title: Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.
abstract: BACKGROUND
  The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80% to 95%, though with a substantial increase in cost. In particular, current market pricing of a 12-week course of sofosbuvir is approximately US$84,000. We determine the cost-effectiveness of new treatments in comparison with the standard care of treatments.
  
  
  METHODS
  A Markov simulation model of CHC disease progression is used to evaluate the cost-effectiveness of different treatment strategies based on genotype. The model calculates the expected lifetime medical costs and quality adjusted life years (QALYs) of hypothetical cohorts of identical patients receiving certain treatments. For genotype 1, we compare: (1) peginterferon + ribavirin + telaprevir for 12 weeks, followed by 12 or 24 weeks treatment of peginterferon + ribavirin dependent on HCV RNA level at week 12; (2) Harvoni treatment, 12 weeks; (3) Olysio + Sovaldi, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (4) Viekira Pak + ribavirin, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (5) sofosbuvir + peginterferon + ribavirin, 12 weeks for patients with or without cirrhosis. For genotypes 2 and 3, treatment strategies include: (1) peginterferon + ribavirin, 24 weeks for treatment-naïve patients; (2) sofosbuvir + ribavirin, 12 weeks for patients with genotype 2, 24 weeks for genotype 3; (3) peginterferon + ribavirin as initial treatment, 24 weeks for patients with genotype 2/3, follow-up treatment with sofosbuvir + ribavirin for 12/16 weeks are performed on non-responders and relapsers.
  
  
  RESULTS
  Viekira Pak is cost-effective for genotype 1 patients without cirrhosis, whereas Harvoni is cost-effective for genotype 1 patients with cirrhosis. Sofosbuvir-based treatments for genotype 1 in general are not cost-effective due to its substantial high costs. Two-phase treatments with 12-week and 16-week follow-ups are cost-effective for genotype 3 patients and for genotype 2 patients with cirrhosis. The results were shown to be robust over a broad range of parameter values through sensitivity analysis.
  
  
  CONCLUSIONS
  For genotype 1, sofosbuvir-based treatments are not cost-effective compared to Viekira Pak and Harvoni, although a 30% reduction in sofosbuvir price would change this result. Sofosbuvir + ribavirin are cost-effective as second-phase treatments following peginterferon + ribavirin initial treatment for genotypes 2 and 3. However, there is limited data on sofosbuvir-involved treatment, and the results obtained in this study must be interpreted within the model assumptions.
authors.affiliation: Department of Industrial Engineering, Penn State University, University Park, PA, 16803, USA. swz5073@psu.edu.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Industrial Engineering, Penn State University, University Park, PA, 16803, USA. ndbastian@psu.edu.
authors.forename: Nathaniel D
authors.initials: ND
authors.lastname: Bastian
authors.affiliation: School of Industrial and Systems Engineering, Georgia Institute of Technology, 755 Ferst Dr, Atlanta, GA, 30332-0205, USA. pgriffin@gatech.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Griffin
mesh_terms: D000998:Antiviral Agents / Q000191:economics* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000191:economics / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000191:economics; D005260:Female; D005449:Fluorenes / Q000191:economics / Q000627:therapeutic use; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000191:economics / Q000627:therapeutic use; D047028:Macrocyclic Compounds / Q000191:economics / Q000627:therapeutic use; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D012254:Ribavirin / Q000191:economics / Q000627:therapeutic use; D019438:Ritonavir / Q000191:economics / Q000627:therapeutic use; D000069616:Simeprevir / Q000191:economics / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000191:economics* / Q000627:therapeutic use; D013449:Sulfonamides / Q000191:economics / Q000627:therapeutic use; D014498:Uracil / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D005449:Fluorenes; D047028:Macrocyclic Compounds; D013449:Sulfonamides; C000607373:Viekira Pak; C000595958:ledipasvir, sofosbuvir drug combination; D011092:Polyethylene Glycols; D012254:Ribavirin; D014498:Uracil; D007372:Interferons; D000069616:Simeprevir; D014542:Uridine Monophosphate; D019438:Ritonavir; D000069474:Sofosbuvir