A randomized controlled trial of amantadine plus interferon-alpha2a vs. interferon-alpha2a alone in naive patients with chronic hepatitis C randomized according to the early virological response to interferon-alpha2a monotherapy.
BACKGROUND
An early virological response to interferon-alpha treatment is a strong predictor of sustained response, but it has never been exploited to stratify patients in clinical trials.


OBJECTIVE
To evaluate the efficacy of amantadine plus interferon-alpha compared with interferon-alpha alone in naive patients with chronic hepatitis C who were randomized on the basis of the early virological response to interferon-alpha.


METHODS
One hundred and eighty-one patients received recombinant interferon-alpha2a (3 MU three times weekly) for 2 months and 164 were evaluated for early (i.e. month 2) virological response. Hepatitis C virus (HCV) RNA-negative patients (n = 66) were randomized to receive 3 MU of interferon-alpha three times weekly, with or without amantadine (200 mg/day); HCV RNA-positive patients (n = 98) were randomized to receive 6 MU of interferon-alpha three times weekly, with or without amantadine (200 mg/day). HCV RNA-positive patients at 6 months discontinued treatment, and all others completed 12 months.


RESULTS
At month 6, HCV RNA-negative patients made up 54.2% of the interferon + amantadine group and 42.0% of the monotherapy group (P = 0.07). At month 12, HCV RNA-negative patients made up 38.5% of the interferon + amantadine group and 28.4% of the monotherapy group (N.S.). The sustained virological response rates were 21.6% and 20.9%, respectively (N.S.).


CONCLUSIONS
The addition of amantadine does not enhance the sustained virological response to interferon-alpha in naive patients with chronic hepatitis C; however, an additive effect of amantadine occurs in the first 6 months, mainly in patients without an early response to monotherapy. Early response to interferon-alpha is a strong predictor of sustained virological response.
Angelico
M
M
Gastroenterology and Hepatology Clinics, University of Rome 'Tor Vergata' University of Rome 'La Sapienza' S. Giacomo Hospital, Rome, Italy. angelico@med.uniroma2.it
Cepparulo
M
M
Angelico
F
F
Francioso
S
S
Barlattani
A
A
Di Candilo
F
F
Della Vecchia
R
R
Demelia
L
L
De Sanctis
G
G
Gentile
S
S
Grieco
A
A
Parruti
G
G
Sabusco
G
G
Tarquini
L
L
Tosti
A
A
Zaru
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000547:Amantadine / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000998:Antiviral Agents; D004338:Drug Combinations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000547:Amantadine