title: A randomized controlled trial of pegylated interferon alpha-2a (40 KD) or interferon alpha-2a plus ribavirin and amantadine vs interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C.
abstract: We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN) alpha-2a or conventional IFN alpha-2a would improve sustained virological response (SVR) rates over dual therapy with IFN alpha-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naïve patients were randomized to 48 weeks of treatment with: PEG-IFN alpha-2a 180 microg/week (group A) or IFN alpha-2a 3 MU tiw (groups B and C). All patients received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200 mg/day. SVR was defined as an undetectable HCV RNA after 24 weeks of untreated follow-up. At the end of therapy, 74.4% (95% CI 0.66-0.82) of patients in group A were HCV RNA-negative compared with 42.5% (95% CI 0.33-0.50) of those in group B (P = 0.0001) and 48.8% (95% CI 0.40-0.56) of those in group C. SVR was achieved in a significantly greater proportion of patients in group A compared with groups B and C: 65.3% (95% CI 0.53-0.56), 33.3% (95% CI 0.25-0.41) and 44.6% (95% CI 0.36-0.53; P = 0.0001) respectively. In patients with genotype 1, SVR rates were 55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender and age. In treatment-naive patients with chronic hepatitis C, triple therapy with PEG-IFN alpha-2a, RBV and AMA produces higher SVR than dual or triple therapy with conventional IFN alpha-2a.
authors.affiliation: Division of Gastroenterology, Casa Sollievo della Sofferenza Hospital, IRCCS, 71013 San Giovanni Rotondo, Italy. a.mangia@tin.it
authors.forename: A
authors.initials: A
authors.lastname: Mangia
authors.forename: G L
authors.initials: GL
authors.lastname: Ricci
authors.forename: M
authors.initials: M
authors.lastname: Persico
authors.forename: N
authors.initials: N
authors.lastname: Minerva
authors.forename: V
authors.initials: V
authors.lastname: Carretta
authors.forename: D
authors.initials: D
authors.lastname: Bacca
authors.forename: M
authors.initials: M
authors.lastname: Cela
authors.forename: M
authors.initials: M
authors.lastname: Piattelli
authors.forename: M
authors.initials: M
authors.lastname: Annese
authors.forename: G
authors.initials: G
authors.lastname: Maio
authors.forename: D
authors.initials: D
authors.lastname: Conte
authors.forename: V
authors.initials: V
authors.lastname: Guadagnino
authors.forename: V
authors.initials: V
authors.lastname: Pazienza
authors.forename: D
authors.initials: D
authors.lastname: Festi
authors.forename: F
authors.initials: F
authors.lastname: Spirito
authors.forename: A
authors.initials: A
authors.lastname: Andriulli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000547:Amantadine / Q000008:administration & dosage* / Q000009:adverse effects; D001707:Biopsy, Needle; D016009:Chi-Square Distribution; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007150:Immunohistochemistry; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011336:Probability; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012720:Severity of Illness Index; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C100416:peginterferon alfa-2a