Recombinant Uricase — Urate-Lowering Biologic Pregnancy: Avoid — no human data; porcine-baboon uricase with PEG; insufficient safety data.

Pegloticase (Recombinant PEGylated Uricase — Refractory Gout)

Brand names: Krystexxa

Adult dose

Dose: 8 mg IV infusion every 2 weeks

Route: IV infusion over ≥2 hours (in diluted 250 mL normal saline)

Frequency: Every 2 weeks (ongoing until treatment failure or sustained urate normalisation)

Max: 8 mg per infusion

Recombinant porcine-baboon chimeric uricase conjugated to PEG. Converts urate to allantoin (5–10× more soluble — excreted in urine). Achieves urate <6 mg/dL in 42% of patients with refractory gout. FDA approved 2010; MHRA via Special Access/named patient route in UK. Must pre-medicate with antihistamine, corticosteroid, and paracetamol before each infusion.

Paediatric dose

Route:

Not licensed in paediatrics.

Dose adjustments

Renal

No dose adjustment required — uricase mechanism unaffected by renal impairment; indeed, particularly useful in CKD where standard ULTs are limited.

Hepatic

No dose adjustment required.

Clinical pearls

CRYSTAL and OPENlabel trials (Sundy et al. NEJM 2011): pegloticase 8 mg biweekly — 42% achieved serum urate <6 mg/dL at 3–6 months vs 0% placebo; significant tophus reduction. Most dramatic urate reduction of any available ULT (drops urate to near zero in responders)
Serum urate monitoring before EVERY infusion: if urate >6 mg/dL on two consecutive pre-infusion measurements = treatment failure/immunogenicity — STOP pegloticase immediately (infusion reaction risk is very high); do not administer another infusion
Methotrexate co-administration (MIRROR trial 2023): pegloticase + methotrexate — significantly increased sustained response rate (71% vs 38% MTX-naive) by reducing anti-PEG antibody formation. Co-administration with low-dose immunosuppression now standard in many centres to reduce immunogenicity

Contraindications

G6PD deficiency (hydrogen peroxide generated by uricase reaction — oxidative haemolysis in G6PD deficiency; screen before use)
Concomitant urate-lowering therapy (must stop allopurinol/febuxostat ≥4 weeks before — they lower urate and prevent monitoring of immunogenic treatment failure)

Side effects

Infusion reactions (26% vs 5% placebo — monitor serum urate before each infusion; rising urate = antibody formation = high infusion reaction risk; STOP if urate >6 mg/dL on 2 consecutive measurements)
Anaphylaxis (6.5% — most within first 2 hours; always administer in monitored setting with resuscitation available)
Gout flares (paradoxical — mobilisation of urate deposits; pre-treat with colchicine or NSAIDs for 1–6 months)
Cardiovascular events (higher incidence in trials — patients pre-selected for high CV risk comorbidities)

Interactions

Other urate-lowering therapy (do NOT combine — allopurinol/febuxostat mask immunogenic treatment failure by lowering urate independently; makes monitoring unreliable)
PEG-containing products (potential cross-reactivity with PEGylated biologics)

Monitoring

Serum urate before EVERY infusion (stop if >6 mg/dL on 2 consecutive measurements)
G6PD screen before first infusion
Infusion-related reaction signs (during each 2-hour infusion + 1h post — full resuscitation available)
Renal function (urate crystalluria with large urate load dissolution)

Reference: BNFc; BNF 90; Sundy et al. NEJM 2011 (CRYSTAL trial); Botson et al. ACR 2023 (MIRROR trial); FDA Krystexxa PI; BSR Gout Guidelines 2022. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways