Efficacy of telaprevir-based therapy in stable liver transplant patients with chronic genotype 1 hepatitis C

Xavier Forns, Didier Samuel, David Mutimer, Stefano Fagiuoli, Miquel Navasa, Kosh Agarwal, Marina Berenguer, Massimo Colombo, Kerstin Herzer, Frederik Nevens, Bjorn Daems, Katrien Janssen, Sivi Ouwerkerk-Mahadevan, Holly Kimko, Erkki Lathouwers, James Witek, Rodica van Solingen-Ristea

Research output: Contribution to journalArticlepeer-review

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 μg 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. Conclusion. 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.

Original languageEnglish
Pages (from-to)512-523
Number of pages12
JournalAnnals of Hepatology
Volume15
Issue number4
Publication statusPublished - Jul 1 2016

Keywords

  • Hepatitis C infection
  • Liver transplant
  • Telaprevir

ASJC Scopus subject areas

  • Hepatology

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