Pegloticase Brand Name– Krystexxa
What is Pegloticase
Pegloticase is a parenteral, pegylated, recombinant mammalian urate oxidase enzyme.
Although the enzyme is present in most mammals, it is not found naturally in humans.
The novel mechanism of action of the drug lowers uric acid concentrations by converting uric acid into allantoin, which is a benign metabolite that is easily excreted in the urine.
The commercial product is produced by a genetically modified strain of E. coli and then covalently conjugated to monomethoxypoly(ethylene glycol) [mPEG].
In the pre-marketing clinical study of treatment-failure gout, 87.5% of patients treated with pegloticase 8 mg IV infusion every 2 weeks maintained a plasma uric acid concentration of 6 mg/dL or less for the 14-week study duration.
For chronic gout management, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) guidelines recommend ULT to achieve a target serum uric acid (sUA) level of less than 6 mg/dL to prevent the formation of crystals and to eliminate crystal deposition, thereby dissolving tophi.
A lower target (less than 5 mg/dL) is recommended for patients with severe disease.
Allopurinol is usually the first-line treatment agent due to effectiveness and cost considerations unless contraindications exist.
Allopurinol and febuxostat appear relatively similar as monotherapy in lowering serum urate concentrations and reducing gout flares with long-term (more than 1 year) of use.
Treatment guidelines recommend combination therapy with a uricosuric (e.g., lesinurad) plus a xanthine oxidase inhibitor (XOI) when treatment goals are not met with an XOI alone.
The use of pegloticase is usually reserved for severe, refractory chronic gout. In patients with crystal-proven, severe debilitating chronic tophaceous gout and poor quality of life, in whom the serum urate target cannot be reached with any other available drug at the maximal dosage (including combinations), pegloticase is indicated.
Once tophi disappear, then oral agents may again be considered. A boxed warning in the pegloticase label warns of the risk for infusion-related and hypersensitivity reactions.
Patients must be premedicated with antihistamines and corticosteroids before each dose and monitored for an appropriate time (1 hour) after each infusion.
The high cost of the drug relative to oral therapies, the need for intravenous parenteral administration and associated monitoring, and the incidence of anti-pegloticase antibody development (associated with therapy failure and increased hypersensitivity- and infusion-reactions) limit pegloticase use to refractory patients.
Indications
- gout
- gouty arthritis
- hyperuricemia
For the treatment of hyperuricemia due to chronic gout / gouty arthritis in patients refractory to conventional therapy (treatment-failure gout)
Side Effects
- anemia
- antibody formation
- arthralgia
- asthenia
- back pain
- chest pain (unspecified)
- constipation
- diarrhea
- dizziness
- dyspnea
- ecchymosis
- erythema
- fatigue
- fever
- gout
- headache
- heart failure
- hemolysis
- hypoglycemia
- hypotension
- infection
- infusion-related reactions
- malaise
- methemoglobinemia
- musculoskeletal pain
- nausea
- nephrolithiasis
- peripheral edema
- pharyngitis
- pruritus
- rash
- serious hypersensitivity reactions or anaphylaxis
- stroke
- urticaria
- vomiting
Monitoring Parameters
- serum uric acid
Contraindications
- Asian patients
- Black patients
- breast-feeding
- children
- G6PD deficiency
- heart failure
- hemolysis
- hyperuricemia
- infants
- infusion-related reactions
- methemoglobinemia
- neonates
- pregnancy
- requires a specialized care setting
- requires an experienced clinician
- serious hypersensitivity reactions or anaphylaxis
Interactions
- Allopurinol
- Colchicine; Probenecid
- Febuxostat
- Lesinurad; Allopurinol
- Probenecid
- Sulfinpyrazone
