Pegloticase
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Dosing and administration[2]
Pegylated uricase for refractory chronic gout. Premedicate (antihistamine and corticosteroid) and monitor serum urate before each infusion, stopping if it rises above 6 mg/dL (a marker of anti-drug antibodies and higher reaction risk). Co-administration with methotrexate improves durability of response.
| Indication | Starting dose | Titration and maximum |
|---|---|---|
| Refractory chronic gout | 8 mg IV infusion every 2 weeks. | Check serum urate before each infusion; discontinue if the pre-infusion urate exceeds 6 mg/dL (360 micromol/L) on two consecutive readings, given the higher anaphylaxis risk. |
Screen for G6PD deficiency before starting (contraindicated if deficient). Monitor serum urate before each infusion and stop for a rising urate, and consider methotrexate co-therapy to improve durability and reduce infusion reactions.
Monitoring
- Screen for G6PD deficiency before starting (contraindicated if deficient, hemolysis and methemoglobinemia risk).
- Monitor serum urate before each infusion; watch for anaphylaxis and infusion reactions.
- Discontinue other oral urate-lowering therapy during treatment.
Contraindications
- G6PD deficiency.
- Hypersensitivity to pegloticase.
Key interactions
- Do not co-administer oral urate-lowering therapy (can mask a rising urate that signals antibody formation).
- Methotrexate co-therapy is used deliberately to reduce immunogenicity.
Clinical notes
How it is used in gout
For patients in whom xanthine oxidase inhibitors, uricosurics, and other interventions have failed to reach target and who have frequent flares or nonresolving tophi, switching to pegloticase is strongly recommended; using pegloticase as first-line, or in mild disease with infrequent flares and no tophi, is strongly recommended against.[1]
Before starting
Background and monograph, not from the gout guideline: screen for G6PD deficiency before starting, as pegloticase is contraindicated in G6PD deficiency due to the risk of haemolysis and methaemoglobinaemia.
Monitoring
Background and monograph: monitor serum urate before infusions; a rising or elevated pre-infusion serum urate predicts loss of response and higher infusion-reaction risk and should prompt discontinuation. Follow the monograph for the exact protocol.
Common effects
Background clinical knowledge (not from the guideline): infusion reactions, gout flares, and nausea are common; flare prophylaxis is used as with other ULT.
Important cautions
Background and monograph, not from the gout guideline: risk of anaphylaxis and serious infusion reactions (boxed warning); contraindicated in G6PD deficiency; high cost and twice-monthly infusion burden factor into the recommendation against first-line use. Reconcile the full protocol with the product monograph.
References
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 https://doi.org/10.1002/acr.24180
- KRYSTEXXA (pegloticase) Product Monograph. Health Canada authorized product monograph. https://health-products.canada.ca/dpd-bdpp/