Cost-Effectiveness of Treatments for Genotype 1 Hepatitis C Virus Infection in Non-VA and VA Populations

Background: Chronic hepatitis C viral (HCV) infection affects millions of Americans. Health care systems face complex choices between highly efficacious, costly treatments. This study assessed the cost-effectiveness of treatments for chronic, genotype 1 HCV monoinfected, treatment-naïve individuals in the Department of Veterans Affairs (VA) and general US health care systems. Methods: The study used a decision-analytic Markov model, employing appropriate payer perspectives and time horizons, and discounting benefits and costs at 3% annually. Interventions included the following: sofosbuvir/ledipasvir (SOF-LDV); ombitasvir/paritaprevir/ritonavir/dasabuvir (3D); sofosbuvir/simeprevir (SOF-SMV); sofosbuvir/pegylated interferon/ribavirin (SOF-RBV-PEG); boceprevir/pegylated interferon/ribavirin (BOC-RBV-PEG); and pegylated interferon/ribavirin (PEG-RBV). Outcomes were sustained virologic response (SVR), advanced liver disease, costs, quality adjusted life years (QALYs), and incremental cost-effectiveness. Results: SOF-LDV and 3D achieve high SVR rates, reducing advanced liver disease (>20% relative to no treatment), and increasing QALYs by >2 years per person. For the non-VA population, at current prices ($5040 per week for SOF-LDV; $4796 per week for 3D), SOF-LDV’s lifetime cost ($293,370) is $18,000 lower than 3D’s because of its shorter duration in subgroups. SOF-LDV costs $17,100 per QALY gained relative to no treatment. 3D costs $208,000 per QALY gained relative to SOF-LDV. Both dominate other treatments and are even more cost-effective for the VA, though VA aggregate treatment costs still exceed $4 billion at SOF-LDV prices of $3308 per week. Drug prices strongly determine relative cost-effectiveness for SOF-LDV and 3D; with price reductions of 20% to 30% depending on health system, 3D could be cost-effective relative to SOF-LDV. We currently lack head-to-head regimen effectiveness trials. Conclusions: New HCV treatments are cost-effective in multiple health care systems if trial-estimated efficacy is achieved in practice, though, at current prices, total expenditures could present substantial challenges.

[1]  Jeremy D. Goldhaber-Fiebert,et al.  Assessment of Alternative Treatment Strategies for Chronic Genotype 1 Hepatitis C , 2013 .

[2]  A. V. D. Meer Faculty Opinions recommendation of Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. , 2016 .

[3]  E. Armstrong,et al.  Burden of illness of hepatitis C from a managed care organization perspective , 2004, Current medical research and opinion.

[4]  M. Weinstein,et al.  The Cost-Effectiveness of Sofosbuvir-Based Regimens for Treatment of Hepatitis C Virus Genotype 2 or 3 Infection , 2015, Annals of Internal Medicine.

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

[6]  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 .

[7]  R. Goetzel,et al.  Cost Burden of Illness for Hepatitis C Patients with Employer-Sponsored Health Insurance , 2002 .

[8]  J. Ward,et al.  The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus. , 2015, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  P. Hayes,et al.  Excess liver‐related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care , 2011, Hepatology.

[10]  C. McAdam-Marx,et al.  All-Cause and Incremental Per Patient Per Year Cost Associated with Chronic Hepatitis C Virus and Associated Liver Complications in the United States: A Managed Care Perspective , 2011, Journal of managed care pharmacy : JMCP.

[11]  D. Rein,et al.  The burden of hepatitis C to the United States Medicare system in 2009: Descriptive and economic characteristics , 2016, Hepatology.

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

[13]  T. Wagner,et al.  Using Average Cost Methods to Estimate Encounter-Level Costs for Medical-Surgical Stays in the VA , 2003, Medical care research and review : MCRR.

[14]  D. Russell,et al.  Quality-of-Life Weights for the US Population: Self-Reported Health Status and Priority Health Conditions, by Demographic Characteristics , 2007, Medical care.

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

[16]  P. Belperio,et al.  A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[17]  Kenneth J. Smith,et al.  Cost‐effectiveness of new antiviral regimens for treatment‐naïve U.S. veterans with hepatitis C , 2016, Hepatology.

[18]  S. Saab,et al.  Cost‐effectiveness of Ombitasvir/Paritaprevir/Ritonavir, Dasabuvir+Ribavirin for US Post‐Liver Transplant Recurrent Genotype 1 HCV , 2016, Liver international : official journal of the International Association for the Study of the Liver.

[19]  D. Mitra,et al.  Treatment patterns and adherence among patients with chronic hepatitis C virus in a US managed care population. , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[20]  E. Monnet,et al.  Long‐term outcome of chronic hepatitis C in a population‐based cohort and impact of antiviral therapy: a propensity‐adjusted analysis , 2011, Journal of viral hepatitis.

[21]  P. Belperio,et al.  Impact of race/ethnicity and gender on HCV screening and prevalence among U.S. veterans in Department of Veterans Affairs Care. , 2014, American journal of public health.

[22]  M. Holodniy,et al.  Sofosbuvir-Based Treatment Regimens for Chronic, Genotype 1 Hepatitis C Virus Infection in U.S. Incarcerated Populations , 2014, Annals of Internal Medicine.

[23]  Wei Yu,et al.  Estimating the Costs of VA Ambulatory Care , 2003, Medical care research and review : MCRR.

[24]  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.

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

[26]  A. Lok,et al.  Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. , 2014, The New England journal of medicine.

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

[28]  G. Dore,et al.  Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United States , 2015, Annals of Internal Medicine.

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

[30]  T. O'Brien,et al.  No scientific basis to restrict 8 weeks of treatment with ledipasvir/sofosbuvir to patients with hepatitis C virus RNA <6,000,000 IU/mL , 2016, Hepatology.

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

[32]  Jagpreet Chhatwal,et al.  Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment With Sofosbuvir and Ledipasvir in the United States , 2015, Annals of Internal Medicine.

[33]  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.

[34]  D. Owens,et al.  New Protease Inhibitors for the Treatment of Chronic Hepatitis C , 2012, Annals of Internal Medicine.

[35]  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.

[36]  J. Tice,et al.  Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population. , 2016, JAMA internal medicine.

[37]  E. Bini,et al.  Can We Predict the Degree of Fibrosis in Chronic Hepatitis C Patients Using Routine Blood Tests in Our Daily Practice? , 2008, Journal of clinical gastroenterology.

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

[39]  Oliver Lenz,et al.  Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial , 2014, The Lancet.

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

[41]  J. Mccombs,et al.  Economic burden associated with patients diagnosed with hepatitis C. , 2011, Clinical Therapeutics.

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

[43]  M. Gold,et al.  Panel on cost-effectiveness in health and medicine. , 1996, Medical care.

[44]  William M. Lee,et al.  Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. , 2009, The New England journal of medicine.

[45]  William M. Lee,et al.  Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. , 2010, Gastroenterology.