In November 2012, investigators from the Office of Public Health (OPH) in the U.S. Department of Veterans Affairs (DVA) reviewed patient data from a large group of veterans infected with genotype 1 hepatitis C virus (HCV) infection. This type accounts for approximately 70% of HCV patients. The study focused on patient responses to more recently approved direct-acting antiviral drugs (DAAs). Findings were presented during the 63rd Annual Meeting of the American Association for the Study of Liver Diseases in Boston, MA, November 9-13, 2012. The lead investigator of the study was Lisa Backus, MD, PhD, from OPH in the DVA and in the Veterans Health Administration in Palo Alto, CA.
In May 2011 the U.S. Food and Drug Administration (FDA) approved two DAAs: Merck’s boceprevir under the brand name Victrelis™ and Vertex Pharmaceutical’s telaprevir under the brand name Incivek™. Representing the first new HCV therapies in 10 years, Victrelis™ and Incivek™ are protease inhibitors that work by thwarting the replication of viral enzymes. These drugs augment the current standard of treatment, which combines weekly injections of pegylated interferon (P-IFN) and a daily ribavirin (RBV) oral pill. New drugs are needed to treat HCV because nearly 50% of patients do not respond to the current combination therapy alone. Even patients who do respond often experience debilitating side effects that can last the duration of the treatment—either 24 or 48 weeks.
Earlier clinical studies of telaprevir and boceprevir were carefully controlled with very strict eligibility criteria. Backus and her colleagues therefore sought to determine how well the drugs performed in a “real world” environment by examining the results from routine practice at DVA, the largest provider of healthcare to HCV patients in the U.S.
Culling from the Veterans Affairs Clinical Case Registry, Backus and her team identified 859 patients infected with HCV genotype 1. The majority were white men whose mean age was 57. In addition to a regimen of P-IFN and RBV, 661 patients received boceprevir and 198 received telaprevir. Cirrhosis had been diagnosed in 24% of the boceprevir group and 41% of the telaprevir group.
After 24 weeks of therapy, the overall virologic response rate was 69% in the boceprevir group and 64% in the telaprevir group. Patients with cirrhosis had slightly lower response rates in the boceprevir and telaprevir groups (64% vs. 60%), and previous nonresponders to treatment did the poorest, 44% vs. 53%.
At the end of treatment, the overall response rate was 60% in the boceprevir group and 55% in the telaprevir group. Backus qualified the findings, explaining that the results reported are considered an interim analysis because the researchers do not yet have sustained virological response (SVR) data and some patients have not reached the end of treatment. Success in HCV treatment is typically measured by a patients’ ability to “clear” the virus by achieving SVR for at least six months after completing therapy. Though not technically a cure--HCV is often not completely eradicated from the liver--SVR is still the goal for clinicians. Lowering the viral load to undetectable levels in the bloodstream decreases the disease’s most harmful effects.
Backus and her colleagues expressed confidence that the high rates of undetectable HCV levels at the end of therapy would eventually lead to SVR rates that are higher than those seen prior to the availability of DAAs.
Source: Medscape.com, November 30, 2012