Efficacy of telaprevir dosed twice daily versus every 8 hours by IL28B genotype: Results from the phase iii optimize study.

Background and Aims: OPTIMIZE established the non-inferior efficacy of telaprevir (TVR, T) twice daily (bid) versus every 8 hours (q8h) in combination with peginterferon/ribavirin (PR) across a range of patient characteristics. One stratification factor of the study was IL28B genotype. Here we provide detailed characterization of study results across IL28B genotype groups. Method(s): OPTIMIZE was a randomized, open-label, multicenter, Phase III trial in treatment-naive patients with chronic HCV genotype 1 infection (NCT01241760). In total, 740 patients were stratified by IL28B genotype (CC, CT, TT) and liver fibrosis stage (F0-F2 vs F3/F4), and randomized to either TVR 1125mg bid (N = 369) or TVR 750mg q8h (N = 371) in combination with PR. (Table presented) Results: The percentage of patients by IL28B genotype was: CC=29%, CT=56%, TT=16%. Genotype distribution was balanced equally by treatment arm (Table). Based on multivariate analysis, female sex, black race, lower baseline (BL) HCV viral load (VL), and cirrhosis were significantly associated with lower odds of CC genotype. The efficacy of TVR bid versus q8h was similar regardless of IL28B genotype (Figure). SVR12 was higher in CC versus non-CC genotypes (90% vs 67%, p < 0.0001). IL28B CC genotype was strongly associated with SVR12 after adjustment for other baseline factors, including fibrosis stage (OR = 5.00, 95% CI: 3.01, 8.30; p < 0.0001). When IL28B and fibrosis stage were considered together, the highest SVR12 (90%, 95% CI: 84%, 94%) was observed in CC patients with F0-F2 fibrosis stage, while the lowest SVR12 (47%, 95% CI: 39%, 56%) was observed in non-CC patients with advanced fibrosis or cirrhosis (F3-F4). Conclusion(s): Black patients, women, and patients with cirrhosis were less likely to have IL28B CC genotype. SVR12 was higher in patients with CC vs non-CC genotypes, with the highest absolute efficacy observed in genotype CC patients with F0-F2 fibrosis. Although IL28B CC genotype is a positive predi