When can urate lowering therapy (ULT) be stopped in patients with a history of gout?

When to Stop Urate-Lowering Therapy in Gout

Urate-lowering therapy (ULT) should generally be maintained lifelong and not discontinued in patients with a history of gout, as current guidelines explicitly recommend maintaining serum urate <6 mg/dL indefinitely. 1

Guideline-Based Recommendations

Standard Approach: Lifelong Therapy

• The EULAR guidelines explicitly state that serum urate <6 mg/dL (360 μmol/L) should be maintained lifelong once ULT is initiated. 1

• This recommendation applies to all patients who meet criteria for ULT initiation, including those with:

  • Recurrent flares (≥2/year) 1
  • Subcutaneous tophi 1
  • Radiographic damage attributable to gout 1
  • Chronic kidney disease stage ≥3 with serum urate >9 mg/dL 1, 2

Limited Evidence for Discontinuation

• The American College of Physicians acknowledges that insufficient evidence suggests some patients with annual urate levels <7 mg/dL (<416 μmol/L) may be able to stop ULT after approximately 5 years, but this remains an area of inconclusive evidence. 1

• This represents the only guideline-level suggestion for potential discontinuation, and it is explicitly labeled as having insufficient supporting evidence. 1

Research Evidence on Discontinuation Outcomes

High Relapse Rates After Stopping ULT

• A systematic review found that gout relapse rates after ULT discontinuation ranged from 36-81%, with relapses typically occurring 1-4.5 years after stopping therapy. 3

• Relapse rates were substantially lower (15%) in patients with urolithiasis compared to those with gouty arthritis. 3

Protective Factors Against Relapse

• Low serum urate levels both before and after ULT discontinuation were associated with lower gout recurrence rates in observational studies. 3

• However, the quality of existing discontinuation studies is poor (MINORS scores 5-10 out of 16), limiting the strength of these conclusions. 3

Clinical Algorithm for Decision-Making

Patients Who Should Never Discontinue ULT

Continue ULT indefinitely in patients with:

• Persistent tophi (even if reduced in size) 1
• Radiographic joint damage from gout 1
• History of frequent flares (≥2/year) prior to ULT 1
• Chronic kidney disease stage ≥3 1, 2
• History of urolithiasis 1, 2

Patients Where Discontinuation Might Be Considered (With Extreme Caution)

Only consider discontinuation in highly selected patients meeting ALL of the following criteria:

• At least 5 years of continuous ULT 1
• Serum urate consistently <6 mg/dL (ideally <5 mg/dL) for the entire treatment period 1, 3
• Complete resolution of tophi (if previously present) 1
• No gout flares for at least 2-3 years 3
• No radiographic damage 1
• Normal kidney function 1
• Patient understands the 36-81% risk of relapse 3

Monitoring After Discontinuation (If Attempted)

If discontinuation is attempted despite the above caveats:

• Monitor serum urate every 3 months for the first year, then every 6 months thereafter 1
• Immediately restart ULT if serum urate rises above 6 mg/dL 1
• Restart ULT at first sign of gout flare recurrence 3
• Counsel patients that relapse may occur 1-4.5 years after stopping 3

Critical Pitfalls to Avoid

Common Errors in Clinical Practice

• Stopping ULT during acute flares: ULT should be continued during acute gout attacks, with anti-inflammatory therapy added for flare management. 1, 2

• Discontinuing ULT after achieving target urate: Achieving target urate does not eliminate the underlying hyperuricemia; crystal dissolution continues for months to years, and stopping therapy allows re-accumulation. 1

• Assuming dialysis eliminates need for ULT: Recent evidence shows ULT remains protective against gout flares even in hemodialysis patients (50% flare rate without ULT vs. 22.68% with ULT). 4

Medication-Specific Considerations

• Allopurinol and febuxostat discontinuation both carry similar relapse risks, as the underlying hyperuricemia persists regardless of the mechanism of ULT. 3

• Patients on diuretics who discontinue ULT face particularly high relapse risk due to the urate-elevating effects of these medications. 1

Quality of Life and Mortality Considerations

• Uncontrolled gout is associated with increased cardiovascular mortality and global excess mortality, particularly in patients with comorbidities like chronic kidney disease, diabetes, and heart failure. 5, 4

• Progressive joint damage from recurrent flares significantly impairs quality of life and can lead to chronic tophaceous gout with permanent disability. 2, 5

• The morbidity from gout relapse after ULT discontinuation outweighs the minimal risks of continuing long-term ULT in most patients. 3, 5