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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.

Publication ,  Journal Article
Ganson, NJ; Kelly, SJ; Scarlett, E; Sundy, JS; Hershfield, MS
Published in: Arthritis Res Ther
2006

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 +/- 2.1 mg/dl (mean +/- SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 +/- 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use.

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Published In

Arthritis Res Ther

DOI

EISSN

1478-6362

Publication Date

2006

Volume

8

Issue

1

Start / End Page

R12

Location

England

Related Subject Headings

  • Uric Acid
  • Urea
  • Urate Oxidase
  • Recombinant Proteins
  • Polyethylene Glycols
  • Middle Aged
  • Male
  • Immunoglobulin G
  • Hyperuricemia
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ganson, N. J., Kelly, S. J., Scarlett, E., Sundy, J. S., & Hershfield, M. S. (2006). 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. Arthritis Res Ther, 8(1), R12. https://doi.org/10.1186/ar1861
Ganson, Nancy J., Susan J. Kelly, Edna Scarlett, John S. Sundy, and Michael S. Hershfield. “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.Arthritis Res Ther 8, no. 1 (2006): R12. https://doi.org/10.1186/ar1861.

Published In

Arthritis Res Ther

DOI

EISSN

1478-6362

Publication Date

2006

Volume

8

Issue

1

Start / End Page

R12

Location

England

Related Subject Headings

  • Uric Acid
  • Urea
  • Urate Oxidase
  • Recombinant Proteins
  • Polyethylene Glycols
  • Middle Aged
  • Male
  • Immunoglobulin G
  • Hyperuricemia
  • Humans