title: 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.
authors.affiliation: Lazzaro Spallanzani National Institute for Infectious Diseases (INMI), Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Lanini
authors.forename: Alessia
authors.initials: A
authors.lastname: Mammone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Puro
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ippolito
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000453:epidemiology / Q000209:etiology*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D012254:Ribavirin; C486464:telaprevir