Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver Transplantation: The Phase II SATURN study

TY - JOUR

T1 - Efficacy, safety, and pharmacokinetics of simeprevir, daclatasvir, and ribavirin in patients with recurrent hepatitis C virus genotype 1b infection after orthotopic liver Transplantation: The Phase II SATURN study

AU - Forns, Xavier

AU - Berenguer, Marina

AU - Herzer, Kerstin

AU - Sterneck, Martina

AU - Donato, Maria Francesca

AU - Andreone, Pietro

AU - Fagiuoli, Stefano

AU - Cieciura, Tomasz

AU - Durlik, Magdalena

AU - Calleja, Jose Luis

AU - Mariño, Zoe

AU - Shukla, Umesh

AU - Verbinnen, Thierry

AU - Lenz, Oliver

AU - Ouwerkerk-Mahadevan, Sivi

AU - Peeters, Monika

AU - Janssen, Katrien

AU - Kalmeijer, Ronald

AU - Jessner, Wolfgang

N1 - © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2017/6

Y1 - 2017/6

N2 - BACKGROUND: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival.METHODS: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT).RESULTS: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended.CONCLUSION: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.

AB - BACKGROUND: Recurrent hepatitis C virus (HCV) infection following liver transplantation is associated with accelerated progression to graft failure and reduced patient survival.METHODS: The Phase II, open-label SATURN study (NCT01938625) investigated the combination of simeprevir (SMV), daclatasvir (DCV), and ribavirin (RBV) administered for 24 weeks in 35 patients with recurrent HCV genotype (GT) 1b infection after orthotopic liver transplantation (OLT).RESULTS: High rates of both on-treatment and sustained virologic response 12 weeks after end of treatment (SVR12) were achieved in patients who were either treatment-naïve or had failed post-OLT treatment with peginterferon and RBV. Overall, 91% of patients (32/35) achieved SVR12. The combination was generally well tolerated, with an adverse event profile consistent with that observed in previous clinical trials of SMV or DCV separately. Co-administration of SMV with cyclosporine resulted in significantly increased SMV plasma exposures, which was not the case with the co-administration of SMV with tacrolimus. Therefore, the concomitant use of SMV with cyclosporine is not recommended.CONCLUSION: The interferon-free combination of SMV, DCV, and RBV administered for 24 weeks was shown to be effective and well tolerated in the treatment of post-OLT HCV GT1b-infected patients.

KW - Journal Article

U2 - 10.1111/tid.12696

DO - 10.1111/tid.12696

M3 - SCORING: Journal article

C2 - 28295849

VL - 19

SP - UNSP e12696

JO - TRANSPL INFECT DIS

JF - TRANSPL INFECT DIS

SN - 1398-2273

IS - 3

ER -