Can pegloticase be restarted after discontinuation for reasons other than infusion reaction or hypersensitivity?

Pegloticase Restarting After Discontinuation

Pegloticase can be restarted after discontinuation for reasons other than infusion reactions or hypersensitivity, but patients face significantly increased risks of anaphylaxis and infusion reactions and require careful monitoring during retreatment. 1

FDA Guidance on Retreatment

The FDA label explicitly addresses this scenario and provides critical warnings:

• No controlled trial data exist on the safety and efficacy of retreatment with pegloticase after stopping treatment for longer than 4 weeks. 1
• Due to the immunogenicity of pegloticase, patients receiving retreatment may be at increased risk of anaphylaxis and infusion reactions. 1
• Patients receiving retreatment after a drug-free interval should be monitored carefully. 1

Clinical Evidence Supporting Retreatment

Despite FDA warnings, real-world evidence demonstrates that retreatment can be successful in select patients:

• A case series of four patients successfully retreated after gaps of 12-156 weeks showed that three of four patients achieved serum uric acid levels below 1.0 mg/dL and symptom resolution upon retreatment. 2
• One patient in this series experienced an infusion reaction and discontinued, while the other three tolerated retreatment without infusion reactions, gout flares, or adverse events. 2
• These patients were all prior responders to pegloticase, suggesting that successful initial response may predict better retreatment outcomes. 2

Critical Monitoring Requirements for Retreatment

When restarting pegloticase after any gap in therapy, the following precautions are mandatory:

• Administer in a healthcare setting with providers prepared to manage anaphylaxis and infusion reactions. 1
• Pre-medicate with antihistamines and corticosteroids before each infusion. 1
• Monitor serum uric acid levels prior to each infusion—if levels rise above 6 mg/dL, particularly with 2 consecutive levels above this threshold, the risk of infusion reactions dramatically increases and discontinuation should be considered. 1
• Infuse slowly over no less than 120 minutes (though recent data supports 60-minute infusions with concomitant methotrexate). 1, 3

Strategies to Improve Retreatment Success

Emerging evidence suggests immunomodulatory therapy may reduce the risk of antibody formation and improve outcomes:

• Concomitant methotrexate has been shown to recapture pegloticase response after development of anti-drug antibodies and may prevent antibody formation during retreatment. 4, 5
• Patients receiving concomitant immunomodulatory drugs had an adjusted hazard ratio of 0.52 (95% CI 0.37-0.75) for pegloticase discontinuation compared to those without immunomodulation. 5
• Consider initiating methotrexate or other immunomodulatory therapy at the time of pegloticase retreatment to reduce immunogenicity risk. 4, 5

Reasons for Discontinuation That May Allow Retreatment

The following scenarios represent discontinuation for reasons other than infusion reactions/hypersensitivity where retreatment may be considered:

• Symptom resolution leading to patient-initiated discontinuation (though premature, as tophi may not be fully resolved). 2
• Poor adherence or personal reasons unrelated to drug tolerability. 2
• Loss of therapeutic response (elevated serum uric acid) without infusion reactions—though this indicates antibody formation and retreatment carries higher risk. 6, 1
• Temporary interruption for other medical conditions or procedures. 2

Common Pitfalls to Avoid

• Do not restart pegloticase without ensuring the healthcare setting is equipped for anaphylaxis management—anaphylaxis can occur with any infusion, including after retreatment. 1
• Do not assume prior tolerance predicts future tolerance—the drug-free interval increases immunogenicity risk regardless of previous response. 1
• Do not restart without pre-medication with antihistamines and corticosteroids. 1
• Do not continue retreatment if serum uric acid levels rise above 6 mg/dL on consecutive measurements, as this signals antibody formation and dramatically increased infusion reaction risk. 6, 1

Gout Flare Prophylaxis During Retreatment

• Restart gout flare prophylaxis with NSAIDs or colchicine at least 1 week before reinitiating pegloticase and continue for at least 6 months unless contraindicated. 1
• Pegloticase should not be discontinued if a gout flare occurs during retreatment—manage the flare concurrently with appropriate anti-inflammatory therapy. 1