When is the best time to check uric acid levels and start uric-lowering therapy in a patient with a history of gout?

Optimal Timing for Uric Acid Testing and Initiation of Urate-Lowering Therapy in Gout

Serum uric acid (SUA) should be measured during intercritical periods (between gout attacks) rather than during acute flares, and urate-lowering therapy should be initiated after resolution of acute attacks in patients with recurrent gout (≥2 flares/year), tophi, or radiographic damage.

Timing of Uric Acid Testing

When to Test

• Intercritical period (between attacks): SUA should be measured during symptom-free periods, as SUA levels may be falsely lower during acute attacks 1
• SUA behaves as a negative acute phase reactant, with levels temporarily lowered during episodes of acute inflammation 1
• Studies have shown that SUA levels measured during acute attacks can be within normal range, while the same patients have elevated levels when measured between attacks 1

Why Timing Matters

• Testing during an acute attack may lead to:
  • Underestimation of true uric acid burden
  • Missed diagnosis of hyperuricemia
  • Inadequate dosing of urate-lowering therapy
• The 2020 American College of Rheumatology guidelines recommend regular monitoring of SUA levels every 2-4 weeks during medication titration and every 6 months once target is reached 2

Diagnostic Considerations

• Despite the importance of SUA testing, approximately 40% of patients with a first gout diagnosis by general practitioners have no SUA test result recorded, leading to diagnostic uncertainty 3
• For accurate diagnosis, SUA testing should be combined with clinical features (podagra, tophi, rapid response to colchicine) 2

Initiation of Urate-Lowering Therapy (ULT)

When to Start ULT

The 2020 American College of Rheumatology strongly recommends initiating ULT in patients with:

• Frequent gout flares (≥2 flares per year) 1
• Presence of one or more subcutaneous tophi 1
• Radiographic damage attributable to gout 1

The ACR conditionally recommends initiating ULT in patients with:

• Infrequent flares (<2/year) but with history of more than one flare 1
• First flare with CKD stage ≥3, SUA >9 mg/dL, or urolithiasis 1

When NOT to Start ULT

• For patients with asymptomatic hyperuricemia (SUA >6.8 mg/dL with no prior gout flares or tophi), ULT is conditionally not recommended 1

Approach to ULT Initiation

1. Start after resolution of acute attack

   • Traditionally, ULT was not initiated during acute attacks to avoid prolonging arthritis
   • However, recent evidence suggests that starting allopurinol during an acute attack does not significantly prolong resolution time when appropriate anti-inflammatory prophylaxis is used 4

2. Start with low dose and titrate gradually

   • Begin allopurinol at 100 mg daily 1, 5
   • Increase by 100 mg every 2-4 weeks until target SUA is reached 1
   • Adjust dose in patients with renal impairment 5

3. Provide prophylaxis during initiation

   • Use colchicine or NSAIDs during the first months of ULT to prevent flares 2
   • Continue prophylaxis for more than 8 weeks when initiating ULT 1

4. Monitor SUA regularly

   • Check SUA every 2-4 weeks during dose titration 2
   • Only 48.3% of patients have SUA monitored within six months of therapy initiation, indicating a significant gap in guideline adherence 6

Target SUA Levels

• Maintain SUA below 6 mg/dL (360 μmol/L) for most patients with gout 1, 2
• For patients with severe gout (tophi, frequent attacks, joint damage), target SUA below 5 mg/dL (300 μmol/L) until clinical remission 2
• The goal is to promote crystal dissolution and prevent crystal formation 1

Common Pitfalls to Avoid

1. Testing SUA during acute attacks only

   • May lead to falsely normal or lower values 1
   • Results in underestimation of urate burden

2. Failing to monitor SUA regularly

   • Nearly half of patients don't receive recommended monitoring 6
   • Over half of patients with elevated uric acid levels don't receive appropriate dose adjustments 6

3. Starting with high doses of ULT

   • Increases risk of acute attacks and hypersensitivity reactions 5
   • Start low and titrate gradually

4. Inadequate prophylaxis when initiating ULT

   • Mobilization of urates from tissue deposits during early ULT can trigger acute attacks 5
   • Prophylactic colchicine or NSAIDs are essential

5. Stopping ULT during acute attacks

   • Once established on ULT, it should be continued even during acute attacks 2
   • Fluctuations in SUA levels can trigger more attacks

By following these guidelines for timing of uric acid testing and initiation of urate-lowering therapy, clinicians can optimize gout management and improve long-term outcomes for patients with this common and painful condition.