Clinical

Telaprevir regimens improve treatment of chronic HCV infection

Last Updated: 2009-04-29 17:00:14 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In treating chronic infection with hepatitis C virus (HCV), higher sustained virologic response rates are seen when the drug regimen includes telaprevir, an HCV-specific protease inhibitor, according to the results of the PROVE1 and PROVE2 studies reported in The New England Journal of Medicine for April 30.

In early studies, treatment with telaprevir has been shown to cause a rapid drop in HCV RNA levels, but whether its addition to currently used agents could improve response rates was unclear, Dr. John G. Hutchison, from Duke University Medical Center, Durham, North Carolina, and colleagues note.

In PROVE1 (Protease Inhibition for Viral Evaluation 1), Dr. Hutchison's team assessed the outcomes of 263 patients with chronic infection with HCV genotype 1 who were randomized to receive telaprevir for 12 weeks in combination with peginterferon and ribavirin for 12, 24, or 48 weeks or just peginterferon and ribavirin for 48 weeks (control).

The main outcome measure was the sustained virologic response, defined as no detectable HCV RNA at 24 weeks after the end of treatment.

The sustained virologic response rate in the control group was 41% compared with rates of 61% and 67% in the telaprevir groups that received peginterferon and ribavirin for 24 and 48 weeks, respectively. The rate in the telaprevir group that received peginterferon and ribavirin for 12 weeks was just 35%, but the authors state that this group was strictly exploratory and not compared with the control group.

Viral breakthrough was noted in 7% of telaprevir-treated patients. The treatment discontinuation rate in the combined telaprevir groups was 21% compared with 11% in the control group. Rash was the most common reason for stopping therapy.

In PROVE2, Dr. Jean-Michel Pawlotsky, from Hopital Henri Mondor, Creteil, France, and colleagues assessed the outcomes of 334 patients who were randomized to a 48-week peginterferon/ribavirin control group or to groups that combined 12 weeks of telaprevir with 12 or 24 weeks of peginterferon/ribavirin or 12 weeks of only peginterferon.

The authors found that 12 weeks of telaprevir-based therapy achieved a comparable sustained virologic response rate as 48 weeks of peginterferon/ribavirin, hovering around 47%.

The findings also indicate that response rates in the telaprevir groups were higher when ribavirin was included in the regimen. The groups that included ribavirin for 12 and 24 weeks had response rates of 60% and 69%, respectively, compared with a rate of just 36% in the group that did not use this agent.

"Telaprevir appears to be a material advance in the therapy of hepatitis C, beginning a new era of treatment--an era of antiviral agents developed specifically to target this virus," Dr. Jay H. Hoofnagle, from the National Institutes of Health, Bethesda, Maryland, comments in a related editorial.

N Engl J Med 2009;360:1827-1850,1899-1901.