Daniel M. Keller, PhD

November 30, 2012

BOSTON — In a study of veterans infected with hepatitis C virus (HCV) genotype 1, the direct-acting antiviral drugs boceprevir and telaprevir, in combination with pegylated interferon and ribavirin, produced robust antiviral responses at 24 weeks and at the end of therapy.

"The end-of-treatment response rates basically look the same [for boceprevir and telaprevir] in any of the subgroups we looked at," lead researcher Lisa Backus, MD, PhD, from the Office of Public Health in the US Department of Veterans Affairs and in the Veterans Health Administration in Palo Alto, California, told Medscape Medical News.

We found that previous null responders have very low response rates, so they "do the worst, previous partial responders do better, and previous relapsers have the highest response rates," she explained here at The Liver Meeting 2012: American Association for the Study of Liver Diseases 63rd Annual Meeting.

The results reported are considered an interim analysis because the researchers do not yet have sustained virologic response data and some patients have not reached the end of treatment, Dr. Backus explained.

Previous virologic response rates with these direct-acting antiviral drugs were derived from clinical trials with strict inclusion criteria. To evaluate how well these drugs work in the real world, Dr. Backus and colleagues examined routine practice in the Department of Veterans Affairs, the single largest provider of healthcare to HCV-infected people in the United States.

From the Veterans Affairs Clinical Case Registry, the researchers identified 859 patients infected with HCV genotype 1. In addition to a regimen containing pegylated interferon and ribavirin, 661 patients received boceprevir and 198 received telaprevir. Patients with hepatitis B virus, HIV co-infection, or hepatocellular carcinoma were excluded from the analysis, as were those who had undergone liver transplantation.

The study population was about 95% men, 60% white, 25% to 30% black, and the mean age was 57 years. Cirrhosis was present in 24% of the boceprevir group and 41% of the telaprevir patients. In the boceprevir group, 59% were treatment-naive, 10% were previous null responders, 11% were previous partial responders, and 18% were previous relapsers. In the telaprevir group, 49% were treatment-naive, 19% were previous null responders, 14% were previous partial responders, and 17% were previous relapsers. At the time of the analysis, 532 patients in the boceprevir group and 160 in the telaprevir group had ended therapy.

Robust Virologic Responses With Both Drugs

After 24 weeks of therapy, the overall virologic response rate was 69% in the boceprevir group and 64% in the telaprevir group (P = .15). There were no statistically significant differences between the boceprevir and telaprevir groups in response rates for any of the subgroups, according to previous response, except for treatment-naive noncirrhotic patients (74% vs 60%, respectively; P = .03). Cirrhotic patients had slightly lower response rates in the boceprevir and telaprevir groups (64% vs 60%), and previous null responders did the poorest (44% vs 53%).

Total treatment duration depended on whether the treatment was new, previous responses, the presence or absence of cirrhosis, and the detectability of HCV RNA at interim time points. Accordingly, treatment could range from 24 to 48 weeks.

At the end of treatment, the overall response rate was 60% in the boceprevir group and 55% in the telaprevir group (P = .25). Treatment-naive noncirrhotic patients had response rates of 66% and 60%, respectively. For all cirrhotic patients, the response rates were 49% and 45%, respectively. None of these differences between the drugs was significant.

For noncirrhotic and cirrhotic patients together, previous null responders had the poorest responses to retreatment, and there was no difference between the 2 drugs.

End-of-Treatment Virologic Response Rates (Undetectable HCV RNA)

Patient Type Boceprevir, % Telaprevir, % P value
Previous null responder 19 26 .46
Previous partial responder 59 62 .83
Previous relapser 67 85 .08

Adverse-events data were not reported, but Dr. Backus said that the rates of adverse events "look fairly similar between the people who got boceprevir and the people who got telaprevir" out to week 12.

Patients in routine medical practices in the Veterans Affairs health system treated with either boceprevir or telaprevir had robust virologic responses at 24 weeks and at the end of therapy. Cirrhotic patients and previous null responders tended to have lower response rates. The researchers predict that the high rates of undetectable HCV RNA at the end of therapy might lead to sustained virologic responses higher than those seen in veterans before direct-acting antiviral drugs were introduced.

David Wong, MD, clinical director of the Liver Centre at the Toronto Western Hospital and director of hepatology education the University of Toronto, Ontario, Canada, told Medscape Medical News that if telaprevir and boceprevir are used in inappropriate patients, such as those with decompensated cirrhosis, they can get very sick.

He explained that newer drugs in development have already shown excellent responses and are starting to be tested in harder-to-treat patients with cirrhosis. Many of those drug combinations do not involve interferon. "Interferon-free regimens are going to be a lot better tolerated and hold more hope for us," he said.

"My bet is [that boceprevir or telaprevir] won't be used with interferon-free [regimens] because there are other protease inhibitors that are much easier to use," Dr. Wong said. "These have high pill burdens and side effects, whereas the newer ones — the TMC molecule [TMC-435; Tibotec Pharmaceuticals] and the [Boehringer Ingelheim] protease inhibitors — are once-daily dosing, so [are] much more convenient."

As for regimens based on boceprevir or telaprevir, "I think they've got a year or so" to go, depending on approval of the interferon-free regimens in development, he said.

There was no commercial support for the study. Dr. Backus and Dr. Wong have disclosed no relevant financial relationships.

The Liver Meeting 2012: American Association for the Study of Liver Diseases (AASLD) 63rd Annual Meeting. Abstract LB-30. Presented November 12, 2012.