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2016, Number 4

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Ann Hepatol 2016; 15 (4)

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

Forns X, Samuel D, Mutimer D, Fagiuoli S, Navasa M, Agarwal K, Berenguer M, Colombo M, Herzer K, Nevens F, Daems B, Janssen K, Ouwerkerk-Mahadevan S, Kimko H, Lathouwers E, Witek J, Solingen-Ristea RV

Language: English
References: 40
Page: 512-523
PDF size: 348.91 Kb.


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.


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