Granulocyte colony stimulating factor in HCV genotype‐1 patients who develop Peg‐IFN‐α2b related severe neutropenia: A preliminary report on treatment, safety and efficacy

Abstract

Dose reductions of Peg-IFNa because of severe neutropenia may affect the virologic response in patients with hepatitis C infection (HCV). Granulocyte colony-stimulating factor (G-CSF) has been used occasionally but studies addressing its safety and efficacy in the current treatment of HCV infection are missing. The database of 232 naïve patients with HCV genotype-1 who received PEG-IFNalpha2b 1.5 mcg/kg/week plus Ribavirin 800-1,400 mg/day and completed the treatment was examined. Nineteen patients who exhibited significant neutropenia and received 150-300 microg G-CSF (Group A) with 19 matched control patients who had dose reductions of Peg-IFNalpha according to the standard recommendations (Group B) were examined. None of the patients had treatment modifications due to thrombocytopenia or anemia. The mean decline of the neutrophils was similar in groups A and B (1,760 +/- 1,030/mm(3) at 11 +/- 8.6 weeks and 1,630 +/- 890 at 12.3 +/- 6.1, respectively). Nadir neutrophil values were also not statistically different. Patients who received G-CSF two before IFNalpha, maintained neutrophils between 1,400/mm(3) and 2,700/mm(3) and remained on G-CSF for 29 weeks (2-40). Virologic response at the end of treatment was observed in 12/19 (63%) patients and at 6 months follow-up in 6/19 (32%) in group A as compared to 9/19 (47%) and 4/19 (21%) in group B, respectively. No side effects related to G-CSF were encountered. Administration of G-CSF 2 days before Peg-IFNalpha is safe, maintains sustained neutrophil count, improves adherence to treatment and seems to increase the virologic response in patients infected with HCV genotype 1 who develop Peg-IFN-alpha2b related severe neutropenia.

Granulocyte colony‐stimulating factor for hepatitis C therapy‐associated neutropenia: systematic review and economic evaluation

“…Through sponsor contact, we received data from a clinical trial evaluating the efficacy of combination therapy with Peg‐IFN plus ribavirin [9]. Overall, 19 unique studies addressed effectiveness [9,27,28,31,32,35,36,38–41] and safety [24–26,29,30,33,34,37]. There was one RCT [32], three retrospective cohort studies [27–29] and 15 case series [9,24–26,30,31,33–41].…”

“…Hepatitis C virus (HCV) therapy varied across studies (Table 1). The definition of neutropenia ranged from neutrophil count <0.75 × 10 9 /L [9,24–26,30–32,34,36,37] to <1.0 × 10 9 /L [27–29,33,41]. In two studies, neutropenia was defined as a white blood cell count <3000/μL [38] or <2000/nL [40].…”

“…Four reported using filgrastim [23,32,33,37] and one used lenograstim [35]. Seven [25,27,28,31,38,40,41] did not specify the product used; however, based on the reported dosages, we assumed filgrastim was administered. The dose and schedule varied across studies (Table 2).…”

Colony-Stimulating Factors in the Prevention and Management of Infectious Diseases

“…45 Some preliminary reports suggest that more patients can experience a sustained virologic response when full-dose interferon therapy is continued with G-CSF support; however, rigorous randomized controlled studies are needed before routine use of G-CSF can be recommended in this setting. 46,47 Neutropenia caused by immunosuppressive medications, cytomegalovirus infection, antiviral therapy, or a combination thereof may also occur in patients who receive solid organ transplants. Neutropenia has been documented in 28% of renal transplant recipients in the first year posttransplant.…”

Pegylated Interferon and Ribavirin Dosing Strategies to Enhance Sustained Virologic Response

“…In a recent retrospective, cross-sectional study, Koskinas et al [53] found that HCV patients who were given G-CSF while undergoing combination therapy had higher rates of SVR (32% vs 21%), but this result was not statistically significant. Interestingly, the authors of this study found that members of the G-CSF group had higher rates of treatment adherence (95% vs 73.1%, P  < 0.05).…”