatment, and the treat-to-target approach. 1 Education significantly improves adherence—one observational study demonstrated 92% treatment success at 12 months when patients received full education. 1

Dietary and Lifestyle Recommendations:

• Weight loss if obese reduces SUA levels (reduction from 570 to 470 μmol/L after 16 weeks in one trial). 1
• Avoid alcohol, especially beer and spirits (RR 1.49 per serving/day for beer; wine does not increase SUA). 1
• Avoid sugar-sweetened drinks and foods rich in fructose, including orange and apple juice. 1
• Limit purine-rich foods: meat and seafood (RR 1.51 for seafood). 1
• Encourage low-fat dairy products (inversely associated with SUA, particularly skimmed milk). 1
• Regular exercise should be advised. 1

Urate-Lowering Therapy (ULT)

Indications for ULT:

ULT should be considered and discussed at first presentation, and is definitively indicated for: 1

• Recurrent acute attacks (≥2 per year)
• Tophi
• Urate arthropathy
• Radiographic changes of gout
• Renal stones
• Young age at presentation (<40 years)
• Very high SUA (>8.0 mg/dL; 480 μmol/L)
• Comorbidities (renal impairment, hypertension, ischemic heart disease, heart failure) 1

Target SUA Levels:

• Standard target: <6 mg/dL (360 μmol/L) for all patients on ULT, maintained lifelong. 1
• Lower target: <5 mg/dL (300 μmol/L) for severe gout (tophi, chronic arthropathy, frequent attacks) until total crystal dissolution. 1
• Avoid SUA <3 mg/dL long-term. 1

First-Line ULT: Allopurinol

In patients with normal kidney function, allopurinol is the first-line ULT. 1

Dosing strategy: 1, 2

• Start at 100 mg daily
• Increase by 100 mg increments every 2-4 weeks until SUA target achieved
• Average effective dose: 200-300 mg/day for mild gout; 400-600 mg/day for moderately severe tophaceous gout 2
• Maximum recommended dose: 800 mg daily 2

In renal impairment: 1

• Adjust maximum allopurinol dose to creatinine clearance 2
• CrCl 10-20 mL/min: maximum 200 mg/day
• CrCl <10 mL/min: maximum 100 mg/day
• CrCl <3 mL/min: lengthen dosing interval 2

Second-Line and Alternative ULT:

If SUA target cannot be reached with appropriate allopurinol dosing: 1

• Switch to febuxostat, OR
• Switch to a uricosuric agent (probenecid, benzbromarone), OR
• Combine allopurinol with a uricosuric

Febuxostat or uricosurics are also indicated if allopurinol cannot be tolerated. 1 Note: Febuxostat is associated with increased all-cause and cardiovascular mortality and is not routinely recommended as first-line. 3

In renal impairment (if allopurinol target not achieved): 1

• Switch to febuxostat, OR
• Use benzbromarone with or without allopurinol (except if eGFR <30 mL/min)

Uricosuric agents (probenecid, sulphinpyrazone): 1

• Alternative to allopurinol in patients with normal renal function
• Relatively contraindicated with urolithiasis
• Benzbromarone can be used in mild-moderate renal insufficiency but carries hepatotoxicity risk 1

Pegloticase:

Reserved for crystal-proven, severe debilitating chronic tophaceous gout with poor quality of life when SUA target cannot be reached with any other available drug at maximal dosage (including combinations). 1

Prophylaxis Against Acute Flares During ULT Initiation

Prophylaxis is recommended during the first 6 months of ULT to prevent acute flares. 1

First-line prophylaxis: 1

• Colchicine 0.5-1 mg/day (reduce dose in renal impairment)
• Monitor for neurotoxicity/muscular toxicity, especially with renal impairment or statin use
• Avoid co-prescription with strong P-glycoprotein and/or CYP3A4 inhibitors (cyclosporin, clarithromycin) 1

If colchicine contraindicated or not tolerated: 1

• Low-dose NSAIDs (if not contraindicated), with gastroprotection if indicated 1

Continue prophylaxis until: 1

• At least 3 months after SUA falls below target in patients without tophi
• At least 6 months in patients with history of tophi 4

Management of Comorbidities

Systematically screen for and address associated comorbidities: 1

• Renal impairment
• Coronary heart disease, heart failure, stroke, peripheral arterial disease
• Obesity
• Hyperlipidemia
• Hypertension
• Diabetes
• Smoking 1

When gout associates with diuretic therapy: 1

• Stop the diuretic if possible 1
• For hypertension: consider losartan (modest uricosuric effect) or calcium channel blockers 1
• For hyperlipidemia: consider fenofibrate (modest uricosuric effect) or statin 1

Treatment of Acute Flares in Chronic Gout Patients

Acute flares should be treated as early as possible; educated patients should self-medicate at first warning symptoms. 1

First-line options: 1

• Colchicine (within 12 hours of flare onset): 1 mg loading dose, then 0.5 mg 1 hour later
• NSAIDs (plus proton pump inhibitor if appropriate)
• Oral corticosteroids (30-35 mg/day prednisolone equivalent for 3-5 days)
• Articular aspiration and corticosteroid injection

Avoid colchicine and NSAIDs in severe renal impairment. 1

For frequent flares with contraindications to colchicine, NSAIDs, and corticosteroids: 1

• Consider IL-1 blockers (contraindicated with current infection)
• Adjust ULT to achieve target following IL-1 blocker treatment 1

Common Pitfalls

• Starting ULT at full dose precipitates acute flares; always start low and titrate slowly 1, 2
• Failing to provide prophylaxis when initiating ULT leads to increased flare frequency 1
• Not treating to target SUA results in continued crystal deposition and disease progression 1
• Discontinuing ULT during acute flares; ULT should be continued once established 1
• Inadequate patient education leads to poor adherence and treatment failure 1