Induced and pre-existing anti-polyethylene glycol antibody in a trial of every 3-week dosing of pegloticase for refractory gout, including in organ transplant recipients.

Introduction: Pegloticase, a PEGylated recombinant porcine uricase, is approved for treating refractory gout at a dose of 8 mg intravenous (IV) every 2 weeks. However, during phase 1 testing, pharmacokinetics supported less frequent dosing. Also, single doses of pegloticase unexpectedly induced antibodies (Ab) that bound to polyethylene glycol (PEG).

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo.

A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H(2)O(2) while depleting urate, offering an in vivo test of the antioxidant hypothesis.

Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout.

Objective: To evaluate the efficacy, immunogenicity, and tolerability of intravenous (IV) PEGylated recombinant mammalian urate oxidase (PEG-uricase) for the treatment of severe gout.

Methods: Single infusions of PEG-uricase (at doses ranging from 0.5 mg to 12 mg) were administered to 24 patients (6 cohorts of 4 patients each) in a phase I clinical trial.

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase.

PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 +/- 2.