Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study

Abstract

Background: SPRINT-2 demonstrated that boceprevir (BOC), an oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor, added to peginterferon alfa-2b (P) and ribavirin (R) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1. We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation.

Methods: A Markov model was used to estimate the incidence of liver complications, discounted costs (2010 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of three treatment strategies for treatment-naïve patients with chronic HCV genotype 1. The model simulates the treatment regimens studied in SPRINT-2 in which PR was administered for 4 weeks followed by: 1) placebo plus PR for 44 weeks (PR48); 2) BOC plus PR using response guided therapy (BOC/RGT); and 3) BOC plus PR for 44 weeks (BOC/PR48) and makes projections within and beyond the trial. HCV-related state-transition probabilities, costs, and utilities were obtained from previously published studies. All costs and QALYs were discounted at 3%.

Results: The model projected approximately 38% and 43% relative reductions in the lifetime incidence of liver complications in the BOC/RGT and BOC/PR48 regimens compared with PR48, respectively. Treatment with BOC/RGT is associated with an incremental cost of $10,348 and an increase of 0.62 QALYs compared to treatment with PR48. Treatment with BOC/PR48 is associated with an incremental cost of $35,727 and an increase of 0.65 QALYs compared to treatment with PR48. The ICERs were $16,792/QALY and $55,162/QALY for the boceprevir-based treatment groups compared with PR48, respectively. The ICER for BOC/PR48 compared with BOC/RGT was $807,804.

Conclusion: The boceprevir-based regimens used in the SPRINT-2 trial were projected to substantially reduce the lifetime incidence of liver complications and increase the QALYs in treatment-naive patients with hepatitis C genotype 1. It was also demonstrated that boceprevir-based regimens offer patients the possibility of experiencing great clinical benefit with a shorter duration of therapy. Both boceprevir-based treatment strategies were projected to be cost-effective at a reasonable threshold in the US when compared to treatment with PR48.

Trial registration: ClinicalTrials.gov NCT00705432.

Figure 1

Schematic Diagram of HCV Therapy and Disease Progression. Y – yes; N – no; Tx – treatment; ETR – end of treatment response; SVR – sustained virologic response; F0 – no fibrosis; F1 – portal fibrosis without septa; F2 – portal fibrosis with few septa; F3 – numerous septa without cirrhosis; F4 – cirrhosis; DC – decompensated cirrhosis; HCC – hepatocellular carcinoma; LT – liver transplantation; PLT – post-liver transplantation; Lv-death – liver-related death.

Figure 2

Cumulative risk of developing HCV liver-related complications, by SPRINT-2 Treatment Strategy, over time. DC – decompensated cirrhosis; HCC – hepatocellular carcinoma; LT – liver transplantation; LD – liver-related death; PR48 – peginterferon-ribavirin regimen for 48 weeks; BOC/RGT – peginterferon-ribavirin and boceprevir for 24 weeks, and those with a detectable hepatitis C virus (HCV) RNA level between weeks 8 and 24 received peginterferon–ribavirin from week 28 to week 48; BOC/PR48 –peginterferon–ribavirin for 48 weeks and boceprevir for 44 weeks.

Figure 3

Cost-effectiveness acceptability curve of SPRINT-2 treatment strategies. BOC/RGT vs. PR48 and BOC/PR48 vs. PR48. PR48 – peginterferon-ribavirin regimen for 48 weeks; BOC/RGT – peginterferon-ribavirin and boceprevir for 24 weeks, and those with a detectable hepatitis C virus (HCV) RNA level between weeks 8 and 24 received peginterferon–ribavirin from week 28 to week 48; BOC/PR48 –peginterferon–ribavirin for 48 weeks and boceprevir for 44 weeks.

Figure 4

Cost-effectiveness frontier of SPRINT-2 treatment strategies. BOC/RGT vs. PR48 and BOC/PR48 vs. PR48 for all patients and by race cohort. PR48 – peginterferon-ribavirin regimen for 48 weeks; BOC/RGT – peginterferon-ribavirin and boceprevir for 24 weeks, and those with a detectable hepatitis C virus (HCV) RNA level between weeks 8 and 24 received peginterferon–ribavirin from week 28 to week 48; BOC/PR48 –peginterferon–ribavirin for 48 weeks and boceprevir for 44 weeks.