Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha†

Abstract

Successful treatment of chronic HCV with peginterferon (PEGIFN) and ribavirin (RVN) is often limited by anemia. We performed the present study to determine if utilizing epoetin alpha (EPO) with or without a higher dose of RVN could enhance sustained virologic response (SVR). We randomized 150 treatment-naive patients with chronic HCV genotype 1 into 3 treatment groups: (1) PEGIFN alpha-2b (1.5 g/kg/week) ؉ weight-based RVN (WBR) 13.3 mg/kg/day (800 to 1400 mg/day); (2) PEGIFN alpha-2b ؉ WBRVN ؉ EPO (40,000 U/week); or (3) PEGIFN alpha-2b ؉ higher dose WBR 15.2 mg/kg/day (1000 to 1600 mg/day) ؉ EPO. We initiated EPO at the onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When required, we reduced RVN by 200-mg steps. African Americans compose 36% of the population. A significantly smaller percentage of group 2 patients had a decline in hemoglobin to less than 10 g/dL (9% versus 34%; P < 0.05) and required that the RVN dose be reduced (10% versus 40%; P < 0.05) compared to group 1 patients. Despite this, SVR was similar in these groups (19% to 29%). SVR was significantly greater (P < 0.05) in group 3 patients (49%). This resulted from a significant decline (P < 0.05) in relapse rate; only 8% versus 38% for groups 1 and 2. Conclusion: We conclude that using EPO in all subjects at the initiation of PEGIFN and RVN treatment will not enhance SVR given the same starting dose of RVN. In contrast, a higher starting dose of RVN was associated with a lower relapse rate and higher rate of SVR. (HEPATOLOGY 2007;46:371-379.)

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.…”

“…Shiffman et al observed a lower rate of relapse and an higher rate of SVR in patients treated with a higher starting dose of RBV (15.2 mg/kg/day) plus Epoetin Alpha compared with those treated with a lower dose of RBV (13.3 mg/kg/day) with or without Epoetin Alpha [50].…”

Growth factors during HCV therapy may be “cost-effective”, but are they “effective”?

“…6,7 The most recent trial did not find that the use of growth factors improved sustained virologic response (SVR) with standard doses of peginterferon-␣ and ribavirin. 8 Only when growth factors were combined with higher ribavirin doses was an improvement in response rate observed.…”

“…Lower response rates are often observed when clinical trial data is translated into clinical practice, but these results ultimately mean that the Shiffman study may not support the use of growth factors given the SVR threshold of 50% declared by Del Rio. 8 In addition to concerns about the efficacy, these limited data sets have hindered the ability to establish safety in the HCV population. Red cell aplasia has been reported during erythropoietin therapy in at least one hepatitis C patient, and rapid rises in hemoglobin or targeting higher hemoglobin levels have been associated with an increased tendency to thrombotic episodes, a concern that is reflected in the package labeling for these agents.…”