Comparative Analysis of Adverse Events Linked to PEG-rhG-CSF and rhG-CSF in Real-World Settings: Disproportionate Examination of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) Database

Abstract

Purpose: Granulocyte-colony stimulating factor (G-CSF) is widely acknowledged for its efficacy in managing chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN), albeit accompanied by a spectrum of potential adverse effects. This study conducted a comprehensive analysis utilizing real-world data sourced from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, spanning the years 2004 to 2023, to assess and compare adverse events (AEs) associated with recombinant human G-CSF (rhG-CSF) and its polyethylene glycol-modified form (PEG-rhG-CSF).

Methods: A comprehensive analysis was conducted using FAERS data to evaluate the reporting proportion of AEs, gender-based disparities, and specific AEs such as bone pain. Statistical analyses included Reporting Odds Ratio (ROR) calculations and comparisons of median time to AE onset between PEG-rhG-CSF and rhG-CSF.

Findings: The study revealed that PEG-rhG-CSF was associated with a significantly higher number of adverse events (AEs) compared to rhG-CSF (76,155 vs. 10,953 cases). Female patients experienced a higher reporting proportion of AEs than males for both treatments, with PEG-rhG-CSF showing 54.2% of cases in females and rhG-CSF showing 46.1%, compared to 27.1% and 34.7% in males, respectively. Bone pain emerged as the most common AE, with PEG-rhG-CSF linked to 2,473 cases and rhG-CSF to 581 cases, and a higher reporting odds ratio (ROR = 1.17, 95% CI: 1.07-1.29) for PEG-rhG-CSF. Additionally, the median time to onset of AEs was shorter for PEG-rhG-CSF (3 days, IQR: 1-9) than for rhG-CSF (9 days, IQR: 2-42). Delayed AEs, such as splenomegaly, capillary leak syndrome, interstitial lung disease, and lung infiltration, were also identified, emphasizing the importance of close patient follow-up.

Implications: The study highlights significant differences in AE reporting proportion, gender disparities, and onset timing between PEG-rhG-CSF and rhG-CSF. These findings emphasize the need for close patient monitoring, especially for delayed AEs that may manifest after discharge. Further assessment of real-world data is warranted.

Keywords: FAERS database; PEG-rhG-CSF; adverse event; disproportionality analysis; granulocyte-colony stimulating factor; rhG-CSF.