The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus.

BACKGROUND New hepatitis C virus (HCV) treatments deliver higher cure rates with fewer contraindications, increasing demand for treatment and healthcare costs. The cost-effectiveness of new treatments is unknown. METHODS We conducted a microsimulation of guideline testing followed by alternative treatment regimens for HCV among the US population aged 20 and older to estimate cases identified, treated, sustained viral response, deaths, medical costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different treatment options expressed as discounted lifetime costs and benefits from the healthcare perspective. RESULTS Compared to treatment with pegylated interferon and ribavirin (PR), and a protease inhibitor for HCV genotype (G) 1 and PR alone for G2/3, treatment with PR and Sofosbuvir (PRS) for G1/4 and treatment with Sofosbuvir and ribavirin (SR) for G2/3 increased QALYs by 555 226, reduced deaths by 80 682, and increased costs by $26.2 billion at an ICER of $47 304 per QALY gained. As compared to PRS/SR, treating with an all oral regimen of Sofosbuvir and Simeprevir (SS) for G1/4 and SR for G2/3, increased QALYs by 1 110 451 and reduced deaths by an additional 164 540 at an incremental cost of $80.1 billion and an ICER of $72 169. In sensitivity analysis, where treatment with SS effectiveness was set to the list price of Viekira Pak and then Harvoni, treatment cost $24 921 and $25 405 per QALY gained as compared to PRS/SR. CONCLUSIONS New treatments are cost-effectiveness per person treated, but pent-up demand for treatment may create challenges for financing.

[1]  Bryce D. Smith,et al.  Eradication of Hepatitis C Virus Infection and the Development of Hepatocellular Carcinoma , 2013, Annals of Internal Medicine.

[2]  Rebecca L Morgan,et al.  Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. , 2012, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[3]  R. Kamel AASLD 2016 Recommendations for Testing, Managing, and Treating Hepatitis C , 2017 .

[4]  A Jakins,et al.  The cost of hepatitis A infections in American adolescents and adults in 1997 , 2000, Hepatology.

[5]  U. Siebert,et al.  Effectiveness and cost-effectiveness of initial combination therapy with interferon/peginterferon plus ribavirin in patients with chronic hepatitis C in Germany: A health technology assessment commissioned by the German Federal Ministry of Health and Social Security , 2005, International Journal of Technology Assessment in Health Care.

[6]  N. Theise,et al.  Treatment rates in patients with chronic hepatitis C after liver biopsy , 2006, Journal of viral hepatitis.

[7]  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 .

[8]  Man-Fung Yuen,et al.  Viral hepatitis B , 2003, The Lancet.

[9]  Joseph A Hill United States Life Tables , 2013 .

[10]  北村 聖 "The New England Journal of Medicine". , 1962, British medical journal.

[11]  R. Gibbons,et al.  Coronary Revascularization: New Evidence, New Challenges , 2007, Annals of Internal Medicine.

[12]  H. Margolis,et al.  Evaluation of the effectiveness of targeted lookback for HCV infection in the United States—interim results , 2000, Transfusion.

[13]  D. Rein,et al.  Hepatitis C virus antibody positivity and predictors among previously undiagnosed adult primary care outpatients: cross-sectional analysis of a multisite retrospective cohort study. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

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

[15]  D. Fryback,et al.  Toward consistency in cost-utility analyses: using national measures to create condition-specific values. , 1998, Medical care.

[16]  C. Umscheid,et al.  The Treatment Cascade for Chronic Hepatitis C Virus Infection in the United States: A Systematic Review and Meta-Analysis , 2014, PloS one.

[17]  V. Moyer,et al.  Screening for Hepatitis C Virus Infection in Adults: U.S. Preventive Services Task Force Recommendation Statement , 2013, Annals of Internal Medicine.

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

[19]  Michael J. O'Grady,et al.  Economic model of a birth cohort screening program for hepatitis C virus , 2012, Hepatology.

[20]  E. Arias,et al.  United States life tables, 2005. , 2010, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[21]  J. Vertefeuille,et al.  Prevalence of HIV, syphilis, hepatitis B, and hepatitis C among entrants to Maryland correctional facilities , 2004, Journal of Urban Health.

[22]  Z. Jia,et al.  The efficacy and safety of telaprevir-based regimens for treating chronic hepatitis C virus genotype 1 infection: a meta-analysis of randomized trials. , 2013, Internal medicine.

[23]  D. Rein,et al.  Forecasting the morbidity and mortality associated with prevalent cases of pre-cirrhotic chronic hepatitis C in the United States. , 2011, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[24]  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.

[25]  W Marsh,et al.  Long-Term Survival After Liver Transplantation in 4,000 Consecutive Patients at a Single Center , 2000, Annals of surgery.

[26]  W P Havens,et al.  Viral hepatitis. , 1970, The Medical clinics of North America.

[27]  Jennifer A. Roberts,et al.  Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation. , 2006, Health technology assessment.

[28]  J. Tsevat,et al.  Health values of patients with chronic hepatitis C infection. , 2004, Archives of internal medicine.

[29]  T. Welling,et al.  Who Pays for Biliary Complications Following Liver Transplant? A Business Case for Quality Improvement , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[30]  M. Russo,et al.  High Deferral Rates and Poorer Treatment Outcomes for HCV Patients with Psychiatric and Substance Use Comorbidities , 2007, Digestive Diseases and Sciences.

[31]  R. Grant,et al.  Barriers to the treatment of hepatitis C. Patient, provider, and system factors. , 2005, Journal of general internal medicine.

[32]  B. van der Linden,et al.  Hepatitis C screening and treatment outcomes in patients with substance use/dependence disorders. , 2006, Psychosomatics.

[33]  A. McCullough,et al.  Surprisingly Small Effect of Antiviral Treatment in Patients with Hepatitis C , 2002, Annals of Internal Medicine.

[34]  B. Yawn,et al.  Management of Patients With Hepatitis C in a Community Population: Diagnosis, Discussions, and Decisions to Treat , 2004, The Annals of Family Medicine.

[35]  G. Naglie,et al.  Health-State Utilities and Quality of Life in Hepatitis C Patients , 2003, American Journal of Gastroenterology.

[36]  D. Vlahov,et al.  Mortality Risk Among Recent-Onset Injection Drug Users in Five U.S. Cities , 2008, Substance use & misuse.

[37]  R. Cheung,et al.  Effectiveness of a Screening Program for Hepatitis C , 2006, Digestive Diseases and Sciences.

[38]  D. Yankey,et al.  Using Soft Refusal Status in the Cell-Phone Nonresponse Adjustment in the National Immunization Survey , 2012 .

[39]  J. Wong,et al.  Estimating future hepatitis C morbidity, mortality, and costs in the United States. , 2000, American journal of public health.

[40]  R. Groszmann,et al.  American association for the study of liver diseases , 1992 .

[41]  R. Garfein,et al.  Self-Reported Hepatitis C Virus Antibody Status and Risk Behavior in Young Injectors , 2006, Public health reports.

[42]  M. Bilodeau,et al.  Determinants of antiviral treatment initiation in a hepatitis C-infected population benefiting from universal health care coverage. , 2007, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[43]  O. Adeyemi,et al.  Hepatitis C treatment eligibility in an urban population with and without HIV coinfection. , 2004, AIDS patient care and STDs.

[44]  R. Chou,et al.  Screening for Hepatitis C Virus Infection in Adults: A Systematic Review for the U.S. Preventive Services Task Force , 2012, Annals of Internal Medicine.

[45]  Brian L. Pearlman,et al.  svr results of a once-daily regimen of simeprevir (tmc435) plus sofosbuvir (gs-7977) with or without ribavirin in cirrhotic and non-cirrhotic Hcv genotype 1 treatment-naïve and prior null responder patients: The Cosmos study : lb-3 , 2013 .

[46]  Milton C Weinstein,et al.  Empirically calibrated model of hepatitis C virus infection in the United States. , 2002, American journal of epidemiology.

[47]  P. Bedossa,et al.  Natural history of liver fibrosis progression in patients with chronic hepatitis C , 1997, The Lancet.

[48]  Iris R. Mabry-Hernandez,et al.  Screening for hepatitis C virus infection. , 2012, Gastroenterology & hepatology.

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

[50]  D. Thomas,et al.  Natural history of hepatitis C. , 2005, Clinics in liver disease.

[51]  R. Booth,et al.  The association between knowledge of hepatitis C virus status and risk behaviors in injection drug users. , 2002, Addiction.

[52]  E. Schiff,et al.  Cost-effectiveness of screening for chronic hepatitis C infection in the United States. , 2011, Clinical Infectious Diseases.

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

[54]  J. Norcross,et al.  Primary care settings. , 2016 .

[55]  David L. Thomas Hepatitis C Management , 2008 .

[56]  J B Wong,et al.  Estimates of the Cost-Effectiveness of a Single Course of Interferon-2b in Patients with Histologically Mild Chronic Hepatitis C , 1997, Annals of Internal Medicine.

[57]  G. L’italien,et al.  The impact of timing and prioritization on the cost‐effectiveness of birth cohort testing and treatment for hepatitis C virus in the United States , 2013, Hepatology.

[58]  R. Wiesner,et al.  Resource utilization in liver transplantation: effects of patient characteristics and clinical practice. NIDDK Liver Transplantation Database Group. , 1999, JAMA.

[59]  T. S. Jones,et al.  The Costs and Impacts of Testing for Hepatitis C Virus Antibody in Public STD Clinics , 2007, Public health reports.

[60]  Fang Chen Bayesian Modeling Using the MCMC Procedure , 2009 .

[61]  J. Temte Recommended adult immunization schedule-United States, 2013. , 2013, Journal of midwifery & women's health.

[62]  J. Delwaide,et al.  Hepatitis C infection: eligibility for antiviral therapies , 2005, European journal of gastroenterology & hepatology.

[63]  Mark Holodniy,et al.  Cost-Effectiveness Analysis of Risk-Factor Guided and Birth-Cohort Screening for Chronic Hepatitis C Infection in the United States , 2013, PloS one.

[64]  U. S. Centers for Medicare Medicaid Services,et al.  Centers for Medicare & Medicaid Services (CMS) , 2013 .

[65]  H. El‐Serag,et al.  Psychosocial Factors Are the Most Common Contraindications for Antiviral Therapy at Initial Evaluation in Veterans With Chronic Hepatitis C , 2004, Journal of clinical gastroenterology.

[66]  P. Whiting,et al.  A systematic review of the effectiveness and cost-effectiveness of neuroimaging assessments used to visualise the seizure focus in people with refractory epilepsy being considered for surgery. , 2006, Health technology assessment.

[67]  P. Vickerman,et al.  Combination Interventions to Prevent HCV Transmission Among People Who Inject Drugs: Modeling the Impact of Antiviral Treatment, Needle and Syringe Programs, and Opiate Substitution Therapy , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[68]  R. W. Mccollum The natural history of hepatitis. , 1969, Bulletin of the New York Academy of Medicine.

[69]  Harold S Margolis,et al.  Hepatitis C virus genotypes and viral concentrations in participants of a general population survey in the United States. , 2006, Gastroenterology.

[70]  T. McGinn,et al.  Hepatitis C in an Urban Cohort: Who’s Not Being Treated? , 2009, Journal of health care for the poor and underserved.

[71]  M. Alter,et al.  P.445 The knowledge and behaviors of HCV-infected persons identified in a seroprevalence survey, USA, 2001–2002 , 2006 .

[72]  J. Ward,et al.  The Cost-Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary Care Settings , 2012, Annals of Internal Medicine.