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.