title: Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.
abstract: OBJECTIVE
  Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75-80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens.
  
  
  METHODS
  A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5 years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs).
  
  
  RESULTS
  Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of $15,709/QALY at baseline cost of oral therapy. The ICER remained below $50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease.
  
  
  CONCLUSIONS
  Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Betty & Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA. Electronic address: zobair.younossi@inova.org.
authors.forename: Zobair M
authors.initials: ZM
authors.lastname: Younossi
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Mendel E
authors.initials: ME
authors.lastname: Singer
authors.affiliation: Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Betty & Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
authors.forename: Heshaam M
authors.initials: HM
authors.lastname: Mir
authors.affiliation: Betty & Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Henry
authors.affiliation: Betty & Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Hunt
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000191:economics; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination / Q000191:economics; D005838:Genotype; D017048:Health Care Costs; D016174:Hepacivirus / Q000145:classification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b
keywords: BOC; CHC; CMS; Centers for Medicare and Medicaid Services; Cost-effectiveness analysis; DAA; F0, F1; F2 or F4; GT; HCV; HIV; ICER; IFN; IFN, BV, DAA; Interferon-free oral treatment; Markov model; NADAC; National Average Drug Acquisition Cost; QALYs; RBV; SVR; TVR; Triple therapy; WAC; boceprevir; chronic hepatitis C; direct, acting antiviral agent; genotype; hepatitis C; immunodeficiency virus; incremental cost, effectiveness analysis; mild fibrosis; moderate or advanced fibrosis; pegylated, interferon alpha; quality, adjusted life years (a standard metric that incorporates both length and quality of life); ribavirin; sustained virologic response; telaprevir; wholesale acquisition cost