When should urate‑lowering therapy be started in a patient with documented hyperuricemia (>6 mg/dL) and gout who is currently not in an acute flare?

When to Start Urate-Lowering Therapy in Gout Patients Not in Flare

Urate-lowering therapy (ULT) should be initiated immediately in any patient with documented gout who has ≥2 flares per year, any subcutaneous tophi, or radiographic joint damage—regardless of whether they are currently in a flare. 1

Strong (Absolute) Indications – Start ULT Now

These patients require immediate ULT initiation regardless of current flare status or serum urate level:

• Frequent gout flares (≥2 per year) – The American College of Rheumatology strongly recommends starting allopurinol for recurrent disease. 1

• Presence of any subcutaneous tophi – Even a single tophus identified on physical exam or imaging mandates treatment. 1, 2

• Radiographic damage attributable to gout – Joint damage on any imaging modality (X-ray, ultrasound, CT, MRI) is an absolute indication. 1, 2

• Chronic tophaceous gouty arthropathy – Persistent joint symptoms from synovitis or articular tophi require immediate therapy. 2

• History of uric acid kidney stones (urolithiasis) – Both the European League Against Rheumatism and American College of Rheumatology identify this as an indication for ULT. 1, 2

Conditional Indications – Strongly Consider Starting ULT

For patients with >1 previous flare but infrequent attacks (<2/year), the American College of Rheumatology conditionally recommends starting ULT. 1

For patients experiencing their first gout flare, consider initiating ULT if any of these high-risk features are present:

• Chronic kidney disease stage ≥3 (eGFR <60 mL/min/1.73 m²) – Renal impairment increases risk of progressive disease. 1, 2

• Serum urate >9 mg/dL – This level indicates higher likelihood of gout progression and clinical tophi development. 1, 2

• Young age (<40 years) – The European League Against Rheumatism recommends initiating ULT close to the time of first diagnosis in younger patients. 1

• Significant cardiovascular comorbidities – Hypertension, ischemic heart disease, or heart failure support earlier initiation. 2

When NOT to Start ULT

Asymptomatic hyperuricemia alone (elevated uric acid without any gout symptoms or crystal-proven disease) is NOT an indication for ULT. 2 The American College of Rheumatology conditionally recommends against initiating ULT for asymptomatic hyperuricemia, even at levels >9 mg/dL, because the number needed to treat is high (24 patients for 3 years to prevent a single gout flare) and only 20% of patients with urate >9 mg/dL develop gout within 5 years. 2

Initiation Protocol When Starting ULT

Step 1: Start Allopurinol at Low Dose

• 100 mg daily for patients with normal renal function 1, 3
• 50 mg daily for patients with CKD stage ≥4 1, 3

Step 2: Mandatory Flare Prophylaxis

Colchicine 0.5–1 mg daily for at least 6 months is strongly recommended when initiating allopurinol to prevent flares triggered by rapid urate lowering. 1, 3 Lack of prophylaxis when starting ULT increases the odds of early flare recurrence by more than 11-fold. 4

Alternative prophylaxis if colchicine is contraindicated:

• Low-dose NSAIDs (with dose reduction in renal impairment) 1
• Low-dose prednisone (<10 mg/day) 1

Prophylaxis for less than 3 months yields significantly less benefit than a 6-month course, and flare rates increase sharply when prophylaxis is stopped at 8 weeks. 1, 5

Step 3: Titrate to Target

• Increase allopurinol by 100 mg every 2–5 weeks based on serum urate measurements 1, 3
• Target serum urate <6 mg/dL for all patients 1, 2
• Target <5 mg/dL for severe gout with tophi, chronic arthropathy, or frequent attacks—maintain this lower target until resolution, then maintain <6 mg/dL 1, 2
• Most patients require doses >300 mg daily to reach target; the maximum FDA-approved dose is 800 mg daily 1, 3

Step 4: Monitor Serum Urate

• Every 2–5 weeks during dose titration until target is achieved 1, 2
• Every 6 months after reaching target to assess adherence and maintain control 1, 2

Timing Relative to Acute Flares

You do NOT need to wait for a flare to resolve before starting ULT. The 2020 American College of Rheumatology guidelines conditionally recommend starting ULT during an acute gout flare rather than waiting, because:

• Two randomized controlled trials showed that starting allopurinol during an acute attack does not prolong flare duration or increase severity 1, 6
• Patients experiencing acute symptoms are highly motivated to start preventive therapy 1
• Initiating therapy during the flare visit prevents loss to follow-up 1

If you do start during a flare, treat the acute attack separately with therapeutic doses of NSAIDs, colchicine, or corticosteroids, while simultaneously beginning low-dose allopurinol with prophylaxis. 1

Critical Pitfalls to Avoid

• Never start allopurinol at 300 mg daily – this increases flare risk and hypersensitivity reactions; always start low and titrate. 1, 3

• Never omit prophylaxis – lack of prophylaxis dramatically increases flare risk in the first 3–6 months and is a major cause of treatment failure and non-adherence. 1, 4

• Never accept serum urate ≥6 mg/dL as adequate – persistent hyperuricemia above 6.8 mg/dL (the saturation point) promotes ongoing crystal formation and disease progression. 1, 7

• Never stop ULT during an acute flare – continue the current dose and add anti-inflammatory treatment; stopping causes urate fluctuations that can trigger additional flares. 1

• Do not delay ULT in patients with strong indications – waiting for "the right time" in patients with tophi, frequent flares, or joint damage allows irreversible damage to progress. 1, 2