Z Gastroenterol 2013; 51 - K108
DOI: 10.1055/s-0033-1352748

Safety and efficacy of twice daily versus every 8 hour telaprevir with Peginterfepon/Ribavirin (PR) in patients with cirrhosis

P Buggisch 1, YJ Horsmans 2, RS Brown 3, M Buti 4, K Agarwal 5, W Sievert 6, E Janczewska 7, C Hezode 8, M Rizzetto 9, R Parana 10, S De Meyer 11, R De Masi 12, D Luo 12, J Witek 12, S Zeuzem 13
  • 1IFI-Institut für interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg, Germany
  • 2Cliniques Universitaires Saint-Luc, Brussels, Belgium
  • 3Columbia University College, New York, United States
  • 4Hospital Valle Hebron and Ciberehd del Institut, Barcelona, Spain
  • 5King's College Hospital, London, United Kingdom
  • 6Monash Medical Centre and Monash University, Melbourne, Australia
  • 7Outpatients Clinic for Hepatology, Myslowice, Poland
  • 8Hopital Henri Mondor, Creteil, France
  • 9University of Torino, Torino, Italy
  • 10Medical School, Bahia, Brazil
  • 11Janssen Infectious Diseases, Beerse, Belgium
  • 12Janssen Research & Development LLC, Titusville, United States
  • 13Klinikum der J. W. Goethe-Universität, Frankfurt am Main, Germany

Aims: Non-inferior efficacy of telaprevir (TVR) twice-daily (bid) versus every 8 hours (q8h), in combination with peginterferon/ribavirin (PR) in treatment-naïve patients, has been established across a range of patient baseline characteristics. Here we describe detailed results of TVR bid or q8h across fibrosis/cirrhosis stages.

Methods: OPTIMIZE was a randomized, open-label, multicenter, Phase III trial in treatment-naïve patients with chronic HCV genotype 1 infection (NCT01241760). Patients were stratified by liver fibrosis stage (F0-F2 vs. F3/4) and IL28B genotype, and randomized to either TVR 1125 mg bid (N = 369) or 750 mg q8h (N = 371). The primary endpoint was sustained virologic response (SVR12; HCV RNA < 25 IU/mL 12 weeks after last planned dose of PR). Fibrosis stage was assessed by liver biopsy.

Results: 529 (71%) patients were fibrosis stage F0-F2 and 210 (29%) were fibrosis stage F3/4: 103 (14%) patients had cirrhosis (F4). Virologic response rates between TVR bid and q8h treatment groups were generally comparable within fibrosis stage and cirrhosis subgroups (Table). 56/103 (54%) patients with cirrhosis attained RVR (undetectable HCV RNA at week 4) and were treated for a total of 24 weeks. Of these 51/56 (91%) achieved eRVR (undetectable HCV RNA at weeks 4 and 12) and of these 51 patients 36 (71%) achieved SVR.

Grade 3 or 4 adverse events (AEs) were reported in 41% (42/103) of patients with and 40% (252/636) of patients without cirrhosis (TVR phase). Serious adverse events (SAEs) and TVR discontinuations due to AEs occurred in 14% (14/103) and 21% (22/103) of patients with cirrhosis, and 8% (48/636) and 16% (104/636) of those without, respectively. Total incidences of rash and anemia events were similar for patients with and without cirrhosis (rash: 50% vs. 53%, respectively; anemia: 50% vs. 44%, respectively).

Conclusions: The relative efficacy of TVR bid versus q8h was similar regardless of fibrosis/cirrhosis stage, offering the potential of simplified TVR dosing to all patients, including