Pricey HCV Drugs Worth the Cost

Treating all patients with hepatitis C (HVC) genotype 1, fibrosis stages 0-4, with the expensive new drugs would be cost-effective compared with waiting until patients progress to stages F3 or F4, thanks to reductions in advanced disease complications and quality-of-life improvements, researchers reported.

Based on calculations from a patient simulation model, initiating treatment as early as possible, compared with stages F3 or F4, was cost-effective with 0.73 quality-adjusted life-years (QALYs) gained, and $28,899 per year, with an incremental cost-effectiveness ratio (ICER) of $39,475 per QALY gained, James G. Kahn, MD, MPH, of the University of California San Francisco, and colleagues, reported in JAMA Internal Medicine.

However, an early treatment strategy would also increase the aggregate costs, the researchers noted.

“Given an estimated 3 million U.S. patients with HCV, funding to treat every infected person immediately appears problematic,” Hal F. Yee Jr, MD, PhD, of the Los Angeles County Department of Health Services, wrote in an accompanying editorial. “Targeting those individuals at the greatest and most urgent risk for complications of HCV makes sense but only accomplishes a kind of triage.”

According to Yee, the American Association for the Study of Liver Diseases and the Infectious Disease Society of America (AASLD-IDSA) both recommend HCV treatment for patients at all stages of the disease, however those with the most severe stages, except those with limited life expectancy due to nonliver related conditions, should receive treatment first.

But with total spending on oral antiviral HCV treatment reaching $12 billion in 2014, as individual courses of treatment run close to $100,000, Yee suggested that policy and market initiatives to reduce the cost of medication would allow for widening the treatment population. “We must ensure also that as many individuals with HCV as possible are treated with available resources by driving efficiencies through innovation.”

“There is a current shortage of health professionals who are equipped to deal with the nuances of fibrosis staging, surveillance for disease-related complications (e.g., portal hypertension and hepatocellular carcinoma), and potential metabolic interactions between antiviral drugs and other prescription and nonprescription medications,” Steven D. Lidofsky, MD, PhD, of the University of Vermont College of Medicine. “Consequently, factors that exacerbate inequities in access to HVC treatment are likely to be amplified in economically disadvantaged areas and rural regions.”

“Overall, I think that the manuscript is well written and the model that they developed was comprehensive and reasonable in an effort to determine cost-effectiveness of current direct-acting antiviral therapies in a disease that disproportionately impacts adults and baby boomers in our society and has been under the radar screen of the general public, Congress, etc. for decades with an overall prevalence four times that of HIV infection,” Robert John Fontana, MD, of the University of Michigan, said in an email to MedPage Today.

“The high price of each treatment course [per] patient has a lot of impact to patients, insurers, and society,” he added.

To analyze the implications of treatment at various stages of liver fibrosis, Kahn’s team created a simulation model comparing treatment cost for all treatment-naive patients with treatment for patients with advanced fibrosis. The model categorized treatment for each stage of fibrosis through the 5 METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) liver fibrosis stages from no fibrosis (F0), portal fibrosis without septa (F1), portal fibrosis with rare septa (F2), numerous septa without cirrhosis (F3), and cirrhosis (F4).

Drug costs were based on 2015 wholesale acquisition price for 8 or 12 weeks of sofosbuvir-ledipasvir combo therapy.

The model assumed a single patient profile, and made projections for 1,000 patients based off data collected in 2014. Treatment duration were assigned based on baseline viral loads. Patients with less than 6 million IU/mL and no cirrhosis were assigned 8 weeks of treatment, and all the rest, as well as all F4 patients were assigned to 12 weeks. The patients were assumed to have been born in 1955 (age 60 at time to analysis), 75 kg, and aware of their HVC infection.

Kahn’s team found that the earlier patients were treated, the more cost-effective treatment became. Initiating treatment during stage F1 fibrosis was associated with $81,165 QALY gained compared with waiting until the patient progressed to F2, which added an extra $19,833 per QALY gained, compared with waiting until stage F3.

However, the earliest possible initiation of treatment, at stage F0, would result in $187,065 per QALY gained compared with waiting until the patient reached F1.

Kahn’s group did a 5-year estimate, and projected that treating 50% of all eligible HCV genotype 1 patients in the U.S. would cost $53 billion, though if the drug costs were reduced by 46%, that total treatment cost would drop to $29 billion. The cost of treating only F3 and F4 patients in this same model would run $30 billion for, which could drop to $16 billion if drug costs were reduced by 46%.

Kahn and colleagues argued that the $29 billion price tag could partially be offset by $3 billion in savings in the management of chronic HCV and advanced liver disease.

The researchers proposed that initiating treatment in the early stages of the disease would likely prevent advanced disease complications at risk for occurring in stages F3 and F4. The simulation model estimated that early treatment would avert 26% of liver transplant cases, 17% of decompensated cirrhosis cases, 27% of hepatocellular carcinoma, and 25% of deaths due to liver complications.

Kahn’s group reported several study limitations, including murky calculations around the impact of sustained virologic response (SVR) on disease progression and associated healthcare costs, and no calculations for how reducing the rates of HCV transmission could effect overall healthcare costs. Also, the simulation model used a single patient for the disease course model, and other model variables such adverse events and costs would likely not represent full treatment coverage in practice, they wrote.

“[T]he vast majority of payers currently restrict access to these medications to those with advanced liver disease, typically F3 and F4,” Joseph K. Lim, MD, of Yale Liver Center, said in an email to MedPage Today. “Patients with F0-F2 fibrosis are given the message that they must become sicker before they can undergo treatment when disease progression itself can be prevented.”

“Further evolution in drug pricing and discounting will likely be necessary to create meaningful expansion of drug access to patients with hepatitis C in the U.S.,” Lim said.

“This study has implications for third party payers, especially Medicaid programs which put restrictions on treatment of HCV on some of the most vulnerable patients,” Mamta Jain, MD, of UT Southwestern Medical Center in Dallas, said in an email to MedPage Today. “HVC treatment is costly, but this cost has to be balanced with the cost savings that is realized by reducing the number of complications of advanced liver disease. Treating hepatitis C at any stage of liver disease is cost-effective.”