Xavier Forns1, Marina Berenguer2, Kerstin Herzer3, Martina Sterneck4, Maria Francesca Donato5, Pietro Andreone6, Stefano Fagiuoli7, Tomasz Cieciura8, Magdalena Durlik9, Jose Luis Calleja10, Zoe Mariño1, Umesh Shukla11, Thierry Verbinnen12, Oliver Lenz12, Sivi Ouwerkerk-Mahadevan13, Monika Peeters12, Katrien Janssen12, Ronald Kalmeijer11, Wolfgang Jessner11. 1. Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, University of Barcelona, Barcelona, Spain. 2. Department of Digestive Diseases, Hepatology and Liver Transplantation Unit, La Fe University Hospital and CIBEREHD, Valencia, Spain. 3. Department of General, Visceral and Transplantation Surgery and Department of Gastroenterology and Hepatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. 4. Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 5. Division of Digestive Diseases, IRCCS Maggiore Hospital, Milan, Italy. 6. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 7. Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy. 8. Department of Immunology, Transplant Medicine and Internal Diseases, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland. 9. Department of Transplantation Medicine and Nephrology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland. 10. Liver Unit, Hospital Universitario Puerta de Hierro, CIBEREHD and IDIPHIM, Madrid, Spain. 11. Janssen Research & Development, LLC, Titusville, NJ, USA. 12. Janssen Pharmaceutica NV, Beerse, Belgium. 13. Janssen Research & Development, Beerse, Belgium.
Abstract
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.
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.
Authors: Roberto Minutolo; Alessio Aghemo; Antonio Chirianni; Fabrizio Fabrizi; Loreto Gesualdo; Edoardo G Giannini; Paolo Maggi; Vincenzo Montinaro; Ernesto Paoletti; Marcello Persico; Francesco Perticone; Salvatore Petta; Massimo Puoti; Giovanni Raimondo; Maria Rendina; Anna Linda Zignego Journal: Intern Emerg Med Date: 2018-09-25 Impact factor: 3.397
Authors: Fiona Marra; Christoph Höner Zu Siederdissen; Saye Khoo; David Back; Michael Schlag; Sivi Ouwerkerk-Mahadevan; Ceyhun Bicer; Isabelle Lonjon-Domanec; Wolfgang Jessner; Maria Beumont-Mauviel; Ronald Kalmeijer; Markus Cornberg Journal: Br J Clin Pharmacol Date: 2018-02-21 Impact factor: 4.335