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

Introduction. 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. Material and 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 (401(D) 180 pg/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. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.Roche Produtos Quimicos e FarmaceuticosUniv Sao Paulo, Sch Med, BR-05403000 Sao Paulo, BrazilInst Infectol Emilio Ribas, Sao Paulo, BrazilUniv Fed Rio Grande do Sul, Porto Alegre, RS, BrazilFed Univ Hlth Sci Porto Alegre, Porto Alegre, RS, BrazilState Univ Botucatu, Botucatu, SP, BrazilPontificia Univ Catolica Campinas, Campinas, SP, BrazilUniv Fed Bahia, Salvador, BA, BrazilIndiana Univ, Indiana, PA USAUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Fed Pernambuco, Recife, PE, BrazilSanta Casa de Misericordia de Goiania, Goiania, Go, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilHosp Alemao Oswaldo Cruz, Sao Paulo, BrazilRoche Prod Quim & Farmaceut, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc