title: Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin ± amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial.
abstract: BACKGROUND
  A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care(pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin.
  
  
  METHODS
  Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (40KD) 180 µg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin).
  
  
  RESULTS
  The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin.
  
  
  CONCLUSIONS
  Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.
authors.affiliation: University of São Paulo School of Medicine and Instituto de Infectologia Emílio Ribas, São Paulo, Brazil. mgpessoa@usp.br
authors.forename: Mario G
authors.initials: MG
authors.lastname: Pessôa
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.forename: Paulo R L
authors.initials: PR
authors.lastname: Almeida
authors.forename: Giovanni F
authors.initials: GF
authors.lastname: Silva
authors.forename: Maria Patelli J S
authors.initials: MP
authors.lastname: Lima
authors.forename: Raymundo
authors.initials: R
authors.lastname: Paraná
authors.forename: Marco A
authors.initials: MA
authors.lastname: Lacerda
authors.forename: Edison R
authors.initials: ER
authors.lastname: Parise
authors.forename: José R B
authors.initials: JR
authors.lastname: Pernambuco
authors.forename: Suelene S
authors.initials: SS
authors.lastname: Pedrosa
authors.forename: Rosângela
authors.initials: R
authors.lastname: Teixeira
authors.forename: Hoel
authors.initials: H
authors.lastname: Sette
authors.forename: Fernando
authors.initials: F
authors.lastname: Tatsch
mesh_terms: D000328:Adult; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C100416:peginterferon alfa-2a