Cost‐effectiveness of new antiviral regimens for treatment‐naïve U.S. veterans with hepatitis C

Recently approved, interferon‐free medication regimens for treating hepatitis C are highly effective, but extremely costly. We aimed to identify cost‐effective strategies for managing treatment‐naïve U.S. veterans with new hepatitis C medication regimens. We developed a Markov model with 1‐year cycle length for a cohort of 60‐year‐old veterans with untreated genotype 1 hepatitis C seeking treatment in a typical year. We compared using sofosbuvir/ledipasvir or ombitasvir/ritonavir/paritaprevir/dasabuvir to treat: (1) any patient seeking treatment; (2) only patients with advanced fibrosis or cirrhosis; or (3) patients with advanced disease first and healthier patients 1 year later. The previous standard of care, sofosbuvir/simeprevir or sofosbuvir/pegylated interferon/ribavirin, was included for comparison. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die. Complications were less likely after sustained virological response. We calculated the incremental cost per quality‐adjusted life year (QALY) and varied model inputs in one‐way and probabilistic sensitivity analyses. We used the Veterans Health Administration perspective with a lifetime time horizon and 3% annual discounting. Treating any patient with ombitasvir‐based therapy was the preferred strategy ($35,560; 14.0 QALYs). All other strategies were dominated (greater costs/QALY gained than more effective strategies). Varying treatment efficacy, price, and/or duration changed the preferred strategy. In probabilistic sensitivity analysis, treating any patient with ombitasvir‐based therapy was cost‐effective in 70% of iterations at a $50,000/QALY threshold and 65% of iterations at a $100,000/QALY threshold. Conclusion: Managing any treatment‐naïve genotype 1 hepatitis C patient with ombitasvir‐based therapy is the most economically efficient strategy, although price and efficacy can impact cost‐effectiveness. It is economically unfavorable to restrict treatment to patients with advanced disease or use a staged treatment strategy. (Hepatology 2016;63:428–436)

[1]  Eoin Coakley,et al.  Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. , 2014, The New England journal of medicine.

[2]  Brian L. Pearlman,et al.  Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study , 2014, The Lancet.

[3]  R. Cheung,et al.  Implications of rapid virological response in hepatitis C therapy in the US veteran population , 2012, Alimentary pharmacology & therapeutics.

[4]  D. Harnois,et al.  Aging of Hepatitis C Virus (HCV)-Infected Persons in the United States: A Multiple Cohort Model of HCV Prevalence and Disease Progression , 2010 .

[5]  Thomas Berg,et al.  ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. , 2014, The New England journal of medicine.

[6]  P. Terasaki,et al.  Liver transplantation in the United States. , 2005, Clinical transplants.

[7]  Dieter Häussinger,et al.  Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. , 2002, The New England journal of medicine.

[8]  Peter J. Richardson,et al.  Gaps in the achievement of effectiveness of HCV treatment in national VA practice. , 2012, Journal of hepatology.

[9]  William M. Lee,et al.  A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C , 2011, Hepatology.

[10]  S. Pol,et al.  FIB‐4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest , 2007, Hepatology.

[11]  A. Butt,et al.  Effect of hepatitis C virus and its treatment on survival , 2009, Hepatology.

[12]  J. R. Scotti,et al.  Available From , 1973 .

[13]  M. Manns,et al.  Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. , 2012, JAMA.

[14]  L. Henry,et al.  Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients. , 2014, Journal of hepatology.

[15]  D. Thompson,et al.  The burden of illness associated with hepatocellular carcinoma in the United States. , 2009, Journal of hepatology.

[16]  A. Flaxman,et al.  Global epidemiology of hepatitis C virus infection: New estimates of age‐specific antibody to HCV seroprevalence , 2013, Hepatology.

[17]  T. Brennan,et al.  Cost-Effectiveness of Novel Regimens for the Treatment of Hepatitis C Virus , 2015, Annals of Internal Medicine.

[18]  B. Luxon,et al.  Limited success of HCV antiviral therapy in United States veterans , 2002, American Journal of Gastroenterology.

[19]  S. Holmberg,et al.  Limited Access to New Hepatitis C Virus Treatment Under State Medicaid Programs , 2015, Annals of Internal Medicine.

[20]  B. McNeil,et al.  Probabilistic Sensitivity Analysis Using Monte Carlo Simulation , 1985, Medical decision making : an international journal of the Society for Medical Decision Making.

[21]  S. Saab,et al.  Timing of hepatitis C antiviral therapy in patients with advanced liver disease: A decision analysis model , 2010, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[22]  P. Thuras,et al.  All-Cause Mortality and Liver-Related Outcomes Following Successful Antiviral Treatment for Chronic Hepatitis C , 2014, Digestive Diseases and Sciences.

[23]  G. Davis,et al.  Projecting future complications of chronic hepatitis C in the United States , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[24]  Sprint Investigators,et al.  Boceprevir for Untreated Chronic HCV Genotype 1 Infection , 2011 .

[25]  Y. Yazdanpanah,et al.  Should we await IFN-free regimens to treat HCV genotype 1 treatment-naive patients? A cost-effectiveness analysis (ANRS 95141). , 2014, Journal of hepatology.

[26]  Va Puget Elevated prevalence of hepatitis C infection in users of United States veterans medical centers , 2005 .

[27]  M. Gold Cost-effectiveness in health and medicine , 2016 .

[28]  A. Borkowski,et al.  Hepatitis C genotype analysis: results in a large veteran population with review of the implications for clinical practice. , 2012, Annals of clinical and laboratory science.

[29]  Nathaniel D. Bastian,et al.  Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US , 2015, BMC Gastroenterology.

[30]  R. Wolfe,et al.  Trends in Organ Donation and Transplantation in the United States, 1996–2005 , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[31]  Robert Herring,et al.  Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. , 2014, The New England journal of medicine.

[32]  John McNally,et al.  Sofosbuvir for previously untreated chronic hepatitis C infection. , 2013, The New England journal of medicine.

[33]  R. Schinazi,et al.  Cost analysis of sofosbuvir/ribavirin versus sofosbuvir/simeprevir for genotype 1 hepatitis C virus in interferon‐ineligible/intolerant individuals , 2014, Hepatology.

[34]  P. Heagerty,et al.  Elevated prevalence of hepatitis C infection in users of United States veterans medical centers , 2005, Hepatology.

[35]  E. Schiff,et al.  Hepatitis C virus infection in USA: an estimate of true prevalence , 2011, Liver international : official journal of the International Association for the Study of the Liver.

[36]  Peter G. Stock,et al.  OPTN/SRTR 2011 Annual Data Report: Liver , 2013, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[37]  M. Stepanova,et al.  Minimal impact of sofosbuvir and ribavirin on health related quality of life in chronic hepatitis C (CH-C). , 2014, Journal of hepatology.

[38]  M. Manns,et al.  Boceprevir for untreated chronic HCV genotype 1 infection. , 2011, The New England journal of medicine.

[39]  S. Asch,et al.  Cost-Effectiveness Analysis of Direct-Acting Antiviral Therapy for Treatment-Naïve Patients with Chronic Hepatitis C Genotype 1 Infection in the Veterans Health Administration , 2013 .

[40]  M. Golden,et al.  Cost-effectiveness and population outcomes of general population screening for hepatitis C. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[41]  T. Hassanein,et al.  Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial , 2013, The Lancet.

[42]  J. Chhatwal,et al.  The Changing Burden of Hepatitis C Virus Infection in the United States: Model-Based Predictions , 2014, Annals of Internal Medicine.

[43]  M. Stepanova,et al.  Patient‐reported outcomes in chronic hepatitis C patients with cirrhosis treated with sofosbuvir‐containing regimens , 2014, Hepatology.

[44]  J. Kaldor,et al.  Estimation of Utilities for Chronic Hepatitis C from SF-36 Scores , 2005, The American Journal of Gastroenterology.

[45]  G. Dore,et al.  Estimation of stage‐specific fibrosis progression rates in chronic hepatitis C virus infection: A meta‐analysis and meta‐regression , 2008, Hepatology.

[46]  Stefan Zeuzem,et al.  Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. , 2014, The New England journal of medicine.

[47]  Aijaz Ahmed,et al.  Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. , 2015, Gastroenterology.

[48]  R. Wolfe,et al.  Trends in Organ Donation and Transplantation in the United States, 1999–2008 , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[49]  R. Marinho,et al.  ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. , 2014, The New England journal of medicine.

[50]  R. Solá,et al.  Natural history of decompensated hepatitis C virus-related cirrhosis. A study of 200 patients. , 2004, Journal of hepatology.

[51]  A. Bhalla,et al.  Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. , 1997, Gastroenterology.

[52]  S. El-Kamary,et al.  All-cause, liver-related, and non-liver-related mortality among HCV-infected individuals in the general US population. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[53]  G. Foster,et al.  Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection , 2010, Alimentary pharmacology & therapeutics.

[54]  J. Hanmer Predicting an SF-6D preference-based score using MCS and PCS scores from the SF-12 or SF-36. , 2009, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[55]  R. Schinazi,et al.  All‐oral, interferon‐free treatment for chronic hepatitis C: cost‐effectiveness analyses , 2013, Journal of viral hepatitis.

[56]  M. Roberts,et al.  What Does the Value of Modern Medicine Say About the $50,000 per Quality-Adjusted Life-Year Decision Rule? , 2008, Medical care.

[57]  J J Fung,et al.  Liver Transplantation in the United States, 1999–2008 , 2010, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.