Therapy with interferons have been associated with a greater decrease in absolute neutrophil counts than standard interferons, requiring dose reduction secondary to neutropenia in 18-20% of treated patients. While neutropeniais common, rarely is the neutropenia severe enough to warrant permanent discontinuationof therapy. If the neutrophil count drops below0.75 x 109 / L, the pegylated interferon doseshould be reduced by 50%. If the neutrophil count falls below 0.50 x 109 / L, therapy shouldbe discontinued. Neutrophil counts usuallyreturn to pretreatment levels within four weeksof stopping therapy. Based upon the concern ofneutropenia, many physicians have advocatedthe use of granulocyte-colony stimulating factor(G-CSF) at a dose of up to 300 ug subcutaneouslyper week. Currently, there are no clinical trials to demonstrate the effectiveness of G-CSF although clinical experience does support its efficacy in certain situations. Guidelines state: “Routine use of growth factors, such as epoetin and granulocyte colony-stimulating factor (G-CSF) was considered but not recommended”. At this time there is an absence of data supporting the preemptive use of growth factors in this patient population.
In most cases, the use is not routine but in order to enable therapy for hepatitis C.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. The VA wrote guidelines supporting its use under some conditions, but leukopenia has to be demonstrated first on interferon/ribavirin and dose reduction is to be pursued before Meupogen is used. In a recent database of patients who completed treatment for chronic HCV infection between 2003 and 2006, patients with absolute neutrophil counts below 1000 cells/microL 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 microg 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. Similar findings were reported by Lodato et a;.
A 2007 study from Georgia (Shavradze et al) concluded:” In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose (without reduction). Neupogen has the potential to improve adherence rates, which may in turn improve SVR.” The Authors reiterated this position in a 2009 editorial in a Georgian Medical News publication.In the USA, A 2005 TEC Assessment said this: “Well-designed RCTs show that patients treated with pegylated interferon, both as dual therapy and as monotherapy, experience higher sustained viral response rates than those treated with non-pegylated interferon. Patients with genotypes 2 and 3 experience the highest response, with rates in excess of 80%. Patients with the harder to treat genotype 1 nevertheless benefit, with up to 46% of patients experiencing an SVR in one of the trials. Pegylated interferon also appears to be relatively cost-effective in both monotherapy and dual therapy, with cost per QALY estimates remaining generally under 30,000 pounds sterling. The most favourable estimates were for patients with genotypes 2 and 3. Pegylated interferon is a relatively new intervention in the treatment of hepatitis C and therefore there are areas where further research is needed. These include: efficacies of therapy with PEG-alpha-2a vs PEG-alpha-2b; retreatment of previous non-responders using pegylated interferon; efficacy of treatments and long-term outcomes in patients who have other co-morbidities; prospective tests of rules governing stopping treatment; treating patients with acute hepatitis C; problems that may occur in a minority of patients with hepatitis C, such as cryoglobulinaemia and vasculitis; additional psychological effects on quality of life due to hepatitis C and also on the treatment of children and adolescents with hepatitis C.” On the balance, I read it as recommending Neupogen.
Last Modified: February 08, 2012
2.Lodato F, Azzaroli F, Tame MR, Di Girolamo M, Buonfiglioli F, Mazzella N, Cecinato P, Roda E, Mazzella G.G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence.
World J Gastroenterol 2009 November;15(43):5449-5454
3.NY State Gudielines for Hep. C. - http://www.health.state.ny.us/diseases/communicable/hepatitis/guidelines/appena.htm
5.Koirala J, Gandotra SD, Rao S, Sangwan G, Mushtaq A, Htwe TH, Adamski A, Blessman D, Khardori NM. Granulocyte colony-stimulating factor dosing in pegylated interferon alpha-induced neutropenia and its impact on outcome of anti-HCV therapy.J Viral Hepat. 2007 Nov;14(11):782-7.