International Consortium Exploring Long-term Outcomes of Treating Hepatitis C Releases First Data

Two antiviral drugs used to treat hepatitis C appear to work as well in the real world as they did during clinical trials, an international research consortium has observed. The consortium also released data that may help inform how doctors and patients manage treatment-related adverse events.

The international effort, known as HCV-TARGET, follows how newly approved therapies for hepatitis C are used and managed in routine practice. It is led jointly by the University of Florida and the University of North Carolina at Chapel Hill. The ongoing research suggests that the safety and efficacy of the antiviral drugs telaprevir and boceprevir are similar for North American patients taking the treatments in real-world settings to what was observed in clinical trials.

The international effort, known as HCV-TARGET, follows how newly approved therapies for hepatitis C are used and managed in routine practice. It is led jointly by the University of Florida and the University of North Carolina at Chapel Hill. The ongoing research suggests that the safety and efficacy of the antiviral drugs telaprevir and boceprevir are similar for North American patients taking the treatments in real-world settings to what was observed in clinical trials.

The evaluation of data available from November 2011 through April 2013, presented at the 48th Annual Meeting of the European Association for the Study of the Liver in Amsterdam, found that anemia was the most relevant adverse event affecting clinical care. Approximately two-thirds of anemic patients were managed with drug dose reductions, which minimized the need for expensive growth factors and blood transfusions. The analysis also reveals that patients with cirrhosis were at increased risk for treatment-related complications, including severe anemia and significant deterioration of the liver, which often resulted in stopping therapy early.

"We plan to track up to 5,000 patients internationally over five years to continue to assess the benefits and risks of new treatments in real-world settings," said co-PI Michael W. Fried, MD, professor of medicine at UNC, which serves as the HCV-TARGET data coordinating center. "HCV-TARGET serves as a model for cross-cutting collaborative studies that can rapidly advance knowledge in an important illness of public health concern."

"This is a long-term study, and we plan to release similar interim analyses each spring and fall to provide clinicians with up-to-date knowledge that can inform how we manage therapy for patients with hepatitis C," said co-PI David R. Nelson, MD, director of the UF Clinical and Translational Science Institute and professor of medicine at UF, which serves as the clinical coordinating center for HCV-TARGET.

One of the consortium’s priorities for future analyses will be to investigate indicators that may predict adverse outcomes in cirrhotic patients and guide safer use of these drug regimens.Hepatitis C is a viral liver disease transmitted through contact with an infected person’s blood. Chronic hepatitis C can lead to serious liver problems including liver damage, cirrhosis, liver failure or liver cancer. Because a person with chronic hepatitis C can live symptom-free for many years, many people do not know they are infected.

Globally, the World Health Organization estimates about 150 million individuals are chronically infected with hepatitis C, and more than 350,000 people die each year from hepatitis C-related liver diseases. In the U.S., the Centers for Disease Control and Prevention estimates 3.2 million people are chronically infected with hepatitis C, although a 2011 review article in Liver International suggests the estimate is likely higher – at least 5.2 million people – if U.S. populations not surveyed by the CDC are included, such as the homeless and incarcerated.

HCV-TARGET is an international research consortium created to inform the ongoing transformation of hepatitis C treatment and research. The HCV-TARGET model is rooted in the infrastructure and collaborative network developed through the National Institutes of Health’s Clinical and Translational Science Award (CTSA) program, which is led by the National Center for Advancing Translational Sciences. In addition to UNC and UF, HCV-TARGET includes 23 other CTSA-supported institutions among its 103 academic and community sites in 31 states, Puerto Rico, Canada and Europe. HCV-TARGET also partners with multiple industry sponsors, regulatory agencies and the patient advocacy community.

In 2011, HCV-TARGET established a nationwide registry to observe patients in the United States undergoing hepatitis C treatment over time and to coordinate real-world monitoring on a national scale for new therapies as they enter the market. For patients who agree to be in the study, the project is capturing demographic, clinical, adverse event and virological data. To date approximately 1,900 patients have agreed to participate, including patients with cirrhosis and other populations underrepresented in clinical trials.

"The data coming out of the HCV-TARGET consortium will help inform physicians and patients as they weigh important decisions regarding therapy, decisions that can greatly impact quality of life," said Donald M. Jensen, M.D., professor of medicine at the University of Chicago and a member of the HCV-TARGET Steering Committee. HCV-TARGET’s participating patients are treated according to local standards of care. In addition, participants can allow HCV-TARGET to collect their whole blood for DNA and serum and store it at a central biorepository for future research.

The network’s initial study has followed a broad population of adult patients in North America treated with telaprevir or boceprevir, which were newly approved by the U.S. Food and Drug Administration when HCV-TARGET launched. In 2013, HCV-TARGET is expanding its study to include European sites and patients treated with any direct-acting antiviral agent approved by the FDA.

HCV-TARGET receives ongoing industry support from Merck, Genentech, Kadmon, and Vertex. Dr. Fried receives research grant support and serves as ad hoc consultant to Genentech, Vertex, Merck, Gilead, Bristol Myers Squibb, Janssen and Abbott. Dr. Nelson receives grant support from Genentech, Kadmon, Merck, Vertex Pharmaceuticals, Gilead, Boehringer Ingelheim and Abbott/Abbvie; and payment for the development of educational presentations from Clinical Care Options, Rush University Medical Center, Practice Point Communications and Chronic Liver Disease Foundation.