Peginterferon Regimens for Treating HCV Infection: Alfa-2a vs. Alfa-2b

Rajesh T. Gandhi, MD

Disclosures

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Efficacy and tolerability were similar between regimens.

Hepatitis C virus (HCV) infection is treated with peginterferon in combination with ribavirin. Two main types of peginterferon-based regimens are currently available: alfa-2a and alfa-2b; which regimen is better is unknown. To address this issue, the IDEAL study team (supported by grants from industry) conducted a multisite, randomized trial comparing two different doses of weight-based alfa-2b (standard, 1.5 μg/kg/week; or low, 1.0 μg/kg/week) and fixed-dose alfa-2a, each in combination with ribavirin, in 3070 adults with HCV genotype 1 monoinfection.

Sustained virologic response (SVR) rates were similar among groups: 40% for standard-dose alfa-2b, 38% for low-dose alfa-2b, and 41% for alfa-2a. (Although the end-of-treatment response rate was higher with alfa-2a, more patients in this group relapsed, resulting in a similar SVR rate.) However, women seemed to have a higher SVR rate with standard-dose than with low-dose alfa-2b. HCV RNA levels at weeks 4 and 12 were strongly predictive of ultimate outcome. For example, among patients whose baseline HCV RNA had dropped <1 log10 IU/mm3 at week 4, <5% had an SVR, whereas among those with undetectable HCV RNA at week 4, 86% had an SVR. The types and rates of adverse events were similar among the groups, although the frequency of anemia and neutropenia was lower in the low-dose alfa-2b group.

Comment

The mean dose of ribavirin was lower in the alfa-2b groups than in the alfa-2a group because, when the study was initiated, weight-based dosing of ribavirin was not FDA approved for use with alfa-2b. Thus, the trial was not a direct comparison of the two types of peginterferon. Nevertheless, the three peginterferon regimens used in the study were similarly efficacious and had comparable adverse-event profiles. Where do we go from here in improving treatment for HCV infection? The next step is likely to be the use of HCV protease inhibitors in combination with peginterferon and ribavirin (JW Gastroenterol Apr 29 2009).

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