Researchers from The University of Texas MD Anderson Cancer Center in Houston reported at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) their attempt to estimate the cost of treating all patients in the United States with hepatitis C virus (HCV) compared with the potential cost savings. Hepatitis C, a liver disease that results from infection with the Hepatitis C virus, can cause serious health problems including liver damage, cirrhosis, and even death, and is a leading cause of liver cancer and the leading reason for liver transplants. The disease is insidious, and infected persons often have no symptoms and live for decades without feeling sick. In approximately 75%–85% of persons, HCV persists as a chronic infection, placing infected persons at risk for liver cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic complications that develop over the decades following onset of infection.

The CDC points to new direct-acting antiviral medicines now available, that when added to the standard treatment can increase the effectiveness and shorten treatment time for many people. For many people with Hepatitis C, medical treatment can result in the virus no longer being detected in the blood. This is referred to as a sustained viral response or SVR. However, treatment with the new medications is expensive.

The AASLD notes that while the newest and most effective drugs for treatment of hepatitis C have a cure rate of up to 98 percent, the cost of these therapies has been controversial and that accurately assessing the cost of treating all patients with HCV in the US has yet to be determined.

They point out that part of the problem is getting an accurate count of the number of Americans with HCV, since the disease is often asymptomatic and many are undiagnosed. The Centers for Disease Control and Prevention (CDC) recommends a one-time age-based screening for HCV infection for all Americans born from 1945 to 1965 (ie: baby boomers), noting that HCV is an increasing cause of morbidity and mortality in the United States, with many of the estimated 2.7–3.9 million persons living with HCV infection unaware they are infected and not receiving care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945–1965 comprise an estimated 27% of the population, they account for approximately three-quarters of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. The agency projects that one-time testing of everyone born during 1945 through 1965 would find an estimated 800,000 undiagnosed Hepatitis C cases. Risk-based screening was the standard protocol before the CDC’s recent recommendation.

For their study, the MD Anderson research team developed a model that simulated the natural history of HCV in treatment-naive and treatment-experienced patients and included currently diagnosed patients, as well as those who would be diagnosed by the age-based screening recommended by the CDC. They then simulated treatments using the newly approved direct-acting antiviral therapies based on a Practice Guidance for treating patients with HCV issued by the AASLD and the Infectious Diseases Society of America in January 2014, and further included recently approved ledipasvir-based therapies in their investigations. They also used published sources for specific annual and treatment costs.

The total number of patients to be treated in their model was 1.6 million, and they concluded that treatment cost to all payers would be in a range of $136 – 188 billion over the next five years. That cost is $65 billion more than the cost of drugs used prior to the new direct-acting antivirals. Cost-offsets because of the new therapies would be only $16 billion dollars. Because of this, the researchers concluded that treating the large number of HCV patients would be “immense and likely unsustainable.”

According to Dr. Jagpreet Chhatwal, PhD, an Assistant Professor in the Department of Health Services Research, Division of Cancer Prevention and Population Sciences at the MD Anderson Center and principal investigator for the study, “The best strategy is to treat everyone. Unfortunately, we are not seeing it happening in practice because of the cost of treatment. Either we need to reduce the price of drugs, or make the best use of available resources by evidence-based prioritization.”

The researchers conclude by calling for price reductions for the new drugs, additional resources to treat HCV, and value-based patient prioritization. In summary, Dr. Chhatwal observes in a AASLD release that “We need a multiple-pronged approach consisting of additional government funding, price negotiations, and need-based prioritization to effectively treat all HCV patients in the US.”

A study published in Hepatology, the official journal of the American Association for the Study of Liver Diseases, entitled “Projected Health and Economic Impact of Hepatitis C on the United States Medicare System From 2010 to 2024” (First published: 1 October 2014 DOI: 10.1002/hep.27460), coauthored by David B. Rein, John S. Wittenborn, Danielle Liffmann, and Joshua M. Borton, estimates that over a million Americans with hepatitis C virus (HCV) will age into Medicare by 2024, but information on the clinical and economic burden of HCV in Medicare is limited.

The researchers used primary data to estimate the clinical burden of HCV in Medicare in 2009 and forecast this burden until 2024 assuming three treatment strategies. The Medicare administrative claims data referenced contained 122,417 patient years of diagnosed HCV across the years 2002-2009. Using ICD-9-CM codes, they divided HCV patients into six stages; chronic HCV, cirrhosis, decompen-sated cirrhosis (DCC), hepatocellular carcinoma, transplant/ post-transplant, and death occurring in a year with diagnosed HCV. They then estimated incremental annual costs of each stage using a two-part health expenditure. Weighting the data to estimate the Medicare population in each HCV stage as of 2009 and estimated new cases of HCV entering Medicare from 2010-2024 using NHANES, there researchers used a simulation to forecast future HCV health outcomes in Medicare, assuming no treatment (NT), treatment with pegylated interferon, ribavirin, and a protease inhibitor (PRPI), and an all-oral high efficacy regimen (AO). They estimated 796,232 patients with HCV in Medicare in 2009, of whom 63.1% had chronic infection only, 9.9% had cirrhosis, 14.7% had DCC, 2.5% had HCC, 2.6% transplant or post-transplant maintenance, and 7.2% died during 2009, and project that between 2010 and 2024, an additional 1,027,066 individuals with chronic HCV would enter the Medicare system. Of the cumulative 1,823,298 individuals with chronic HCV currently in or entering Medicare from 2010-2024, with NT we forecast that 661,060 (36.2%) would die from HCV or other causes while in a diagnosed state of DCC, HCC, or transplant/post-transplant.

However, they note that treatment with PRPI reduced deaths states providing it by 29,720, and increased undiscounted QALYs (quality-adjusted life-year — a measure of disease burden, including both the quality and the quantity of life lived) by 1,562,119. Treatment with AO reduced deaths in these states by 126,163 and increased undiscounted QALYs by 7,692,906.

The researchers observe that incremental costs of non-antiviral HCV treatment were higher in chronic HCV and cirrhosis than values used in prior cost-effectiveness models while costs for advanced stages were similar. Medicare contained more diagnoses for advanced disease in 2009 Medicare population than predicted by previous simulation. Treatment, especially treatment with interferon free, all oral regimens could substantially reduce morbidity and mortality from HCV within Medicare. Because of the large proportion of Medicare patients that enter the program in advanced stages of disease, they conclude that treatment prior to Medicare entry is likely to be more effective in mitigating the health consequences of HCV.

Other research has noted that Sofosbuvir + pegIFN/RBV yields more favorable future health and economic outcomes than current treatment regimens for patients across all levels of treatment experience and cirrhosis stage, as well as for individuals with or without HIV co-infection.

An article in American Journal of Managed Care entitled HCV Care: Access and Cost of Treatment reports that at The Liver Meeting 2014, an annual meeting organized by the American Association for the Study of Liver Disease, held this year in Boston, Massachusetts, November 7 to 11, MD Anderson’s Dr. Chhatwal told the audience during his talk, “The Economic Impact of Sofosbuvir- and Simeprevir-based HCV Treatment in the United States,” that although sofosbuvir (SOF)-, simeprevir (SMV)-, and ledipasvir (LDV)-based therapies for chronic hepatitis C virus (HCV) infection offer highly efficacious, safer but substantially more expensive options than the old standard-of-care (oSOC), the economic impact of the uptake of these new treatments and resulting downstream cost savings remain unknown

Dr. Zobair Younossi, MD, MPH, Chairman, Inova Fairfax Hospital, and vice president for research of Inova Health System, and also a Professor of Medicine at Virginia Commonwealth University, Inova Campus and Affiliate Professor of Biomedical Sciences at George Mason University, presented something of a counter-argument to Dr. Chhatwal’s data, based on research from his group evaluating the economic impact of oral regimens for HCV coupled with the recent CDC-recommended birth cohort screening.

The objective of the Younossi group’s study was to determine potential cost-effectiveness and population impact of different strategies to screen for HCV and treat it with the most effective all-oral regimens. The researchers used a Markov modeling approach to estimate the cost-effectiveness of screening and treating patients with HCV have created a model based on five strategies of treatment and simulated patients until death:
• Risk-based screening and treating all patients with HCV
• Age-based screening and treating all patients with HCV
• Risk-based screening and treating patients based on liver disease stage
• Age-based screening and treating patients based on liver disease stage
• No screening and no treatment

They assumed treatment for fibrosis stages F2 to F4, a 98 percent cure rate, and the cost of the drugs at current prices, and that 1.2-1.4 million new patients would be diagnosed with HCV from age-based screening. Treatment effectiveness was measured in quality-adjusted life years, which assumes that patients with HCV would live their lives without HCV progressing to cirrhosis, decompensated liver disease, or liver transplantation. Different screening and treatment strategies were compared to each other based on the standard threshold for cost-effectiveness (incremental cost-effectiveness ratio or ICER) from a societal perspective.

The authors found that birth cohort screening followed by treating all HCV (+) patients was the most cost-effective strategy with ICERs well below the accepted threshold of $50,000 per quality adjusted years of life gained. Lead investigator Dr. Younossi concludes that “screening and treating baby boomers with highly effective and well tolerated all oral anti-HCV regimens are highly cost-effective with great health and economic benefits at the population level.”

Treatment based on staging, he says in a AASLD release, implied treatment for fibrosis stages F2-F4 with subsequent staging every 5 years for F0-F2. Treatment in BCS was phased-in over 5 years from the initiation of the screening program. Oral therapy was assumed to have 98% SVR at a cost of $1000/day for 12 weeks, with no discontinuation of treatment. Drug costs were based on the cost of acquisition. Effectiveness was measured in quality-adjusted life years (QALYs) and disease progression.

The study, published in the journal Alimentary Pharmacology & Therapeutics entitled “Cost-effectiveness Analysis of Sofosbuvir Plus Peginterferon/ribavirin in the Treatment of Chronic Hepatitis C Virus Genotype 1 Infection” (Aliment Pharmacol Ther 2014; 40: 657–675 doi:10.1111/apt.12871) coauthored by S. Saab of the Department of Medicine at the University of California, Los Angeles, California; S. C. Gordon of the Henry Ford Health System Gastroenterology K-7 unit at Detroit, Michigan; H. Park of the University of Florida, Gainesville; M. Sulkowski of the School of Medicine, Johns Hopkins University, Baltimore, Maryland; A. Ahmed of the Stanford University Medical Center at Stanford, California; and Z. Younossi of Inova Health Systems, Fairfax, Virginia, notes that Sofosbuvir, an oral NS5B nucleotide polymerase inhibitor, is indicated for the treatment of patients infected HCV, and evaluates long-term health economic outcomes of sofosbuvir + pegylated interferon alfa/ribavirin (pegIFN/RBV) compared with current treatments in U.S. patients infected with HCV genotype 1.

Using the aforementioned decision-analytic Markov model developed to estimate health outcomes, number needed to treat and short-term and long-term economic outcomes, including incremental cost-effectiveness ratios and cost per sustained virological response (SVR), the researchers evaluated several sofosbuvircomparator regimen pairings for a cohort of 10,000 patients divided into three cohorts: treatment-naive, treatment-experienced, and treatment-naive human immunodeficiency virus (HIV) co-infected. Subgroup analyses were conducted for treatment-nave patients with and without cirrhosis.

They conclude that Sofosbuvir + pegIFN/RBV was typically associated with the lowest 1-year cost per SVR, noting that when considering the lifetime incremental cost per quality-adjusted life-year gained, sofosbuvir + pegIFN/RBV was the most cost-effective treatment option assessed. Sofosbuvir + pegIFN/RBV generally dominated (less costly and more effective than) boceprevir + pegIFN/RBV, telaprevir + pegIFN/RBV and simeprevir + pegIFN/RBV.

The researchers conclude that Sofosbuvir + pegIFN/RBV yields more favorable future health and economic outcomes than current treatment regimens for patients across all levels of treatment experience and cirrhosis stage, as well as for individuals with or without HIV co-infection. They observe that incremental costs of non-antiviral HCV treatment were higher in chronic HCV and cirrhosis than values used in prior cost-effectiveness models while costs for advanced stages were similar. Medicare contained more diagnoses for advanced disease in 2009 Medicare population than predicted by previous simulation. Treatment, especially treatment with interferon free, all oral regimens could substantially reduce morbidity and mortality from HCV within Medicare.

The authors found that birth cohort screening followed by treating all HCV (+) patients was the most cost-effective strategy with ICERs well below the accepted threshold of $50,000 per quality adjusted years of life gained. The, concluded that “screening and treating baby boomers with highly effective and well tolerated all oral anti-HCV regimens are highly cost-effective with great health and economic benefits at the population level.”

Because of the large proportion of Medicare patients that enter the program in advanced stages of disease, lead investigator Dr. Younossi concludes that the availability of highly efficacious and well tolerated all-oral regimens for CHC patients with excellent tolerability makes BCS of the baby boomers highly cost-effective with great health and economic benefits at the population level.

Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965 can be found at
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6104a1.htm.

For more information, visit:
http://bit.ly/1zhzLWe

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD’s vision is to prevent and cure liver diseases. This year’s Liver Meeting, held in Boston, November 7-11, brought together more than 9,000 researchers from 55 countries.

For more information, visit:
http://www.aasld.org

Sources:
American Association for the Study of Liver Diseases (AASLD)
The Centers for Disease Control and Prevention (CDC)
Alimentary Pharmacology & Therapeutics
Hepatology
University of Texas MD Anderson Cancer Center
Infectious Diseases Society of America
American Journal of Managed Care

Image Credits:
University of Texas MD Anderson Cancer Center
Inova Fairfax Hospital