Treatment of Genotype 1 Chronic Hepatitis C: Increased Sustained Virological Response with High-dose RBV and Epoetin

By Marina Nunez, MD

Anemia is the most important side effect of ribavirin (RBV), leading often to dose reductions and premature treatment discontinuations. RBV dose reductions also are associated with decreased SVR.

The use of epoetin (EPO) [Procrit] has been proven to reduce anemia and the need for RBV dose reductions. Study results presented at the 56^th AASLD by Shiffman and colleagues show that the use of EPO also increases sustained virological response (SVR) when given with high doses of RBV to patients infected with HCV genotype 1.

Naïve patients infected with HCV-1 were randomly assigned to one of three treatment groups:

Group 1: pegylated interferon (pegIFN)-a-2b (1.5 mg/Kg/week) + RBV 13.3 mg/Kg/day (N=48)

Group 2: pegylated interferon (pegIFN)-a-2b (1.5 mg/Kg/week) + RBV 13.3 mg/Kg/day + EPO (N=49)

Group 3: pegylated interferon (pegIFN)-a-2b (1.5 mg/Kg/week) and RBV 15.2 mg/Kg/day +EPO (N=49)

In groups 2 and 3, EPO was given at onset of treatment if hemoglobin values were < 15 g/dL, or later on as soon as hemoglobin levels dropped below that threshold. EPO dose was initially 40,000 U/week, and doses were increased to 60,000 U/week if no response was obtained.

Groups were similar in age (median 48 years), proportion of African Americans (36-43%) and body weight (median 82.4 Kg). Only a minority of patients had cirrhosis, and although without statistically significant differences, it was more common in group 2 (8%) than in groups 1 (4%) and 3 (2%).

The table summarizes the results of the study:

* p<0.05 vs. groups 1 and 2

** % of responders at the end of treatment

*** p<0.05 vs. group 1

D/C: discontinuations

No significant differences were found in early virological response (EVR) or end-of-treatment response (ETR), but there were less relapses and higher proportion of SVR in the high RBV dose group compared to the others. SVR were higher in the high RBV dose group than in the other groups regardless of race ( African-American, 31% vs. 18%; non-African American, 53% vs. 30%).

In summary, the use of EPO significantly decreased the frequency of anemia, and the need for RBV dose reductions and premature discontinuations.

The use of higher doses of RBV (1,000-1,600 mg/day) decreased relapses and therefore increased SVR across all body weights and races in patients infected with HCV genotype 1.

These results are encouraging and suggest that the use of high doses of RBV should be evaluated in large clinical trials.

11/23/05

Reference
M L Shiffman and others. Treatment of chronic hepatitis C viris (HCV) genotype 1 with peginterferon alfa-2b (PEGIFN), high weight based dose ribavirin (RVN) and epoetin alfa (EPO) enhances sustained virologic response (SVR). Abstract 55. 56th annual meeting of the American Association for the Study of Liver Diseases (56th AASLD). November 11-15, 2005. San Francisco, CA.