title: Twice-Daily Telaprevir for Posttransplant Genotype 1 Hepatitis C Virus: A Prospective Safety, Efficacy, and Pharmacokinetics Study.
abstract: OBJECTIVE
  Our objective was to determine the safety, efficacy, and pharmacokinetics of telaprevir plus pegylated interferon alfa 2a and ribavirin for chronic, posttransplant genotype 1 hepatitis C virus infection.
  
  
  METHODS
  A prospective, single-arm, multicenter, open-label, phase 2b study was conducted at 22 North American sites to assess the safety, efficacy, and pharmacokinetics of pegylated interferon alfa 2a, ribavirin, and twice daily telaprevir in liver transplant recipients with recurrent, chronic hepatitis C without cirrhosis. Baseline liver biopsies were read by a central pathologist. There were planned safety reviews after a sentinel cohort reached treatment weeks 4 and 16. Serial pharmacokinetic sampling was performed for calcineurin inhibitors, telaprevir, and ribavirin.
  
  
  RESULTS
  Sixty-one patients were enrolled and received ≥ 1 dose of study medication; 37 (61%) achieved sustained virologic response. Thirteen of 18 treatment-naive patients (72%), 10 of 11 patients with no or minimal fibrosis (91%), 13 of 15 patients (87%) with interleukin 28B genotype CC, and 36 of 45 patients (80%) with either undetectable or unquantifiable hepatitis C virus RNA at treatment week 4 achieved sustained virologic response. Nine patients (15%) had ≥ 1 drug-related serious adverse event and 7 (11%) discontinued all study drugs due to an adverse event. There were no deaths or acute cellular rejection episodes. During telaprevir treatment, median doses of tacrolimus and cyclosporine were 0.5 mg weekly and 25 mg daily. Target exposures were achieved for telaprevir with twice daily dosing and for ribavirin with reduced initial dosing.
  
  
  CONCLUSIONS
  Telaprevir combination therapy for posttransplant hepatitis C virus infection yielded superior efficacy than historical controls. Adverse events were similar to, but exceeded, those in immunocompetent patients. Calcineurin inhibitor dosing levels were substantially reduced with telaprevir.
authors.affiliation: From the Piedmont Transplant Institute, Piedmont Hospital, Atlanta, Georgia, USA.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Rubin
authors.forename: Mark W
authors.initials: MW
authors.lastname: Russo
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Brown
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Josh
authors.initials: J
authors.lastname: Levitsky
authors.forename: Hugo
authors.initials: H
authors.lastname: Vargas
authors.forename: Eric M
authors.initials: EM
authors.lastname: Yoshida
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D016898:Interferon-alpha / Q000008:administration & dosage; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009656:North America; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D010641:Phenotype; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D000072230:Sustained Virologic Response; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C100416:peginterferon alfa-2a