Journal Article

A Systematic Review of Case Reports of Allergic and Hypersensitivity ADRs Associated with PEG-Granulocyte Colony-Stimulating Factor (PEG-GCSF) and PEG-Asparaginase (PEG-ASE)

You, Hyunmin, Cox, Anthony R, Jones, Marie-Christine, Chang, Hyuk

2024

Overview

Aim/Objective: The aims were two-fold: 1) to identify the type of allergic and hypersensitivity ADRs resulting from the administration of PEGylated granulocyte colony-stimulating factor (PEG-GCSF) and asparaginase (PEG-ASE) and 2) to assess the role of corticosteroids and anti-histamines in the management of these ADRs. Methods: A systematic literature review of case reports and case series on drug-induced ADRs was undertaken between January 1992 and November 23 for PEG-ASE, and from January 2000 to November 2023 for PEG-GCSF, reflecting the period since the drugs were first approved for clinical use. Data on the type, onset and management of hypersensitivity reaction was extracted. Results: 53 ADR cases were identified for PEG-ASE. Out of these, 9 cases related to a drug-induced allergic/hypersensitivity ADR mainly anaphylaxis or anaphylactoid-reactions. Most ADRS appeared after the 2nd or 3rd dose. However, 5 cases happened during or right after the first infusion. In all cases ADRs were managed by treatment with intravenous fluids, corticosteroids, and anti-histamines (diphenhydramine), with 3 cases requiring administration of epinephrine. For PEG-GSCF, 60 ADR cases were identified of which 5 were hypersensitivity/allergic reactions. Two cases presented as a skin rash appearing 1- or 7-days after PEG-GCSF administration and were managed with anti-histamines and corticosteroids. Three cases reported anaphylaxis or anaphylactoid reactions which appeared within 1 hour of the first dose and required fluid replacement, epinephrine, and corticosteroids. Interestingly, one case could be switched to non-PEG GCSF without ADRs. Conclusion: A similar number of ADR case reports were identified for both drugs over the period considered. Both PEGylated biologicals were associated with hypersensitivity/allergic reactions. Onset was varied, but early onset could suggest prior sensitisation to any component of the formulation, including PEG, a widely used pharmaceutical excipient also present in many personal care products. In the UK, premedication with anti-histamines and corticosteroids is recommended for PEG-ASE, but not PEG-GCSF. Further studies could determine if this recommendation should be expanded and whether patients should be assessed for possible hypersensitivity prior to initiating treatment with PEGylated biologicals.

• Publisher: Springer Nature B.V
• Subject: Allergic reactions / Allergies / Anaphylactoid reactions / Anaphylaxis / Antihistamines / Asparaginase / Biological products / Case reports / Colony-stimulating factor / Consumer products / Corticoids / Corticosteroids / Diphenhydramine / Drug dosages / Epinephrine / Granulocyte colony-stimulating factor / Granulocytes / Histamine / Hypersensitivity / Infusion fluids / Leukocytes (granulocytic) / Literature reviews / Steroids