title: Sustained virological response with telaprevir in 1,078 patients with advanced hepatitis C: the international telaprevir access program.
abstract: OBJECTIVE
  There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24).
  
  
  METHODS
  1078 patients with bridging fibrosis (n=552) or cirrhosis (n=526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/mm(3), Hb >12/13 g/dl) and liver function (Albumin >3.3g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label.
  
  
  RESULTS
  Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR)=1.51, 95% CI 1.31-2.00, p=0.005), (B) subtype 1b (OR=1.63, 95% CI 1.18-2.24, p=0.0029), (C) alpha-fetoprotein <10 ng/ml (OR=2.50, 95% CI 1.87-3.36, p<0.0001) and (D) any prior response other than null (OR=3.29, 95% CI 2.40-4.52, p<0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail.
  
  
  CONCLUSIONS
  Naïve and experienced patients with advanced fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver function, can effectively and safely be treated by TVR triple therapy. Baseline predictors of outcome have been identified to optimize pre-treatment counselling.
authors.affiliation: Department of Medicine, Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy. Electronic address: massimo.colombo@unimi.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: Strasser
authors.affiliation: Liver Unit, Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Outpatient Clinic to HIV and Viral Hepatitis Division of Infectious Disease, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Abrao Ferreira
authors.affiliation: Department of Internal Medicine, First Medical Faculty, Charles University, and Central Military Hospital Prague, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Urbanek
authors.affiliation: Hospital Universitario 12 de Octubre, Sección de Aparato Digestivo, Madrid, Spain.
authors.forename: Inmaculada
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: Djamal
authors.initials: D
authors.lastname: Abdurakmonov
authors.affiliation: Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Bucharest, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Streinu-Cercel
authors.affiliation: Janssen Pharmaceutica, Beerse, Belgium.
authors.forename: Anke
authors.initials: A
authors.lastname: Verheyen
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: Wafae
authors.initials: W
authors.lastname: Iraqi
authors.affiliation: Tibotec Inc., Titusville, NJ, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: DeMasi
authors.affiliation: MetaVirology Ltd, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hill
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.affiliation: Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
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: Cirrhosis; Hepatitis C; Pegylated interferon; Telaprevir