G-CSF Dosing in PEG-IFN-Alpha Induced Neutropenia
G-CSF Dosing in PEG-IFN-Alpha Induced Neutropenia
Summary: Many patients with chronic hepatitis C (HCV) infection undergoing treatment with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin develop neutropenia requiring dose reduction or granulocyte colony-stimulating factor (G-CSF) supplement. We analysed the database of patients who completed treatment for chronic HCV infection between 2003 and 2006. Patients with absolute neutrophil counts below 1000 cells/μL were initiated on G-CSF (G-CSF group) while a matching group of patients who received anti-HCV treatment without developing neutropenia were used as a control group (non-G-CSF group). Patients on the G-CSF arm were divided into two subgroups based on the timing of G-CSF administration relative to PEG-IFN-alpha administration. Of the 163 patients with HCV infection, 30 patients received G-CSF, most of who were maintained on 300 μg of G-CSF once a week. Administration of G-CSF 2 days before or after each dose of PEG-IFN-alpha did not make a significant difference in the neutrophil counts. In the G-CSF arm, 23 of 30 patients (77%) had undetectable end-of-treatment viral response which was comparable with 27 of 30 in the control group (90%; P = 0.17). There was no statistically significant difference in the sustained viral response between the two groups (61%vs 76%, P = 0.18). In most patients PEG-IFN-alpha induced neutropenia improved with a once-a-week dose of G-CSF with a comparable virological outcome. Timing of G-CSF administration did not make any significant impact on the patient's neutrophil counts but was better tolerated when given 2 days apart from PEG-IFN-alpha.
Haematological abnormalities including anaemia, thrombocytopenia and neutropenia are common adverse effects of antiviral agents that are used to treat chronic HCV infection. In the registration trial of pegylated interferon (PEG-IFN) and ribavirin, the incidence of dose reduction secondary to neutropenia was 18% for the arm receiving combination treatment with PEG-IFN (1.5 μg/kg/week) and ribavirin. The authors reported that <1% of patients discontinued treatment because of neutropenia. Similarly, in the study of PEG-IFN, the treatment group receiving PEG-IFN 180 μg every week with ribavirin needed dose modification because of neutropenia in 17% patients. However, only four patients (<0.5%) had to discontinue the treatment permanently because of neutrophil counts of <500 cells/μL. These studies suggest that PEG-IFN is commonly associated with a higher risk of neutropenia compared with standard IFN therapy, and this risk may be dose-related.
Haematopoietic growth factors such as erythropoietin and granulocyte colony-stimulating factor (G-CSF) are commonly used to overcome haematological side effects. An alternative approach to this has been reduction in the dose of the antiviral drugs causing these side effects. Haematological abnormalities, including anaemia and neutropenia, are the most common indications for dose reduction. This approach, however, has been found to be associated with higher rates of treatment failure.
Although G-CSF is commonly used to improve neutropenia, its optimal dose and timing of administration, and impact on clinical outcome have not been established. There is no published study that has looked into the dose or schedule of G-CSF administration. We conducted this study to find the optimal dose and timing of G-CSF administration relative to PEG-IFN for patients undergoing treatment of HCV infection. Our secondary goal was to assess the impact of G-CSF on HCV treatment outcome.
Summary: Many patients with chronic hepatitis C (HCV) infection undergoing treatment with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin develop neutropenia requiring dose reduction or granulocyte colony-stimulating factor (G-CSF) supplement. We analysed the database of patients who completed treatment for chronic HCV infection between 2003 and 2006. Patients with absolute neutrophil counts below 1000 cells/μL were initiated on G-CSF (G-CSF group) while a matching group of patients who received anti-HCV treatment without developing neutropenia were used as a control group (non-G-CSF group). Patients on the G-CSF arm were divided into two subgroups based on the timing of G-CSF administration relative to PEG-IFN-alpha administration. Of the 163 patients with HCV infection, 30 patients received G-CSF, most of who were maintained on 300 μg of G-CSF once a week. Administration of G-CSF 2 days before or after each dose of PEG-IFN-alpha did not make a significant difference in the neutrophil counts. In the G-CSF arm, 23 of 30 patients (77%) had undetectable end-of-treatment viral response which was comparable with 27 of 30 in the control group (90%; P = 0.17). There was no statistically significant difference in the sustained viral response between the two groups (61%vs 76%, P = 0.18). In most patients PEG-IFN-alpha induced neutropenia improved with a once-a-week dose of G-CSF with a comparable virological outcome. Timing of G-CSF administration did not make any significant impact on the patient's neutrophil counts but was better tolerated when given 2 days apart from PEG-IFN-alpha.
Haematological abnormalities including anaemia, thrombocytopenia and neutropenia are common adverse effects of antiviral agents that are used to treat chronic HCV infection. In the registration trial of pegylated interferon (PEG-IFN) and ribavirin, the incidence of dose reduction secondary to neutropenia was 18% for the arm receiving combination treatment with PEG-IFN (1.5 μg/kg/week) and ribavirin. The authors reported that <1% of patients discontinued treatment because of neutropenia. Similarly, in the study of PEG-IFN, the treatment group receiving PEG-IFN 180 μg every week with ribavirin needed dose modification because of neutropenia in 17% patients. However, only four patients (<0.5%) had to discontinue the treatment permanently because of neutrophil counts of <500 cells/μL. These studies suggest that PEG-IFN is commonly associated with a higher risk of neutropenia compared with standard IFN therapy, and this risk may be dose-related.
Haematopoietic growth factors such as erythropoietin and granulocyte colony-stimulating factor (G-CSF) are commonly used to overcome haematological side effects. An alternative approach to this has been reduction in the dose of the antiviral drugs causing these side effects. Haematological abnormalities, including anaemia and neutropenia, are the most common indications for dose reduction. This approach, however, has been found to be associated with higher rates of treatment failure.
Although G-CSF is commonly used to improve neutropenia, its optimal dose and timing of administration, and impact on clinical outcome have not been established. There is no published study that has looked into the dose or schedule of G-CSF administration. We conducted this study to find the optimal dose and timing of G-CSF administration relative to PEG-IFN for patients undergoing treatment of HCV infection. Our secondary goal was to assess the impact of G-CSF on HCV treatment outcome.
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