Journal
CLINICAL PHARMACOLOGY IN DRUG DEVELOPMENT
Volume 12, Issue 8, Pages 826-831Publisher
WILEY
DOI: 10.1002/cpdd.1225
Keywords
Polyethylene glycol (PEG); anti-PEG antibody; PEGylated-granulocyte colony-stimulating factor (PEG-G-CSF); adverse event
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Polyethylene glycol (PEG) is a polymer attached to proteins to improve their half-life and efficacy, but PEG-G-CSF has been found to be immunogenic and potentially affect drug efficacy and safety. In this study, the relationship between anti-PEG antibody titers and the clinical impact of PEG-G-CSF was analyzed in 19 hematological patients. The results showed that high titers of anti-PEG antibodies may be associated with the development of adverse events after PEG-G-CSF administration, including noninfectious fever.
Polyethylene glycol (PEG) is a polymer covalently attached to proteins to improve their half-life and efficacy. We previously reported that the PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) is immunogenic, which could adversely impact drug efficacy and safety in animal models. Here, we analyzed the relationship between anti-PEG antibody titers and the clinical impact of PEG-G-CSF in 19 hematological patients. A gradual decrease of anti-PEG antibody titers from baseline was observed after PEG-G-CSF administration. Of the 19 participants, 10 were assessed for noninfectious fever after the first administration of PEG-G-CSF and three experienced this reaction. The receiver operating characteristic curve revealed that the cut-off values of pretreated anti-PEG IgM and IgG titers for noninfectious fever were set at 5.0 and 96.6 U/mL, respectively. All patients who experienced noninfectious fever had anti-PEG antibody titers above this cut-off value (P = .033). An enzyme-linked immunosorbent assay revealed that some anti-PEG antibodies in patients with anti-PEG antibody titers above the cut-off value reacted with the PEGylated liposome. These results indicate the reactivity of the anti-PEG antibodies to PEGylated therapeutics observed in hematologic patients and the possibility of the relationship between high titers of anti-PEG antibodies and the development of adverse events after PEG-G-CSF administration.
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