title: Network meta-analysis of direct-acting antivirals in combination with peginterferon-ribavirin for previously untreated patients with hepatitis C genotype 1 infection.
abstract: OBJECTIVE
  To conduct a network meta-analysis (NMA) to determine the comparative efficacy, as measured by sustained virological response (SVR), between boceprevir (BOC), telaprevir (TEL), faldaprevir (FAL), simeprevir (SIM) and sofosbuvir (SOF) in combination with peginterferon-ribavirin (PR) against a control of PR.
  
  
  METHODS
  A literature search was conducted to identify randomized controlled trials (RCTs) including adult patients with hepatitis C virus genotype 1 who were naive to any prior therapy. RCTs assessing standard duration therapy (SDT) or response-guided therapy (RGT) BOC, TEL, FAL, SIM or SOF in combination with PR against a control of PR were eligible for inclusion. All RCTs must have provided SVR at either 12 or 24 weeks post-therapy cessation.
  
  
  RESULTS
  We included nine RCTs. All direct-acting antivirals (DAAs) were found to perform better than PR. Additionally, SDT FAL was found to be better than the 240 mg RGT FAL regimen with the PR lead-in. A sensitivity analysis excluding RCTs with only SVR at 12 weeks was consistent with the results of the primary analysis. A sensitivity analysis removing an RCT assessing SIM that reported SVR of >60% in the PR control group additionally found that RGT SIM was superior to the 240 mg RGT FAL regimen with the PR lead-in.
  
  
  CONCLUSIONS
  Our analyses indicate that SDT and RGT regimens of DAAs plus PR do not differ greatly in terms of SVR among treatment-naive hepatitis C genotype 1 patients. More advanced Bayesian network meta-analyses are likely needed to incorporate a comprehensive evidence base, expanding beyond randomized clinical trials.
authors.affiliation: From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA edruyts@redwoodoutcomes.com.
authors.forename: E
authors.initials: E
authors.lastname: Druyts
authors.affiliation: From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Lorenzi
authors.affiliation: From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA.
authors.forename: K
authors.initials: K
authors.lastname: Toor
authors.affiliation: From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA.
authors.forename: K
authors.initials: K
authors.lastname: Thorlund
authors.affiliation: From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA From the Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada and Stanford Prevention Research Centre, Stanford University, Stanford, California, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Mills
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D001499:Bayes Theorem; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a