High-dose interferon alfa-2b and ribavirin in patients previously treated with interferon: results of a prospective, randomized, controlled trial.

BACKGROUND

Kinetic studies have demonstrated a more rapid reduction in hepatitis C virus (HCV) RNA levels among patients taking high daily doses of interferon compared with those taking standard-dose interferon.

GOALS: To compare the efficacy and safety of high-dose interferon alfa-2b and ribavirin with standard-dose interferon alfa-2b and ribavirin in chronic hepatitis C patients previously treated with interferon.

STUDY: One hundred seven patients (30 interferon relapsers and 77 interferon nonresponders) were randomized to take either high-dose interferon alfa-2b in combination with ribavirin (group A) (consisting of 5 MU/d for 4 weeks, 5 MU three times weekly for 8 weeks, and then 3 MU three times weekly for 36 weeks) or standard-dose interferon alfa-2b and ribavirin (group B) for 48 weeks. Serum alanine transaminase (ALT), HCV RNA levels, and safety data were prospectively collected and compared during treatment and at week 24 of follow-up.

RESULTS

The mean serum ALT and HCV RNA levels, as well as the proportion of patients with genotype 1 and cirrhosis and who were African American, were similar in the two treatment groups at study entry. The rates of suppression of HCV RNA to undetectable levels at weeks 4, 12, and 48 were similar. In addition, the sustained virologic response rates at week 24 of follow-up were similar in groups A and B (29% vs. 39%, respectively, p = 0.277). Clinical variables that correlated with a sustained virologic response included a history of relapse to previous interferon therapy and non-1 HCV genotype ( p < 0.01).

CONCLUSIONS

Short-term, high-dose interferon alfa-2b and ribavirin failed to demonstrate a tangible benefit compared with standard-dose interferon alfa-2b and ribavirin. However, our study results and others suggest that standard-dose interferon and ribavirin for 48 weeks should be considered for selected patients who did not respond to previous interferon therapy.