Introduction
Krystexxa (pegloticase) is a recombinant uricase enzyme approved for the treatment of chronic gout refractory to conventional therapy. It represents a significant advancement in the management of severe gout cases where standard urate-lowering therapies have failed or are contraindicated.
Mechanism of Action
Krystexxa is a PEGylated recombinant uricase enzyme that catalyzes the oxidation of uric acid to allantoin, which is significantly more soluble and readily excreted by the kidneys. Unlike humans, who lack functional uricase, this enzyme provides an alternative pathway for uric acid metabolism, resulting in rapid and substantial reductions in serum uric acid levels.
Indications
Krystexxa is indicated for the treatment of chronic gout in adult patients who have failed to achieve normalized serum uric acid levels with xanthine oxidase inhibitors at maximum medically appropriate doses or for whom these drugs are contraindicated.
Dosage and Administration
- Standard dosing: 8 mg administered as an intravenous infusion every 2 weeks
- Administration: Must be diluted in 250 mL of 0.9% Sodium Chloride or 0.45% Sodium Chloride injection
- Infusion rate: Administer over no less than 120 minutes
- Premedication: Antihistamines and corticosteroids are recommended to minimize the risk of infusion reactions
- Special populations: No dosage adjustment required for renal or hepatic impairment
Pharmacokinetics
- Absorption: Administered intravenously, resulting in complete bioavailability
- Distribution: Volume of distribution approximately 7-8 L; limited tissue distribution due to PEGylation
- Metabolism: Metabolized via proteolysis; PEG component is excreted unchanged
- Elimination: Half-life approximately 10-14 days; eliminated primarily via renal excretion of metabolites
- Clearance: Approximately 10 mL/h
Contraindications
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- History of serious hypersensitivity reactions, including anaphylaxis, to pegloticase or any component of the formulation
Warnings and Precautions
- Infusion reactions: May be severe, including anaphylaxis; occur in approximately 26% of patients
- Gout flares: Frequently occur during initial therapy (up to 80% of patients); requires prophylaxis with NSAIDs or colchicine
- Congestive heart failure: Use with caution in patients with history of heart failure
- Immunogenicity: High incidence of anti-pegloticase antibodies, which may reduce efficacy and increase risk of infusion reactions
- Hemolysis and methemoglobinemia: Screen for G6PD deficiency prior to initiation
Drug Interactions
- No formal drug interaction studies conducted
- Theoretical interaction with other PEGylated drugs
- Concomitant use with uric acid-lowering agents may reduce efficacy of Krystexxa
- Immunosuppressants may affect antibody formation and efficacy
Adverse Effects
- Very common (>10%): Gout flares, infusion reactions, nausea, contusion or ecchymosis
- Common (1-10%): Constipation, chest pain, nasopharyngitis, vomiting
- Serious: Anaphylaxis (6.5%), infusion reactions (26%), congestive heart failure exacerbation
Monitoring Parameters
- Serum uric acid levels prior to each infusion (discontinue if levels >6 mg/dL)
- Vital signs during and after infusion
- Signs and symptoms of infusion reactions
- G6PD status prior to initiation (must be documented)
- Complete blood count, renal function, liver enzymes
- Monitoring for gout flares
Patient Education
- Importance of premedication before each infusion
- Recognition of infusion reaction symptoms (itching, rash, breathing difficulties)
- Need for gout flare prophylaxis as prescribed
- Understanding that treatment may initially cause increased gout flares
- Importance of not discontinuing therapy without medical guidance
- Reporting any signs of allergic reactions or unusual symptoms
- Continuing other prescribed medications unless advised by healthcare provider
References
1. Sundy JS, Baraf HS, Yood RA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials. JAMA. 2011;306(7):711-720. 2. FDA Prescribing Information: Krystexxa (pegloticase). Revised 2022. 3. Becker MA, Baraf HS, Yood RA, et al. Long-term safety of pegloticase in chronic gout refractory to conventional treatment. Ann Rheum Dis. 2013;72(9):1469-1474. 4. Strand V, Khanna D, Singh JA, et al. Improved health-related quality of life and physical function in patients with refractory chronic gout following treatment with pegloticase: evidence from phase III randomized controlled trials. J Rheumatol. 2012;39(7):1450-1457. 5. Saag KG, Fitz-Patrick D, So A, et al. Rapid and profound reduction of serum uric acid with pegloticase in patients with treatment-failure gout: results of phase 3 clinical trials. Arthritis Rheum. 2009;60(10):S410-S411.