High-dose interferon alpha-2a with ribavirin and amantadine in naïve chronic hepatitis C patients--results of a randomized, prospective, pilot study.

BACKGROUND

Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules.

AIM

To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-alpha therapy vs. standard-dosage interferon-alpha therapy, in a triple therapy combination with ribavirin and amantadine.

METHODS

Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-alpha group (n = 15), receiving thrice weekly 6 MU interferon-alpha for 12 weeks, followed by 3 MU interferon-alpha for 36 weeks, or the high-dose interferon-alpha group (n = 15), receiving daily 9 MU interferon-alpha for 4 weeks, followed by 6 MU (weeks 5-8), 3 MU (weeks 9-12) and 1.5 MU (weeks 13-48) interferon-alpha. All patients were given ribavirin (1000-1200 mg) and amantadine (200 mg) daily for 48 weeks.

RESULTS

At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-alpha, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-alpha, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons.

CONCLUSIONS

The findings suggest that, although the difference between the response rates of standard and high-dose interferon-alpha regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-alpha therapy and an equal safety profile.