What is the comparison between Uloric (febuxostat) and allopurinol for treating gout?

Comparison of Uloric (Febuxostat) vs. Allopurinol for Gout Treatment

Allopurinol is strongly recommended as the preferred first-line urate-lowering therapy for gout over febuxostat (Uloric) due to its established efficacy, safety, and lower cost. 1

Key Differences Between Medications

Efficacy

• Serum Urate Lowering:
  • Febuxostat 80mg daily achieves target serum urate (<6 mg/dL) in approximately 70% of patients compared to 38% with allopurinol 300mg daily 2
  • However, when allopurinol is properly dose-titrated (beyond the standard 300mg), it can be equally effective 3

Safety Profile

• Cardiovascular Safety:

  • The CARES trial showed higher all-cause and cardiovascular mortality with febuxostat compared to allopurinol 4
  • However, the more recent FAST trial (2020) demonstrated febuxostat was non-inferior to allopurinol for cardiovascular outcomes 5

• Hypersensitivity Reactions:

  • Allopurinol can cause severe hypersensitivity reactions, particularly in patients with HLA-B*5801 allele 1
  • Febuxostat is not reported to cause severe skin reactions and might have less cross-reactivity than allopurinol in patients with previous reactions 1

Cost Considerations

• Allopurinol is substantially less expensive than febuxostat 1
• The UK's National Institute for Health and Care Excellence (NICE) recommends febuxostat only for patients with contraindications or intolerance to allopurinol 1

Recommended Approach

1. First-line therapy:

   • Start with allopurinol at low dose (≤100mg daily, lower in CKD stage ≥3)
   • Gradually titrate up to achieve target serum urate <6 mg/dL (or <5 mg/dL if tophi present)
   • Allopurinol can be safely titrated above 300mg daily with appropriate monitoring 1

2. Consider febuxostat when:

   • Patient has experienced allopurinol hypersensitivity
   • Patient has failed to achieve target serum urate despite appropriate allopurinol dose titration
   • Patient has moderate-to-severe renal impairment and cannot tolerate allopurinol dose escalation

3. Dosing considerations:

   • Allopurinol: Start at ≤100mg daily (lower in CKD), titrate up gradually
   • Febuxostat: Start at ≤40mg daily, titrate as needed 1

Common Pitfalls to Avoid

1. Inadequate dose titration: Many patients fail therapy because allopurinol is not titrated beyond the standard 300mg daily dose. Up to 97% of patients can achieve target urate levels with proper dose titration 3

2. Lack of flare prophylaxis: Always provide prophylaxis against acute flares when initiating urate-lowering therapy with colchicine (0.5-1mg daily) and/or an NSAID for the first few months 1

3. Discontinuing therapy after flare resolution: Urate-lowering therapy should be continued indefinitely to prevent recurrent flares and complications

4. Ignoring renal function: Start with lower doses in patients with renal impairment but recognize that many patients with CKD will still require dose titration above 300mg daily to achieve target urate levels 1

5. Failing to treat to target: The goal of therapy should be serum urate <6 mg/dL, or <5 mg/dL in patients with tophi 1

In conclusion, while febuxostat may be more potent at standard doses, properly dose-titrated allopurinol remains the preferred first-line agent for most patients with gout due to its established efficacy, safety profile, and lower cost.