title: Safety and on-treatment efficacy of telaprevir: the early access programme for patients with advanced hepatitis C.
abstract: OBJECTIVE
  Severe adverse events (AEs) compromise the outcome of direct antiviral agent-based treatment in patients with advanced liver fibrosis due to HCV infection. HEP3002 is an ongoing multinational programme to evaluate safety and efficacy of telaprevir (TVR) plus pegylated-interferon-α (PEG-IFNα) and ribavirin (RBV) in patients with advanced liver fibrosis caused by HCV genotype 1 (HCV-1).
  
  
  METHODS
  1782 patients with HCV-1 and bridging fibrosis or compensated cirrhosis were prospectively recruited from 16 countries worldwide, and treated with 12 weeks of TVR plus PEG-IFN/RBV, followed by 12 or 36 weeks of PEG-IFN and RBV (PR) alone dependent on virological response to treatment and previous response type.
  
  
  RESULTS
  1587 patients completed 12 weeks of triple therapy and 4 weeks of PR tail (53% cirrhosis, 22% HCV-1a). By week 12, HCV RNA was undetectable in 85% of naives, 88% of relapsers, 80% of partial responders and 72% of null responders. Overall, 931 patients (59%) developed grade 1-4 anaemia (grade 3/4 in 31%), 630 (40%) dose reduced RBV, 332 (21%) received erythropoietin and 157 (10%) were transfused. Age and female gender were the strongest predictors of anaemia. 64 patients (4%) developed a grade 3/4 rash. Discontinuation of TVR due to AEs was necessary in 193 patients (12%). Seven patients died (0.4%, six had cirrhosis).
  
  
  CONCLUSIONS
  In compensated patients with advanced fibrosis due to HCV-1, triple therapy with TVR led to satisfactory rates of safety, tolerability and on-treatment virological response with adequate managements of AEs.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Fondazione IRCCS Ca` Granda Ospedale Maggiore Policlinico, Universita` degli Studi di Milano, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Hospital Universitario 12 de Octubre, Sección de Aparato Digestivo, Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Fernández
authors.affiliation: I.M. Sechenov First Moscow State Medical University, E. M. Tareev Clinic for Nephrology, Internal and Occupational Medicine, Moscow, Russia.
authors.forename: D
authors.initials: D
authors.lastname: Abdurakhmanov
authors.affiliation: Viral Hepatitis Division of Infectious Disease, Outpatient Clinic to HIV, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: P A
authors.initials: PA
authors.lastname: Ferreira
authors.affiliation: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia.
authors.forename: S I
authors.initials: SI
authors.lastname: Strasser
authors.affiliation: Department of Internal Medicine, First Medical Faculty, Charles University, and Central Military Hospital Prague, Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Urbanek
authors.affiliation: Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases, "Prof. Dr. Matei Bals", Bucharest, Romania.
authors.forename: A
authors.initials: A
authors.lastname: Streinu-Cercel
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Verheyen
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: W
authors.initials: W
authors.lastname: Iraqi
authors.affiliation: Janssen Research and Development, Titusville, New Jersey, USA.
authors.forename: R
authors.initials: R
authors.lastname: DeMasi
authors.affiliation: Janssen Research and Development, High Wycombe, UK.
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.affiliation: Janssen-Cilag AG, Zug, Switzerland.
authors.forename: J M
authors.initials: JM
authors.lastname: Läuffer
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: I
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.affiliation: Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D016014:Linear Models; D008103:Liver Cirrhosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; 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
keywords: ANEMIA; HEPATITIS C; INTERFERON