Combination therapy with amantadine and interferon in naïve patients with chronic hepatitis C: meta-analysis of individual patient data from six clinical trials.
OBJECTIVE
In chronic hepatitis C, clinical trials evaluating the efficacy of amantadine (AMA) and interferon (INF) compared to INF monotherapy, have produced conflicting results. We performed a meta-analysis of the individual patient's data from previous studies.


METHODS
Nine hundred and seventy-two patients from six European centres were evaluated by means of individual patient meta-analysis, using mixed models with centres and the centre-treatment interaction fitted as random variables.


RESULTS
At the end of therapy, virological responses were 38.5% (95% CI 34.1-42.8) after INF and AMA, and 29.5% (95% CI 25.5-33.6) after INF alone (P = 0.003). Sustained response occurred in 111 (23.1%; 95% CI 19.3-20.2) and 85 patients (17.3%; 95% CI 14.0-20.7), respectively (P = 0.03). Even accounting for the centre effect, therapy with AMA and INF was more effective than IFN alone (P = 0.029). When genotypes and viraemia levels were combined, the response rate after combination therapy doubled that observed with IFN alone in all subgroups, except those with low viraemia and genotypes 2 or 3.


CONCLUSIONS
In chronic hepatitis C, therapy with AMA and INF is effective and may be an alternative to INF and ribavirin in patients who cannot tolerate ribavirin.
Mangia
Alessandra
A
Division of Gastroenterology, Ospedale Casa Sollievo Sofferenza, IRCCS, San Giovanni Rotondo 71013, Italy.
Leandro
Gioacchino
G
Helbling
Beat
B
Renner
Eberhard L
EL
Tabone
Marco
M
Sidoli
Laura
L
Caronia
Simona
S
Foster
Graham R
GR
Zeuzem
Stephan
S
Berg
Thomas
T
Di Marco
Vito
V
Cino
Nicolina
N
Andriulli
Angelo
A
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000547:Amantadine / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D007372:Interferons; D000547:Amantadine; D000410:Alanine Transaminase