Amantadine/Interferon-Alpha/Ribavarin Retreatment in Non-Responder Patients with Chronic Hepatitis C
- Some Improvements Observed with Amantadine/Interferon-Alpha/Ribavarin
Retreatment in Non-Responder Patients with Chronic Hepatitis C
A DGReview of :"Randomized, controlled trial with IFN-alpha combined
with ribavirin with and without amantadine sulphate in non-responders
with chronic hepatitis C"
Journal of Hepatology
By Deanna M Green, PhD
Greater sustained virologic response is observed with concomitant
amantadine, interferon (IFN)-alpha, ribavarin treatment in patients
with chronic hepatitis C who did not respond to initial antiviral
treatment, and particularly in those with low baseline viremia,
according to a recent German study.
IFN-alpha therapy is commonly used to treat patients with chronic
hepatitis C virus (HCV) infection and can be supplemented with
ribavarin for an enhanced effect. Unfortunately though, 30 to 50% of
treated patients do not respond to primary antiviral treatment.
Conflicting data exists regarding whether these non-responders should
be retreated with IFN-alpha and ribavarin and also whether another
antiviral such as amantadine sulphate should be added to retreatment.
Dr. Gerlinde Teuber at the Klinikum der Johann Wolfgang
Goethe-Universitat, Frankfurt, Germany, and colleagues conducted a
multi-centre, phase III, prospective study to evaluate the safety and
efficacy of IFN-alpha/ribavarin retreatment with or without
amantadine in patients with chronic hepatitis C who did not respond
to previous individual or combinatorial therapy with these drugs.
After stratification by HCV genotype, 225 patients were randomised to
receive IFN-alpha 2b (5 MU daily for 4 weeks, 5 MU thrice weekly for
20 weeks, followed by 3 MU thrice weekly for an additional 24 weeks)
combined with ribavirin (1000-1200 mg/day) either with or without
amantadine sulphate (200 mg/day) for 48 weeks. Efficacy and safety
were assessed up to 24 weeks after treatment.
Overall, 22% of all patients showed a sustained virologic response,
and therefore undetectable HCV-RNA levels, at follow-up. While there
was no statistically significant difference in the number of
responders in each treatment group, triple retreatment had higher
response rates, 25% compared to 18% in the non-amantadine group.
Further analysis revealed that patients with HCV non-1 genotype,
those with low pre-study viremia, and those who had undergone only 1
previous antiviral treatment were more likely to respond to
retreatment. Moreover, triple retreatment was more effective than
non-amantadine treatment in patients with low baseline viremia.
In addition, biochemical response as determined by normalisation of
alanine aminotransferase (ALT) levels showed similar trends between
groups as that observed for virologic response.
A similar range and frequency of adverse events were observed in each
treatment group. Most events were mild and reversible, though 8
severe (WHO grade IV) events occurred.
The authors conclude that "the addition of amantadine was well
tolerated and led to an improvement of sustained virologic responses
compared with retreatment with IFN-alpha/ribavarin alone, in
particular in patients with low baseline viremia."
Furthermore, they note that "the number of the previous antiviral
treatments is an important response predictor for retreatment," and
that "retreatment with IFN-alpha/ribavarin alone or in combination
with amantadine cannot be recommended in non-responders with multiple
previous antiviral treatment courses."
J Hepatol 2003 Oct;39:4:606-13. "Randomized, controlled trial with
IFN-alpha combined with ribavirin with and without amantadine
sulphate in non-responders with chronic hepatitis C"
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