Will tophi resolve with treatment?

Will Tophi Resolve with Treatment?

Yes, tophi will resolve with appropriate urate-lowering therapy (ULT) that achieves sustained reduction in serum uric acid levels, with the treatment target being below 0.30 mmol/L (5 mg/dL) for optimal tophus resolution. 1

Treatment Targets and Monitoring

The primary goal for tophus resolution is achieving and maintaining serum urate levels below specific thresholds:

• Target serum urate below 0.30 mmol/L (5 mg/dL) for patients with tophi, which is more aggressive than the standard gout target of 0.36 mmol/L (6 mg/dL) 1, 2
• Monitor serum urate levels every 2-5 weeks during ULT titration, then every 6 months once target is achieved 2
• Assess tophi size and resolution as part of ongoing clinical evaluation 1, 2

The evidence strongly supports that achieving lower serum urate levels correlates with faster tophus reduction 3. There is a significant inverse correlation between serum urate levels and tophus resolution velocity 4.

First-Line Pharmacologic Approach

Allopurinol should be the first-line ULT for patients with tophi 2:

• Start at low dose (≤100 mg daily, lower in chronic kidney disease) 2
• Gradually titrate upward every 2-5 weeks until reaching serum urate target 2
• Doses above 300 mg daily are often necessary to achieve target urate levels 5
• Continue monitoring for adverse events, especially during initiation and dose escalation 2

Febuxostat is an alternative first-line agent if allopurinol is not tolerated or contraindicated 1, 2. Moderate-certainty evidence from a Cochrane review showed that longterm maintenance of serum uric acid <6.0 mg/dL with febuxostat led to reduction in tophi 3.

Flare Prophylaxis During ULT Initiation

Prophylaxis against gout flares must be initiated when starting ULT 2:

• First-line: Colchicine (up to 1.2 mg daily) 2
• Alternatives: Low-dose NSAIDs or glucocorticoids if colchicine is contraindicated or not tolerated 2
• Duration: Continue for at least 6 months after achieving target serum urate if tophi are present 1

Advanced Therapy for Refractory Disease

Pegloticase is strongly recommended for patients with nonresolving subcutaneous tophi despite optimal oral ULT 1:

• Moderate-certainty evidence shows biweekly pegloticase resolved tophi in 21/52 participants (40%) compared with 2/27 (7%) on placebo (RR 5.45,95% CI 1.38 to 21.54; NNTB 3) 6
• Complete resolution of at least one target tophus occurred in 45% of patients receiving pegloticase 8 mg every 2 weeks at 6 months 7
• Complete resolution of all photographed tophi was achieved by 34.8% of biochemical responders 4
• The mean velocity of tophus resolution was 60.1 mm²/month in responders with a mean projected time of complete resolution of 9.9 months (range 4.6-32.6 months) 4

Important caveat: More participants on biweekly pegloticase (15/85) withdrew due to adverse events compared to placebo (1/43), with infusion reactions being the most common reason (NNTH 7) 6. However, for patients with frequent gout flares (≥2 flares/year) or nonresolving subcutaneous tophi, the benefits clearly outweigh the risks 1.

Combination Therapy Considerations

Lesinurad plus allopurinol showed no clinically significant benefit for tophi resolution 6:

• Moderate-certainty evidence showed no difference in complete resolution of target tophus between lesinurad 200 mg plus allopurinol (11/53) versus placebo plus allopurinol (16/50) (RR 0.40,95% CI 0.04 to 4.57) 6
• Similar lack of benefit with lesinurad 400 mg plus allopurinol 6

Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat, though this is low-certainty evidence 6.

Surgical Intervention

Surgery is only indicated in selected cases 1, 2:

• Nerve compression 1, 2
• Mechanical impingement 1, 2
• Infection 1, 2
• Impending or severe debilitating complications including risk for permanent joint destruction 8

Medical therapy with ULT should always be the first-line approach 8. Published surgical series from 2002-2014 reported generally positive outcomes without major post-surgical complications, but surgery remains a rare consideration 8.

Critical Pitfalls to Avoid

• Never discontinue ULT once tophi have resolved - the ACR recommends continuing ULT indefinitely, as discontinuation frequently leads to recurrence of gout flares 2
• Do not rely solely on the standard 300 mg dose of allopurinol - this often fails to achieve target urate levels 5
• Do not stop KRYSTEXXA therapy if patients have a flare during treatment 7
• Ensure patients discontinue any oral urate-lowering agents before starting pegloticase and do not take oral ULT while on pegloticase 7

Timeline for Resolution

The velocity of tophus resolution varies considerably between patients, with the only patient characteristic correlating with resolution velocity being the baseline tophus area 4. With effective ULT maintaining serum urate below target levels, complete resolution can be expected within approximately 10 months on average for pegloticase responders, though individual timelines range from 4.6 to 32.6 months 4.