title: Treatment of chronic HCV genotype 1 infection with telaprevir: a Bayesian mixed treatment comparison of fixed-length and response-guided treatment regimens in treatment-naïve and -experienced patients.
abstract: BACKGROUND
  Telaprevir (TVR) has been approved for response-guided-therapy (RGT) of chronic hepatitis C (HCV) genotype-1-infection in treatment-naïve and -experienced patients. In RGT-regimens patients that did not achieve extended rapid-virological-response (eRVR) within the first 4-12 weeks undergo treatment for 48-weeks, whereas in fixed-length-treatment (FLT) patients are treated for a fixed-duration regardless of their RVR.
  
  
  METHODS
  This systematic review and Bayesian mixed-treatment-comparison (MTC) aimed to compare the efficacy and safety of standard-therapy with pegylated-interferon-α/ribavirin (Peg-IFN-α/RBV (48 weeks), group A), FLT with TVR, Peg-IFN-α/RBV for 12 weeks with a long (+36 weeks, group B) or short (+12 weeks, group C) tail of Peg-IFN-α/RBV treatment, and RGT with 12 weeks of TVR, Peg-IFN-α/RBV followed by 12 weeks of Peg-IFN-α/RBV (group D) or no therapy (group E).
  
  
  RESULTS
  We identified seven randomized controlled trials including 3505 patients. Compared to standard-treatment (group A), treatment-naïve patients allocated to groups B, C, and D were significantly more likely to achieve sustained-virological-response (SVR, odds ratios (OR): B vs. A 3.5 (credibility interval [CrI] 2.2-5.4), C vs. A 3.0 (CrI 1.8-4.9), D vs. A 3.4 (CrI 2.5-4.6)). Treatment-experienced patients achieved increased SVR rates when they were treated in group B (OR: 8.2 (CrI 5.0-13.5)), C (OR 7.0 (CrI 3.9-12.8)), or simulated group D (OR 8.2 (CrI 4.3-15.3)). Patients treated with short RGT (simulated group E) did also have a significant improvement when they were treatment-experienced (simulated OR 3.6 (CrI 1.6-8.2)), whereas the effect was not significant in treatment-naïve patients (OR E vs. A 1.6 (CrI 0.9-2.7)).
  
  
  CONCLUSIONS
  Long FLT and RGT regimens are useful treatment options for HCV-genotype-1 in both treatment-naïve and -experienced patients. A short 24-weeks FLT regimen does not seem to be inferior and should further be evaluated in clinical trials to reduce side effects and costs of treatment.
authors.affiliation: Division of Gastroenterology and Endocrinology, University Medical Center Goettingen, Georg-August-University Goettingen, Goettingen, Germany. ahmad.amanzada@med.uni-goettingen.de.
authors.forename: Armin D
authors.initials: AD
authors.lastname: Goralczyk
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.forename: Ahmad
authors.initials: A
authors.lastname: Amanzada
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001499:Bayes Theorem; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D009842:Oligopeptides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000627:therapeutic use; 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; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a