A phase II dose finding study of darbepoetin alpha and filgrastim for the management of anaemia and neutropenia in chronic hepatitis C treatment

Abstract

Dose reductions of pegylated interferon alpha and ribavirin may be avoided by using growth factors. This phase II clinical trial assesses the dose, efficacy and safety of darbepoetin alpha and filgrastim for treatment of anaemia and neutropenia associated with combination therapy for hepatitis C virus (HCV). Chronic hepatitis C patients (n = 101) received pegylated interferon alpha-2b (1.5 mug/kg once weekly) and ribavirin (800-1400 mg once daily). Patients with anaemia [haemoglobin (Hb) </= 10.5 g/dL] received darbepoetin alpha (3 mug/kg once every 2 weeks); the dose was titrated to achieve a Hb level of 12.0 g/dL. Patients with neutropenia [absolute neutrophil count (ANC) </= 0.75 x 10(9)/L] received filgrastim with the dose titrated from 150 mug QW to 300 mug thrice weekly to maintain ANC >/= 0.75 x 10(9)/L and <10 x 10(9)/L. During antiviral therapy, 52% of patients required darbepoetin alpha, filgrastim or both. Hb at the time of darbepoetin alpha initiation was 10.2 +/- 0.4 g/dL. After 81 days of darbepoetin alpha, Hb increased by 1.9 +/- 1.0 g/dL to 12.1 +/- 1.1 g/dL (P < 0.0001). Filgrastim resulted in a significant increase in ANC [0.75 +/- 0.16 x 109/L to 8.28 +/- 5.67 x 10(9)/L (P < 0.0001)]. In treatment-naïve patients, 48% achieved sustained virological response (SVR), whereas 27% of patients previously treated with a course of pegylated interferon alpha achieved SVR. Low viral load, nongenotype 1 and treatment with growth factors were independently associated with SVR. Mild and severe anaemia were associated with quality of life impairments. Darbepoetin alpha resulted in an improvement in the Vitality domain of Short Form-36. No significant adverse events were related to growth factors. During anti-HCV therapy, filgrastim improved neutropenia and darbepoetin alpha improved both anaemia and quality of life. Future randomized clinical trials are needed to establish the impact of growth factors in improving sustained virological response.

Epoetin alpha improves the response to antiviral treatment in HCV-related chronic hepatitis

“…The results of previous studies [27,28,30,37,49,50,52,[56][57][58] and the present study have shown that the introduction of Epoetin Alpha therapy in patients treated with PEG-interferon alpha-2A and RBV for CH related to genotype 1b HCV infection leads to an improved adherence to treatment, and, consequently, to a significant improvement of SVR.…”

“…However, some studies have used decision analysis to estimate the cost-effectiveness of adjunctive therapy with erythropoietic growth factor (EGF) compared with that of standard care in the treatment of hepatitis C. The use of EGFs appears to be costeffective in patients with anaemia who are receiving combination therapy for HCV genotype 1, 2 or 3. Compared with The results of previous studies [27,28,30,37,49,50,52,[56][57][58] and the present study have shown that the introduction of Epoetin Alpha therapy in patients treated with PEG-interferon alpha-2A and RBV for CH related to genotype 1b HCV infection leads to an improved adherence to treatment, and, consequently, to a significant improvement of SVR.…”

Reduction in Neutrophil Count During Hepatitis C Treatment: Drug Toxicity or Predictor of Good Response?

“…In our study, two of four patients in whom peginterferon dose was reduced before 12th week of treatment suffered a relapse after stopping peginterferon and ribavirin. Unfortunately, the use of granulocyte-colony-stimulating factors has shown contradictory results [13,14]. New studies are needed to evaluate the safety and efficacy of lowering neutrophil thresholds for reducing the dose of peginterferon.…”

Peginterferon alfa and ribavirin for chronic hepatitis C in patients eligible for shortened treatment, re-treatment or in HCV/HIV co-infection: a systematic review and economic evaluation

“…[52][53][54][55][56][57][58][59] Two of the articles were abstracts 57,58 linked to full publications. 53,60 All of the included studies report peginterferon and ribavirin combination therapy in patients eligible for shortened treatment duration (i.e. those with specific genotypes as described in Chapter 3, Inclusion crtieria).…”