title: Efficacy of telaprevir-based therapy in stable liver transplant patients with chronic genotype 1 hepatitis C.
abstract: Background and rationale. The REPLACE study (NCT01571583) investigated telaprevir-based triple therapy in patients who have recurrent genotype 1 hepatitis C virus (HCV) infection following liver transplantation and are on a stable immunosuppressant regimen of tacrolimus or cyclosporin A. Patients received telaprevir 750 mg 8-hourly with pegylated interferon 180 ?g weekly and ribavirin 600 mg daily, followed by a further 36 weeks of pegylated interferon and ribavirin alone and 24 weeks of follow-up. Efficacy (sustained virological response [SVR] 12 weeks after last planned study dose), safety and tolerability of telaprevir throughout the study were assessed. Pharmacokinetics of telaprevir, tacrolimus and cyclosporin A were also examined.
  
  
  RESULTS
  In total, 74 patients were recruited. Overall, 72% (53/74; 95% CI: 59.9 to 81.5) of patients achieved SVR at 12 weeks following completion of treatment. Anticipated increases in plasma concentrations of tacrolimus and cyclosporin A occurred during telaprevir treatment and were successfully managed through immunosuppressant dose reduction and, for tacrolimus, reduced dosing frequency. Safety and tolerability of telaprevir-based triple therapy were generally comparable with previous data in non-transplant patients, although rates of reported anemia (55% [41/74]) were higher. Elevated plasma creatinine (46% [34/74]) was observed during REPLACE - consistent with the post-liver transplant population and the co-administered immunosuppressants.
  
  
  CONCLUSIONS
  Telaprevir-based triple therapy in patients with recurrent genotype 1 HCV infection following liver transplantation produced high rates of SVR. Therapeutic concentrations of immunosuppressants were maintained successfully through dose modification during telaprevir treatment.
authors.affiliation: Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Centre Hepatobiliaire, Hospital Paul Brousse, University Paris South Villejuif, Paris, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Didier
authors.affiliation: Queen Elizabeth Hospital and NIHR BRU, Birmingham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Mutimer
authors.affiliation: Gastroenterology and Transplant Hepatology Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fagiuoli
authors.affiliation: Liver Unit, Hospital Clinic, CIBEREHD and IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Navasa
authors.affiliation: Kings College Hospital, London, UK.
authors.forename: Kosh
authors.initials: K
authors.lastname: Agarwal
authors.affiliation: La Fe University Hospital and Ciberehd, Valencia, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Berenguer
authors.affiliation: Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Universita degli Studi di Milano, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Department of General, Visceral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
authors.affiliation: University Hospitals KU Leuven, Leuven, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Nevens
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Daems
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Janssen
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Sivi
authors.initials: S
authors.lastname: Ouwerkerk-Mahadevan
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Kimko
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Erkki
authors.initials: E
authors.lastname: Lathouwers
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Witek
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Rodica
authors.initials: R
authors.lastname: Van Solingen-Ristea
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000517:prevention & control; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007372:Interferons / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D012367:RNA, Viral; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; D016572:Cyclosporine; D007372:Interferons; D016559:Tacrolimus