title: Combination therapy with amantadine and interferon in naïve patients with chronic hepatitis C: meta-analysis of individual patient data from six clinical trials.
abstract: 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.
authors.affiliation: Division of Gastroenterology, Ospedale Casa Sollievo Sofferenza, IRCCS, San Giovanni Rotondo 71013, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Leandro
authors.forename: Beat
authors.initials: B
authors.lastname: Helbling
authors.forename: Eberhard L
authors.initials: EL
authors.lastname: Renner
authors.forename: Marco
authors.initials: M
authors.lastname: Tabone
authors.forename: Laura
authors.initials: L
authors.lastname: Sidoli
authors.forename: Simona
authors.initials: S
authors.lastname: Caronia
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.forename: Stephan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.forename: Nicolina
authors.initials: N
authors.lastname: Cino
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D007372:Interferons; D000547:Amantadine; D000410:Alanine Transaminase