Difficulties in Managing Hepatitis C

Tampa—Late last year, the FDA approved oral medications—sofosbuvir and simeprevir—to treat hepatitis C. Both drugs were far superior to previously approved options in terms of safety and efficacy. However, they are both expensive, causing health insurers and other payers to question the high prices.  

During a satellite symposium at the AMCP meeting, speakers discussed the new drugs and the challenges associated with managing hepatitis C, a chronic condition with a growing prevalence throughout the world. The session was supported by an educational grant from AbbVie, Inc.

Jeffrey Dunn, PharmD, senior vice president, VRx Pharmacy Services, LLC, referred to hepatitis C as a “huge clinical burden” and “the silent epidemic” because of its long, indolent course. He cited an article from New England Journal of Medicine [DOI: 10.1056/NEJMp1302973] that indicated only half of the 3.2 million people in the United States with chronic hepatitis C infection had been tested for the disease. Only 220,000 to 360,000 people with chronic hepatitis C were treated for the disease. “We are just seeing the tip of the iceberg [of people diagnosed with hepatitis C],” Dr. Dunn said.

In 2011, the total healthcare costs associated with hepatitis C were approximately $6.5 billion, according to Dr. Dunn. By 2024, the costs are estimated to increase to approximately $9.1 billion. He said the increasing costs are due to more advanced liver diseases, including decompensated cirrhosis, compensated cirrhosis, and hepatocellular carcinoma.

For managed care organizations, hepatitis C creates numerous concerns. Dr. Dunn said there is a need for better ways to identify and treat patients and provide long-term monitoring. He added that the current therapies have limitations, such as adverse events and inconvenient, complex regimens that led to suboptimal adherence. Most of the adverse events are related to pegylated interferon, which contributes to lower compliance and worse outcomes. Hepatitis C is also associated with significant comorbidities, including HIV.

History of Hepatitis C

Paul Kwo, MD, professor of medicine, gastroenterology and hepatology, Indiana University, said hepatitis C was discovered in 1989 and is classified into 6 genotypes. The disease is primarily transmitted through contact with infected blood. Although the disease may not be diagnosed for years or decades after initial infection, 60% to 85% of patients have chronic infection.

From 1990 to 2010, the total deaths related to hepatitis C increased from 45,000 to 70,000, according to Dr. Kwo. Approximately 40% of all liver cancer cases and death from cirrhosis are attributable to hepatitis C, while >30% of people on the waiting list for liver transplants have the disease.

In 2012, the Centers for Disease Control and Prevention (CDC) recommended all adults born between 1945 and 1965 undergo a 1-time test for hepatitis C. The CDC also suggested that anyone with hepatitis C should have a brief alcohol screening/intervention as appropriate and be referred to treatment services. Screening should not replace risk-based testing, according to the recommendations.

Treatment Guidelines and Goals

Dr. Kwo mentioned several medical societies and organizations have published guidelines for diagnosing, managing, and treating hepatitis C, including the American Association for the Study of Liver Diseases, Infectious Diseases Society of America, and American College of Gastroenterology. Among the common elements are that all patients with hepatitis C are potential candidates for antiviral therapy and providers must consider the natural history of the infection and the risks and benefits of antiviral therapy and take steps to minimize liver damage when selecting therapy.

The main goal of therapy, according to Dr. Kwo, is achieving a sustained virologic response (SVR), which he defined as an undetectable hepatitis C ribonucleic acid level using a sensitive assay 24 weeks after completing therapy. Other goals include slowing disease progression, minimizing the risk of hepatocellular carcinoma, improving liver histology, enhancing quality of life, preventing transmission of the virus, and reducing extra-hepatic manifestations.

In 2009, the standard of care included regimens containing pegylated interferon and ribavirin administered for 48 weeks for genotypes 1, 4, 5, and 6 and for 24 weeks for genotypes 2 and 3. SVR rates were around 40% to 50% for genotype 1 and >80% for genotypes 2 and 3.

In 2011, the standard of care changed when the first direct-acting antiviral oral protease inhibitors—boceprevir and telaprevir—were approved. They were used in combination with pegylated interferon and ribavirin and led to higher SVR rates, although they were also associated with toxicities.

With last year’s approval of sofosbuvir and simeprevir, the standard of care changed again. Patients with genotype 1 hepatitis C are recommended to receive triple therapy with sofosbuvir, pegylated interferon, and ribavirin for 12 weeks or 12 weeks of simeprevir plus pegylated interferon and ribavirin for 24 to 48 weeks.

However, Dr. Kwo said “virtually no one” is using the simeprevir combination therapy. He added that the cure rates with the new drugs are >90% and that guidelines indicate boceprevir and telaprevir should no longer be used. “I agree with that [guideline recommendation],” said Dr. Kwo.

By the end of the year, Dr. Kwo predicts there would be an FDA-approved interferon-free regimen. In February, Gilead Sciences, Inc., filed a new drug application for the approval of sofosbuvir plus ledipasvir.

Comparing Hepatitis C Regimens

Before deciding the appropriate hepatitis C drug to use, Dr. Dunn suggested analyzing comparative effectiveness research when possible, but he added that there is a lack of long-term data on the medications. However, he said pharmacy and therapeutics committees have evaluated sofosbuvir and simeprevir based on safety, efficacy, and costs, which are becoming a major issue.

Five years ago, hepatitis C was not among the top 10 disease states with regard to specialty drug spending, according to Dr. Dunn. The disease is now the fifth most expensive category under the pharmacy benefit behind inflammatory conditions, multiple sclerosis, cancer, and HIV.

Dr. Dunn said hepatitis C medications typically are on specialty tiers, have coinsurance, and require prior authorization. With the high costs of the drugs, he recommended that patients should be required to be in case or care management programs to improve adherence. He also said that the cost per SVR is the best way to evaluate reimbursement for the medications. He added that capitated or bundled payments for hepatitis C could encourage doctors to work with pharmacists and nurses to increase compliance.