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Amantadine in chronic hepatitis C therapy (Part 1) 08/02/2002
Amantadine, a drug known to be effective against the influenza virus, has
also been studied over the last few years as a possible treatment for
chronic hepatitis C infection. This viewpoint will examine the data on the
use of amantadine to treat hepatitis C patients who have not had prior
therapy for
HCV ("naïve" patients). Next month's Viewpoint will examine its role in the
yreatment of patients who have relapsed from or failed prior therapies.
The role of amantadine in the therapy of naïve patients has been the subject
of several studies. Because of the controversy around amantadinme, it may be
worth discussing these studies in some detail. First, in one study, Zeuzem
and colleagues assigned 119 patients randomly to a regimen of either
interferon plus amantadine or interferon alone. After one year, one-third of
patients receivign either treatment had undetectable amount of HCV in their
blood. Six months later the so-called "sustained virologic response rate,"
or SVR, were 10% in the group receiving amantadine and 22% in the group who
received only interferon.
Three additional studies also found that amantadine added little benefit to
treatment with interferon. Caronia et al. reported SVRs of 23% and 17%,
while Tabone et al reported SVR's of 24% and 17%, for combination treatment
an interferon alone, respectively. A third study, published in February of
this
year, showed similar sustained virologic response rates of 21% and 14%,
respectively. While the amantadine patients had SVRs that were slightly
higher, the conclusion was that addition of amantadine did not lead to
statistically significant differences in response rates.
In one final report of more than 200 patients, those taknig amatadine did
appear to have a slightly better result, with nearly 30% responding to
amantadine plus interferon, against only 17% for interferon alone. There is
no clear explanation for the discrepancy between this last study and the
ones
noted above.
Why should we care? The most effective therapies currently available for
hepatitis C infection (alpha interferon/pegylated interferon in combination
with ribavirin) produce sustained virologic response rates that are far
superior to those reported above--as high as 60%. We can undoubtedly expect
to see reports on the combination of pegylated interferon with amantadine.
But I am not optimistic that these studies will add more to the management
of naive, HCV-infected patients. If there is any role for amantadine it may
lie in its use combined with future, non-interferon based drugs, or in the
patient who has relapsed or failed to respond to interferon and ribavirin
combinations-- a topic we will discuss in more detail in my next Viewpoint.
References:
Zeuzem S, Teuber G, Naumann U, Berg T, Raedle J, Hartmann S, Hopf U
Randomized, double-blind, placebo-controlled trial of interferon alfa2a with
and without amantadine as initial treatment for chronic hepatitis C.
Hepatology. 2000; 32:835-41
Mangia A, Minerva N, Annese M, Leandro G, Villani MR, Santoro R, Carretta V,
Bacca D, Giangaspero A, Bisceglia M, Ventrella F, Dell'Erba G, Andriulli A.
A randomized trial of amantadine and interferon versus interferon alone as
initial treatment for chronic hepatitis C. Hepatology. 2001;33:989-93
Caronia S, Bassendine MF, Barry R, Mills P, Naoumov NV, Fox R, Lowes J,
Hollanders D, Murray-Lyon L, Irving WL, Goldin RD, Foster GR; UK Amantadine
Study Group. Interferon plus amantadine versus interferon alone in the
treatment of naive patients with chronic hepatitis C: a UK multicentre
study.
J Hepatol. 2001;35:512-6.
Tabone M, Laudi C, Delmastro B, Biglino A, Andreoni M, Chieppa F, Bonardi R,
Cariti G, Cusumano S, Brunello F, Calleri G, Manca A, Della Monica P, Sidoli
L, Rizzetto M, Pera A. Interferon and amantadine in combination as initial
treatment for chronic hepatitis C patients. J Hepatol. 2001;35:517-21
Helbling B, Stamenic I, Viani F, Gonvers JJ, Dufour JF, Reichen J, Cathomas
G, Steuerwald M, Borovicka J, Sagmeister M, Renner ELInterferon and
amantadine in naive chronic hepatitis C: a double-blind, randomized,
placebo-controlled trial. Hepatology. 2002; 35:447-54.
Written by Chinweike Ukomadu, M.D., Ph.D.
Content created 8/2/02
Content last reviewed August 2, 2002