Why is it advised not to discontinue allopurinol once serum uric acid levels are under control?

Why Allopurinol Should Not Be Discontinued After Achieving Target Serum Uric Acid

Allopurinol must be continued indefinitely once serum uric acid levels are controlled because discontinuation leads to recurrence of gout flares in approximately 87% of patients within 5 years, along with potential return of tophi and joint damage. 1

The Evidence for Lifelong Therapy

The 2020 American College of Rheumatology guidelines conditionally recommend continuing urate-lowering therapy (ULT) indefinitely over stopping it, even in patients who achieve clinical remission (no flares for ≥1 year and no tophi). 1

The key data supporting this recommendation comes from a case series where ULT was withheld in patients with years of well-controlled serum urate: 1

• Only 13% of patients (27 of 211) whose serum urate remained <7 mg/dL after stopping therapy had no flares during 5-year follow-up
• This means 87% experienced recurrent gout flares despite previously excellent control
• Patients with higher serum urate concentrations after withholding therapy had more frequent flares
• Higher serum urate levels were directly associated with greater likelihood of flares

The 2016 EULAR guidelines similarly emphasize that approximately 40% of successfully treated patients show recurrence of flares after withdrawal of ULT, reinforcing the need for lifelong therapy. 1

Why Serum Urate Control Requires Continuous Therapy

The fundamental pathophysiology explains why stopping is problematic: 1

• The therapeutic goal is maintaining serum uric acid below the saturation point for monosodium urate crystals (6 mg/dL or 360 μmol/L) 1, 2
• Once therapy stops, serum urate levels rise back above this saturation point
• Crystal formation resumes, leading to renewed deposition in joints and soft tissues
• The uric acid pool that was depleted during treatment begins to rebuild

Patient Perspectives Matter

The ACR Patient Panel specifically voiced strong concerns about: 1

• Return or worsening of gout symptoms
• Recurrence of tophi
• Progressive joint damage with ULT cessation
• If therapy is well-tolerated and not burdensome, patients expressed clear preference to continue treatment indefinitely

The Treat-to-Target Strategy Requires Maintenance

Both ACR and EULAR guidelines strongly recommend a treat-to-target strategy where serum urate is maintained <6 mg/dL lifelong, not just achieved temporarily. 1

• The ACR strongly recommends continuing ULT to achieve and maintain a serum urate target of <6 mg/dL over no target 1
• EULAR states that following complete dissolution of monosodium urate crystals, serum urate should be maintained at <6 mg/dL lifelong 1
• Regular monitoring of serum urate levels is essential because discontinuation predictably leads to loss of control 1

Common Pitfalls to Avoid

The most significant clinical error is discontinuing allopurinol after achieving symptom control. 2, 3

• Symptomatic improvement does not mean the underlying hyperuricemia is permanently resolved
• Gout is a chronic metabolic disorder requiring ongoing management, similar to hypertension or diabetes
• Temporary absence of flares while on therapy does not indicate cure
• Underestimating the need for lifelong therapy based on temporary symptomatic improvement leads to preventable disease recurrence 2

Special Considerations for Dose Adjustment

While discontinuation is not recommended, dose reduction may be considered in specific circumstances: 1, 3

• In patients with severe gout who achieved complete crystal dissolution (resolution of tophi and chronic arthropathy), the dose may be reduced to maintain serum urate <6 mg/dL rather than the more stringent <5 mg/dL target 1, 3
• However, therapy itself should continue indefinitely with regular monitoring every 6 months 2, 3
• If serum urate rises above 6 mg/dL after dose reduction, return to the previous effective dose 3

The Bottom Line

Gout requires lifelong urate-lowering therapy because the underlying metabolic defect causing hyperuricemia persists. Stopping allopurinol after achieving control is analogous to stopping antihypertensive medication after blood pressure normalizes—the disease process remains active and will recur without ongoing treatment. The evidence overwhelmingly demonstrates that discontinuation leads to disease recurrence in the vast majority of patients, making indefinite continuation the standard of care. 1, 2