Hepatitis C Therapy Options Expanding

Las Vegas—Throughout the world, 200 million people have been infected with the hepatitis C virus, including 4.1 million in the United States. Until recently, though, patients had few treatment options. In May, the US Food and Drug Administration (FDA) approved 2 drugs (telaprevir and broceprevir) to be used in combination with peginterferon and ribavirin to treat patients with genotype 1 hepatitis C. The new therapies have led to increased response rates. The standard of care for patients with genotype 2 and 3 disease remains a combination of peginterferon and ribavirin. Neither telaprevir nor broceprevir is approved for genotype 2 or 3, and the drugs cannot be used alone. In addition, there are approximately 50 hepatitis C drugs in development that are examining different targets, according to David Winston, MD, FACP, section head of gastroenterology and hepatology at CIGNA Healthcare of Arizona. Dr. Winston spoke at the Fall Managed Care Forum in a session titled Update in the Guidelines and Treatment of Hepatitis C. The approvals earlier this year and the large pipeline have brought attention to hepatitis C, which, unlike HIV or hepatitis B, can be cured with appropriate therapy. There are 6 genotypes of hepatitis C, which is a single-stranded RNA virus. Among patients in the United States, 74% have genotype 1, 22% have genotype 2, and 4% have genotype 4, 5, or 6, according to 2 studies that Dr. Winston discussed. Chronic hepatitis C is found in an estimated 170 million people worldwide and 3.2 million Americans, although Dr. Winston said the numbers are likely higher because the government does not track the prison population, the homeless, and other subsets of people. Of the 3.2 million Americans with hepatitis C, 75% are undiagnosed. Of the remaining people diagnosed with hepatitis C, 59% do not receive treatment. Dr. Winston said there is a high prevalence of undiagnosed and untreated patients with hepatitis C because they typically are asymptomatic, unaware of their infection, or unaware of the risks associated with the disease. The most common symptom related to hepatitis C is fatigue (occurring in 80% of patients), but Dr. Winston said fatigue “is not a particularly useful symptom” because many people are fatigued, not just those with hepatitis C. If a primary care provider does not diagnose the presence of hepatitis C early and begin treatment, patients may develop cirrhosis, which can decrease survival and quality of life and increase the economic burden. Dr. Winston said the peak prevalence of hepatitis C occurred in 2001, but complications related to the disease are still growing, with the prevalence of cirrhosis expected to peak between 2010 and 2030 and the prevalence of hepatocellular carcinoma anticipated to peak in 2019. Approximately two-thirds of hepatitis C cases are infected through using intravenous drugs, while other risk factors include receiving blood, blood products, or a solid organ transplant before 1992, using intranasal cocaine with shared implements, or getting a body piercing or tattoo with contaminated needles. He added that several factors contribute to the progression of hepatitis C, including alcohol consumption (>30 g/day in males and >20 g/day in females), disease acquisition after 40 years of age, obesity, HIV or hepatitis B coinfection, hepatic steatosis, and daily cannabis use. Other factors such as transaminase level, viral load, mode of transmission, and genotype do not influence progression. The virus is most common in men, in African Americans, and in people between 35 and 54 years of age. According to Dr. Winston, primary care physicians must assess and screen any patient with risk factors for hepatitis C, including patients with normal alanine aminotransferase (ALT) levels. Although Dr. Winston cited a study in which 28% of primary care physicians said they would refer a patient with hepatitis C and normal ALT levels for treatment, he said normal ALT levels are not good indicators of disease severity. If patients are diagnosed with hepatitis C, Dr. Winston said physicians should immunize against HIV and hepatitis B, advise patients to not drink alcohol, review medications patients are taking, and inform patients that they should alert physicians about any new medications they are prescribed. When treating patients with hepatitis C, the goal is to permanently eradicate the virus from the serum, according to Dr. Winston. Clinicians are aiming for a sustained viral response (SVR), defined as an undetectable hepatitis C RNA 6 months after completing treatment. Dr. Watson said patients with an SVR have lower incidences of end-stage liver disease, hepatocellular carcinoma, and mortality. According to Dr. Watson, an SVR is found in 70% to 75% of patients who take the triple therapy of peginterferon and ribavirin with telaprevir or broceprevir. Before the recent approvals, when patients took peginterferon and ribavirin, 54% to 56% achieved an SVR. The efficacy of peginterferon and ribavirin differs depending on the genotype, with studies showing a 40% to 52% response rate for genotype 1 and an 80% to 93% response rate for genotype 2 or 3. Telaprevir and broceprevir are both direct-acting antivirals known as protease inhibitors. Dr. Watson said phase 3 trials indicated both drugs significantly increased SVR in treatment-naïve and treatment-experienced patients. Patients are advised to take two, 375-mg tablets of telaprevir every 7 to 9 hours with 20 g of fat in combination with peginterferon and ribavirin. Patients prescribed to take broceprevir begin treatment with 4 weeks of peginterferon and ribavirin, followed by the triple therapy of four, 200-mg broceprevir tablets every 7 to 9 hours with peginterferon, and ribavirin.