Triple therapy for hepatitis C improves viral response but also increases the risk of severe infections and anaemia: a frequentist meta-analysis approach.

ABSTRACT

This meta-analysis assesses the efficacy and safety of triple therapy with either boceprevir or telaprevir compared to the standard of care (SoC), pegylated interferon plus ribavirin, in patients chronically infected with genotype 1 hepatitis C virus (HCV). We included 10 randomized controlled trials comprising 33 individual treatment arms which enrolled 5,312 subjects. Meta-analysis for sustained virologic response (SVR) provided evidence that triple therapy with either boceprevir or telaprevir increased response by 1.76 times (CI-95% 1.63-1.89) in comparison with SoC. However, heterogeneity was strong (I-2 79.7% p for heterogeneity <0.001). Meta-analyses for severe adverse reactions (SAE) indicated that triple therapy increased the risk of any SAE, severe anaemia and severe infections by 1.52 (CI-95% 1.23-1.88), 2.29 (CI-95% 1.49-3.52) and 1.87 (CI-95% 1.19-2.95) times, respectively, with no detectable heterogeneity. Additional analyses showed that the exposure to previous interferon treatment may explain all the heterogeneity found in the SVR meta-analysis. Meta-analysis for dose response found that both SVR and SAE have a direct log-linear association with telaprevir exposure. This study provides evidence that triple therapy with boceprevir and telaprevir can remarkably increase both the proportion of SVR and the occurrence of SAEs.