Meta-analysis: amantadine may lower the efficacy of pegylated interferon plus ribavirin in treatment-naive hepatitis C genotype 1 patients

Abstract

The current standard therapy for hepatitis C virus genotype 1 (HCV-1) infection is still suboptimal. Whether adding amantadine (AMA) to pegylated interferon (PEG-IFN) plus ribavirin (RBV) improves the virological response in treatment-naive HCV-1 patients remains unclear. Searches of the electronic databases including Embase, Medline, Cochrane Controlled Trials Register, and PubMed (updated to September 2011) and manual searches of the bibliographies were carried out. A meta-analysis of randomized clinical trials (RCT) comparing triple therapy (PEG-IFN+RBV+AMA) and double therapy (PEG-IFN+RBV) was performed. Five RCTs including 1425 patients were assessed. The meta-analysis based on the intention-to-treat analysis indicated that the sustained virological response (SVR) rate was significantly lower in the triple therapy group than in the double therapy group (44.2% vs. 49.2%, risk ratio (RR) 0.90, 95% confidence interval (CI) 0.80-1.00, p=0.05). The frequency of discontinuing therapy because of adverse events was similar in the two groups (RR 1.26, 95% CI 0.90-1.78, p=0.18). The sensitivity analysis including the four studies involving Caucasian populations revealed significantly lower SVR rates in the triple therapy group. The other sensitivity analyses also showed similar trends, but did not reach statistical significance. This meta-analysis suggests no beneficial effect of adding AMA to PEG-IFN+RBV in treatment-naive HCV-1 patients and even a trend towards a lower virological response rate in the triple therapy group. This study shows that the administration of AMA should be avoided in the management of treatment-naive HCV-1 patients.