Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

By Harinder S. Chahal, PharmD, MSc; Elliot A. Marseille, PhD; Jeffrey A. Tice, MD; Steve D. Pearson, MD, MSc; Daniel A. Ollendorf, PhD; Rena K. Fox, MD; James G. Kahn, MD, MPH
JAMA Internal Medicine, November 23, 2015 (online first)

In the United States, prevalence of chronic hepatitis C virus (HCV) infection is estimated to be 3.2 million and is the leading cause of liver-related deaths, hepatocellular carcinoma, and liver transplant.

With the introduction of HCV nucleotide analogue nonstructural protein 5A and B inhibitors, such as ledipasvir, ombitasvir, dasabuvir, and sofosbuvir, treatment duration has decreased for most patients to 12 weeks or less, with reduced toxic effects by the exclusion of interferon and often with the exclusion of ribavirin. The cure rate with the new therapies generally exceeds 90% and reaches 100% in some subgroups in clinical trials. The new drugs cost $1000 per day or more based on the wholesale acquisition price. Such costs are prohibitive for many patients and health care systems.

From the Discussion

The new HCV interferon-free therapies offer potentially huge individual and societal benefits but at a large cost. Health plans and health systems concerned about costs frequently require evidence of advanced liver fibrosis before authorizing the new therapies. We herein examined the health impact, cost, and cost-effectiveness of earlier treatment.

Although early treatment with sofosbuvir-ledipasvir is expensive, the net cost is substantially lower owing to savings in medical care and the likelihood of later treatment with a delayed treatment policy. Furthermore, we found substantial short- and long-term health gains. Thus, for sofosbuvir-ledipasvir treatment, treating patients at all fibrosis stages compared with waiting for advanced fibrosis is cost-effective (<$50 000 per QALY [quality-adjusted life-years] gained). A detailed analysis of timing of therapy by fibrosis stage shows that treating the disease at as early as stage F1 is cost-effective (ICERs [incremental cost-effectiveness ratios] of $50 000-$150 000 per QALY gained) and less than $50 000 per QALY gained when treatment is initiated at stage F2 vs stage F3. The ICER is lower when treatment is initiated at stage F3 compared with waiting for cirrhosis (stage F4).

Although the new therapies promise a high SVR [sustained virologic response], their long-term effects on clinical outcomes are not yet known. Sustained virologic response, a surrogate marker, may not lead to better long-term health outcomes with new treatments. Past studies with older regimens, however, have shown that achieving SVR can result in positive, long-term clinical benefits for patients. A 2011 systematic review61 found that achieving SVR can reduce liver-related mortality, incidence of hepatocellular carcinoma, and decompensation and foster regression of fibrosis and cirrhosis.

For budgetary considerations, if only 50% of eligible patients with HCV genotype 1 were to be treated with sofosbuvir-ledipasvir during the next 5 years, the cost of drugs in the United States would be $53 billion at current prices. Many payers negotiate prices, as has been seen with exclusivity deals with drug manufacturers. If a mean 46% reduction in drug prices occurred, the cost of treating 50% of patients with HCV genotype 1 during the next 5 years could be as high as $29 billion, partly offset by $3 billion in savings in the management of chronic HCV and advanced liver disease.


This analysis suggests that treatment with new HCV drugs is cost-effective when started with any evidence of fibrosis (stage F1). Because of the investment required for these drugs, budgetary constraints on health systems typically restrict access to insured patients until they experience higher levels of liver damage or failure of older treatments, and uninsured patients would be unable to receive treatment without patient assistance programs. A reduction in the price will improve cost-effectiveness and increase affordability and access.


Treatment of Hepatitis C Virus Infection in Real Life

By Hal F. Yee Jr, MD, PhD
JAMA Internal Medicine, Invited Commentary, November 23, 2015 (online first)

The US Food and Drug Administration approved the first daily oral antiviral for the treatment of hepatitis C virus (HCV) infection in November 2013. This and subsequent antivirals represented a marked improvement compared with the prior regimen of ribavirin and injectable interferon. However, the extraordinary costs of the medications have resulted in controversy as to which patients can and should be offered therapy.

In their joint HCV treatment recommendations, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America (AASLD-IDSA) have recommended treatment “for all patients with chronic HCV infection, except those with limited life expectancy due to nonhepatic causes.”

The AASLD-IDSA panel tacitly acknowledges one of these obstacles in its recommendation that, “if resources limit the ability to treat all infected patients immediately as recommended, then it is most appropriate to treat those at greatest risk of disease complications before treating those with less advanced disease.” How might we reconcile the recommendation to treat all patients with HCV with the real-world constraints facing our patients, physicians, and health care systems?

The most prominent practical challenge faced in treating everyone infected with HCV is, as Chahal and colleagues write, the aggregate costs of the new antivirals. The retail cost of the antivirals for a single course of the most common treatment regimen approaches $100 000. In 2014, the first full year after approval of the initial oral antiviral treatment for HCV, total spending on medications for the treatment of HCV exceeded $12 billion. This amount represented more than 3% of the nation’s total prescription drug expenditures. Moreover, 70% of the increase in spending on prescription drugs during the initial year (ie, 2014) of Medicare expansion related to the Affordable Care Act was owing to spending on anti-HCV agents. Given an estimated 3 million US patients with HCV, funding to treat every infected person immediately appears problematic. Hence, those at the greatest and most urgent risk for clinical complications of their infection should be treated first as recommended by the AASLD-IDSA panel.

Less noticed than medication costs, but equally important to patients with HCV, is the difficulty of gaining access to a physician who can initiate treatment promptly. Many explanations for this difficulty exist. Notably, patients with liver diseases, including HCV, are represented disproportionally in populations with health disparity that have poorer access to clinical care, especially high-cost specialty care. In addition, these populations have cultural, environmental, and social determinants that negatively affect their health outcomes. Such patients face challenges such as being uninsured or underinsured, residing in locations far from specialty care or lacking transportation, not speaking or reading English, or lacking the ability to navigate a complex health care environment. Approaches for treating HCV that are equitable, so that every patient has fair access to treatment, and efficient, so that as many patients as possible can be offered therapy with the resources that are available, must be established.

Robust debate continues about which individuals to treat for HCV. Targeting those individuals at the greatest and most urgent risk for complications of HCV makes sense but only accomplishes a kind of triage. Policy and market initiatives to reduce the cost of HCV medications would enable treatment of many more people. Finally, individuals with HCV are overrepresented in health-disparity populations, and we must put in place mechanisms to reduce barriers to equitable care.


Expensive Drugs That Cure Hepatitis C Are Worth The Cost, Even At Early Stages Of Liver Fibrosis

By Laura Kurtzman
UCSF, November 23, 2015

It is worthwhile to give patients expensive new drugs that can cure their hepatitis C much earlier than some insurers are now willing to pay for them, according to a UC San Francisco study that models the effects of treating the disease early versus late in its development.

Researchers said they were surprised by the findings, since the drugs can cost up to $100,000 for a full course of treatment. But when they factored in the long-term medical cost of delaying treatment for hepatitis C, they found the savings, in combination with improvements in the quality of patients’ lives, were enough under current standards to justify using them even at early stages of liver fibrosis. Researchers said the drugs were therefore cost effective.

“The budgetary implications of widespread treatment are quite large at current drug prices,” said James G. Kahn, MD, MPH, a professor in the UCSF department of epidemiology and biostatics, as well as medicine. “However, these costs are time-limited, and they are lower than some other treatments that are less effective. In the U.S., we spend more than $140 billion a year treating cancer, often with less health benefit than is provided by the new hepatitis C treatments.”

The researchers said it was important to broaden the discussion beyond cost-effectiveness, to include the price of drugs.

“The benefits of early therapy are significant, since it increases the number of healthy life years for patients and decreases their chances of getting serious liver diseases, like liver failure and liver cancer,” said Harinder Chahal, PharmD, MSc, an assistant adjunct professor in the UCSF department of clinical pharmacy. “But the current prices are keeping early treatment out of reach for many patients, and this needs to be addressed.”

This important study shows that the new hepatitis C drugs, such as Harvoni, are cost effective for early disease as well as late disease. The problem is that about 3.2 million people have hepatitis C infections, and, at a per-patient cost of close to $100,000, the implications are huge for public and private health care budgets.

Not only is money an issue, but the populations disproportionately affected have health disparities with poorer access to clinical care, and are often uninsured or underinsured. As Hal Yee states in his commentary, “Approaches for treating HCV that are equitable, so that every patient has fair access to treatment, and efficient, so that as many patients as possible can be offered therapy with the resources that are available, must be established.”

One of the more important measures that we could adopt to address this disparity would be a single payer national health program. Not only would everyone be fully covered, but also a well designed single payer system improves resource allocation, thereby improving access.

As far as the high prices paid for these new drugs, a single payer system would use administered pricing to obtain the best value, much as we already do with our Medicaid and VA drug programs.

Also, once the people of our nation have accepted the reality that public funding and public administration of our health care financing system create much greater value for us, they may also accept the principle that our government should play a greater role in guiding pharmaceutical research and development in the direction of providing us with even greater value for our drugs and biologics while directing the industry away from drug development policies designed primarily to further enrich the billionaires.

Oh, and generously fund the needle exchange programs since that is now the primary source of hepatitis C transmission. You can fund an awful lot of needles and syringes with the $100,000 that it costs to treat just one hepatitis C patient.