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