title: Boceprevir and telaprevir for chronic genotype 1 hepatitis C virus infection. A systematic review and meta-analysis.
abstract: BACKGROUND
  Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability.
  
  
  OBJECTIVE
  Assess benefits and harms of boceprevir (BOC) and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit.
  
  
  METHODS
  Search from 2009-2013 in PubMed, EMBASE, and "gray literature" of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed.
  
  
  RESULTS
  33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis, statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels. In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.
authors.affiliation: Obesity and Gastrointestinal Diseases Unit. Medica Sur Clinic & Foundation, Mexico City.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Manzano-Robleda
authors.affiliation: Obesity and Gastrointestinal Diseases Unit. Medica Sur Clinic & Foundation, Mexico City.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ornelas-Arroyo
authors.affiliation: National Institute of Public Health, Cuernavaca, Mexico.
authors.forename: Tonatiuh
authors.initials: T
authors.lastname: Barrientos-Gutiérrez
authors.affiliation: Liver Research Unit. Medica Sur Clinic & Foundation. Mexico City, Mexico.
authors.forename: Nahum
authors.initials: N
authors.lastname: Méndez-Sánchez
authors.affiliation: Liver Research Unit. Medica Sur Clinic & Foundation. Mexico City, Mexico.
authors.forename: Misael
authors.initials: M
authors.lastname: Uribe
authors.affiliation: Obesity and Gastrointestinal Diseases Unit. Medica Sur Clinic & Foundation, Mexico City.
authors.forename: Norberto C
authors.initials: NC
authors.lastname: Chávez-Tapia
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; 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 / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011392:Proline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; 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