title: Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis.
abstract: BACKGROUND
  New direct-acting antiviral agents for hepatitis C genotype 1 infection, boceprevir and telaprevir, offer enhanced sustained virologic response (SVR) among both treatment-naïve and treatment-experienced patients.
  
  
  OBJECTIVE
  To determine the relative efficacy of the new direct-acting antiviral agents by applying a multiple treatment comparison meta-analysis.
  
  
  METHODS
  We included published Phase II and III randomized controlled trials evaluating head-to-head comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment comparison meta-analysis.
  
  
  RESULTS
  We included data from four boceprevir, three telaprevir and six peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin randomized controlled trials. Both boceprevir and telaprevir offer statistically superior outcomes for SVR, relapse and discontinuation due to adverse events than either peg-interferons among both treatment-naïve and treatment-experienced patients. Among treatment-naïve patients, clinical outcomes were similar for boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval (95% CrI) 0.41-1.91] and for relapse (OR 1.09, 95% CrI 0.19-4.84). Similarly, among treatment-experienced patients, clinical outcomes were similar for boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70-3.08) and for relapse (OR 0.35, 95% CrI 0.13-1.02). For treatment-naïve patients receiving standard-duration therapy, telaprevir yielded lower rates of anemia and neutropenia, but higher rates of rash and pruritus. For treatment-experience patients, all adverse event rates were higher with telaprevir.
  
  
  CONCLUSIONS
  Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1 treatment-naïve and treatment-experienced patients.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, The Ottawa Hospital, University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: R
authors.initials: R
authors.lastname: Lester
authors.forename: K
authors.initials: K
authors.lastname: Thorlund
authors.forename: E
authors.initials: E
authors.lastname: Druyts
authors.forename: A C
authors.initials: AC
authors.lastname: El Khoury
authors.forename: S
authors.initials: S
authors.lastname: Yaya
authors.forename: E J
authors.initials: EJ
authors.lastname: Mills
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D057186:Comparative Effectiveness Research; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a