New Medication Options for Gout Management
For patients with gout who have failed or cannot tolerate traditional therapies, pegloticase is strongly recommended as the most effective newer medication option, particularly for those with frequent gout flares (≥2 flares/year) or nonresolving subcutaneous tophi. 1, 2
Treatment Algorithm for Refractory Gout
First-Line Approach
- Allopurinol remains the first-line urate-lowering therapy (ULT), with dosage adjusted according to renal function 1
- If serum uric acid (SUA) target cannot be achieved with allopurinol, febuxostat should be considered as the next option 1
Second-Line Options
- If the first xanthine oxidase inhibitor (XOI) fails despite maximum-tolerated or FDA-indicated dose, switching to a second XOI is conditionally recommended over adding a uricosuric agent 1
- For patients with continued frequent gout flares or nonresolving tophi despite maximum XOI therapy, combination therapy options include:
Advanced Treatment for Refractory Gout
- Pegloticase is strongly recommended for patients who have failed XOI treatment, uricosurics, and other interventions, and who continue to have:
- Pegloticase (KRYSTEXXA) is administered as an 8mg intravenous infusion every two weeks 2
- Clinical trials have demonstrated that pegloticase provides:
- Profound lowering of serum urate levels
- Resolution of tophi
- Reduction in tender and swollen joint counts
- Decreased pain
- Improved quality of life 3
Important Considerations for Pegloticase
Indications
- Pegloticase is specifically indicated for chronic gout in adult patients refractory to conventional therapy 2
- Refractory gout is defined as failure to normalize serum uric acid and inadequate control of signs and symptoms with maximum XOI doses or when these drugs are contraindicated 2
Administration and Monitoring
- Must be administered in healthcare settings by providers prepared to manage anaphylaxis and infusion reactions 2
- Patients should receive premedication with antihistamines and corticosteroids 2
- Monitor serum uric acid levels prior to infusions and consider discontinuing if levels increase above 6 mg/dL, particularly when 2 consecutive levels above 6 mg/dL are observed 2
Limitations and Risks
- Major limitation is immunogenicity with potential for anti-drug antibodies leading to increased drug clearance, loss of efficacy, and infusion reactions 3
- Not recommended for treatment of asymptomatic hyperuricemia 2
- The optimal treatment duration has not been established, but experts suggest considering a switch to oral ULT once all tophi have disappeared 1
Emerging Therapies
- Lesinurad is a newer uricosuric agent that can be combined with XOIs for improved efficacy in patients with inadequate response to XOI monotherapy 1, 4
- IL-1 inhibitors (anakinra, canakinumab, rilonacept) are emerging as options for treating acute gout flares in patients with contraindications to traditional therapies 1, 4
- Other agents in development include arhalofenate, ulodesine, and levotofisopam 4
Treatment Target and Strategy
- Treatment of hyperuricemia should be target-oriented with a goal of maintaining SUA levels at <6 mg/dL (360 μmol/L) for most patients 1
- For patients with severe gout, a more aggressive target of <5 mg/dL (300 μmol/L) is recommended to hasten crystal dissolution 1
- A "start low, go slow" approach is recommended when initiating ULT to reduce the likelihood of acute flares during treatment initiation 1
Common Pitfalls to Avoid
- Failing to adjust allopurinol dosage according to renal function, which increases the risk of severe cutaneous adverse reactions (SCARs) 1
- Not monitoring SUA levels regularly to ensure treatment targets are being achieved 1
- Discontinuing ULT during acute flares, which can prolong the course of the disease 5
- Using pegloticase in patients with only infrequent flares (<2/year) and no tophi, where the benefits do not outweigh the risks and costs 1