What is the first-line treatment for managing tophi in patients with gout?

First-Line Treatment for Tophi in Gout

For patients with one or more subcutaneous tophi, initiate urate-lowering therapy (ULT) with allopurinol as the first-line agent, starting at a low dose (≤100 mg/day, or 50 mg/day if CKD stage ≥4) and titrating upward every 2-5 weeks to achieve a serum urate target of <6 mg/dL, with mandatory flare prophylaxis using colchicine 0.5-1 mg/day for at least 6 months. 1, 2

Why Tophi Mandate Treatment

• The presence of even a single subcutaneous tophus is a strong indication for initiating ULT, regardless of flare frequency or other factors 1, 3
• Tophi represent established monosodium urate crystal deposits that cause progressive joint destruction and disability if left untreated 4
• The 2020 ACR guidelines explicitly state this is a strong recommendation (not conditional), meaning the benefits clearly outweigh risks for virtually all patients 1

The Allopurinol Protocol for Tophi

Starting Dose

• Begin allopurinol at ≤100 mg/day in patients with normal renal function 1, 2
• Reduce to 50 mg/day for patients with CKD stage 4 or worse 1, 2, 5
• The FDA label emphasizes this is "not an innocuous drug" and requires individualized dosing, but strongly supports its use for tophi 6

Dose Titration Strategy

• Increase the dose by 100 mg every 2-5 weeks based on serum urate monitoring 1, 2, 3
• Continue titration until serum urate reaches <6 mg/dL (or <5 mg/dL for severe tophaceous disease) 1, 2
• Doses can be increased above 300 mg/day even in renal impairment with appropriate monitoring 2
• Check serum urate levels every 2-5 weeks during titration, then every 6 months once at target 2, 3

Target Serum Urate Levels

• Standard target: <6 mg/dL for all patients with tophi 1, 2, 3
• Intensive target: <5 mg/dL for patients with severe tophaceous gout, chronic arthropathy, or frequent attacks until complete crystal dissolution 1, 2, 3
• Lower serum urate levels correlate with faster velocity of tophi reduction in a linear relationship 7
• Avoid long-term maintenance of serum urate <3 mg/dL due to potential risks 1, 3

Mandatory Flare Prophylaxis

First-Line Prophylaxis Options

• Colchicine 0.5-1 mg/day for at least 6 months after starting ULT 1, 2, 8, 4
• Reduce colchicine dose in renal impairment and avoid with strong P-glycoprotein/CYP3A4 inhibitors 2
• Alternative: Low-dose NSAIDs (e.g., naproxen 250 mg twice daily) if colchicine is contraindicated 1, 2, 8
• Second alternative: Low-dose corticosteroids (prednisone or prednisolone) if both colchicine and NSAIDs are unsuitable 1, 8

Why Prophylaxis is Critical

• Dispersion of monosodium urate crystals during initial deposit dissolution increases acute flare risk 8
• Flares during ULT initiation contribute to poor treatment adherence 8
• Prophylaxis should continue for the first 6 months or until tophi resolve and no flares occur for several months 1, 2, 8

When Allopurinol Fails: Second-Line Options

Switching to Alternative XOI

• If allopurinol at maximum tolerated dose fails to achieve target serum urate or tophi persist, switch to febuxostat as the next XOI option 1
• Febuxostat can be titrated up to 120 mg daily in countries where approved 1
• For patients with febuxostat and history of cardiovascular disease, consider switching back to alternative ULT 1

Adding Uricosuric Agents

• Combination therapy (one XOI + one uricosuric like probenecid, fenofibrate, or losartan) is appropriate when serum urate target is not met with XOI monotherapy 1
• Probenecid is not recommended when creatinine clearance <50 mL/min 2

Pegloticase for Refractory Tophaceous Gout

• Reserve pegloticase 8 mg IV every 2 weeks only for severe gout with nonresolving tophi that is refractory to or intolerant of appropriately dosed oral ULT 1, 9
• In clinical trials, 45% of patients on pegloticase achieved complete resolution of one or more tophi versus 8% on placebo 1, 9
• Pegloticase is never first-line therapy for any gout scenario 1
• Monitor serum urate before each infusion; if urate rises >6 mg/dL on two consecutive measurements, consider discontinuation to reduce infusion reaction risk 9

Duration of Treatment

• Continue ULT indefinitely once initiated for tophi 1, 2, 3
• Approximately 40% of patients experience recurrence after stopping therapy 3
• The 2020 ACR guidelines strongly recommend continuing ULT indefinitely over stopping 1
• Tophi dissolution is a gradual process; complete resolution may take months to years depending on size and serum urate control 7, 4

Common Pitfalls to Avoid

• Starting allopurinol at too high a dose without gradual titration increases risk of flares and poor adherence 1, 2
• Failing to provide flare prophylaxis when initiating ULT leads to increased flares and treatment discontinuation 8, 4
• Not titrating to target serum urate but instead using fixed-dose allopurinol (e.g., stopping at 300 mg) leaves many patients undertreated 1
• Stopping ULT during acute flares—patients should continue ULT and add anti-inflammatory treatment 1
• Discontinuing ULT after tophi resolve leads to recurrence; treatment must be lifelong 2, 3
• Not monitoring serum urate levels regularly during titration prevents optimal dose adjustment 2, 3