Anemia associated with pegylated interferon-α2a and α2b therapy in hemodialysis patients

Aims: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) alpha(2a) versus alpha(2b) therapy in hemodialysis patients (HD) with chronic hepatitis C. Methods: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha(2a) or alpha(2b) therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha(2b) and 2 patients treated with PEG-IFN-alpha(2a). Secondary end-points were viral response and serious adverse events. Results: At 4 - 6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha(2a) when compared with alpha(2b) (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha(2a) and alpha(2b) in HD patients were different, the C-max, C-min and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha(2a) compared with PEG-INF-alpha(2b). Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha(2a) group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha(2b) group. Three (42%) subjects in the alpha(2a) group and 5 (55%) in the alpha(2b) group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha(2b) the viral response was sustained. Conclusions: In summary, patients treated with PEG-IFN-alpha(2a) have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha(2a) and alpha(2b). Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha(2).