When to Start Urate-Lowering Therapy in Gout
Patients with frequent gout flares (≥2 per year), subcutaneous tophi, or radiographic joint damage should strongly start urate-lowering therapy immediately. 1, 2
Strong Indications (Start ULT Now)
The following conditions mandate initiation of urate-lowering therapy:
Frequent gout flares (≥2 attacks per year) - This represents the clearest indication for ULT, with high-certainty evidence showing substantial benefit in preventing future attacks and disease progression 1, 2
Presence of one or more subcutaneous tophi - Even a single tophus mandates treatment, as this indicates advanced disease with tissue urate deposition 1, 2
Radiographic damage attributable to gout - Any imaging modality showing joint damage from gout (erosions, joint space narrowing, urate arthropathy) requires ULT initiation 1, 2
History of kidney stones (urolithiasis) - Both allopurinol and febuxostat lower 24-hour urinary uric acid excretion and reduce stone recurrence 1, 2
Conditional Indications (Consider Starting ULT)
For patients with infrequent flares (<2 per year) but more than one previous attack, conditionally recommend starting ULT, as moderate-certainty evidence shows 30% versus 41% subsequent flare rates with treatment versus placebo 1, 2
For patients experiencing their first gout flare, generally recommend against starting ULT unless any of these high-risk features are present 1, 2:
Chronic kidney disease stage ≥3 - Higher likelihood of gout progression, development of tophi, and limited treatment options for acute flares make early ULT beneficial 1, 2
Serum urate >9 mg/dL - Markedly elevated levels predict gout progression and warrant earlier intervention 1, 2
Young age (<40 years) - Earlier disease onset suggests more aggressive course requiring earlier ULT 2
Significant comorbidities - Renal impairment, hypertension, ischemic heart disease, or heart failure increase the risk-benefit ratio favoring ULT 2
When NOT to Start ULT
Asymptomatic hyperuricemia (serum urate >6.8 mg/dL with no prior gout flares or tophi) should NOT be treated with ULT. 1, 3, 4 The FDA label explicitly states allopurinol "is not recommended for the treatment of asymptomatic hyperuricemia" and "is not an innocuous drug." 4 The number needed to treat is prohibitively high: 24 patients would need treatment for 3 years to prevent a single incident gout flare, and only 20% of patients with serum urate >9 mg/dL develop gout within 5 years. 1, 3
Critical Implementation Points
When initiating ULT, always provide anti-inflammatory prophylaxis with colchicine 0.5-1 mg/day for at least 6 months to prevent flares triggered by rapid urate lowering 1, 2. If colchicine is contraindicated, use low-dose NSAIDs or low-dose glucocorticoids. 2
Start allopurinol at low doses (100 mg/day in normal renal function, 50 mg/day in CKD stage ≥4) and titrate upward by 100 mg every 2-5 weeks until serum urate reaches <6 mg/dL 1, 2. Most patients require doses >300 mg/day to achieve target, and doses up to 800 mg/day are FDA-approved. 2
ULT can be started during an acute gout flare rather than waiting for resolution - this is conditionally recommended to avoid delayed therapy and ensure treatment adherence 2. Continue any existing ULT during acute flares without interruption. 2
Common Pitfalls to Avoid
Undertreating with fixed 300 mg allopurinol doses - Most patients need higher doses titrated to achieve serum urate <6 mg/dL 2
Stopping prophylaxis too early - Discontinuing before 6 months increases breakthrough flare risk 2
Treating asymptomatic hyperuricemia - This provides minimal benefit with potential medication risks and costs 1, 3, 4
Delaying ULT in patients with tophi or frequent flares - These patients have strong indications and should start immediately 1, 2