OBJECTIVE: In the Phase 3 study REALIZE, the addition of telapre-vir (TVR, T) in combination with peginterferon alfa-2a/ribavirin(PR) for the treatment of genotype 1 chronic HCV infection in treatment-experienced patients substantially increased SVR com-pared to PR alone. Based on this improvement in SVR rates, an Excel®-based decision-analytic model was used to explore the potential long-term clinical value of TVR-based therapy in REAL-IZE patients who were prior relapsers, partial responders, and null responders to a prior course of PR.
METHODS: A two-part(Treatment; Post-Treatment) model was developed to project ALD-related clinical outcomes of 3 treatment options: T/PR, PR,and no treatment. For the Treatment part, parallel hypothetical cohorts of 1,000 patients were created and assigned to the three treatment options. Based on REALIZE intention-to-treat SVR rates, a proportion of each cohort was deemed to achieve SVR. Cohorts were directed into the Post-Treatment part where long-term treatment consequences were estimated for remaining life-times using a cyclic Markov process. In any cycle, patients could remain in or transition among mutually exclusive health states: pre-cirrhosis, cirrhosis, decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplantation (LT), and death. Baseline patient characteristics and SVR rates by base-line fibrosis score were based on REALIZE data. Age- and gender-specific health state transition probabilities, which varied with achievement of SVR, and mortality were obtained from published literature.
RESULTS: The model estimated that T/PR substantially improved HCV-related complications (Table) and life expectancy across all groups. Prior relapsers, partial responders, and null responders treated with T/PR were projected to live 5.5, 3.5, and 2.4 yrs longer, respectively, compared to no treatment. PR improved life expectancies by a projected 1.3,0.8, and 0.4 yrs compared to no treatment.
CONCLUSION: Modeling results suggested that higher rates of sustained virologic response will yield substantial improvements in lifetime clinical outcomes in all treatment-experienced groups.
