Shorter duration telaprevir therapy effective in HCV

Telaprevir for 12 weeks, in addition to 24 weeks of treatment with peginterferon and ribavirin, is noninferior to 12 weeks of treatment with telaprevir plus 48 weeks of treatment with peginterferon and ribavirin. September 14, 2011 — In patients with chronic hepatitis C virus (HCV) genotype 1 infection, telaprevir for 12 weeks, in addition to 24 weeks of treatment with peginterferon and ribavirin, is noninferior to 12 weeks of treatment with telaprevir plus 48 weeks of treatment with peginterferon and ribavirin, according to findings of a phase 3 clinical trial.

Kenneth E. Sherman, MD, PhD, with the Division of Digestive Diseases, at the University of Cincinnati College of Medicine, in Cincinnati, Ohio, and colleagues reported their findings in the September 15 issue of the New England Journal of Medicine.

Telaprevir is an orally bioavailable inhibitor of the nonstructural 3/4A (NS3/4A) HCV protease. The researchers note that "a response-guided treatment regimen based on viral response may permit a shorter treatment duration while preserving high rates of sustained virologic response." The current study compared the safety and efficacy of response-guided therapy with 24-week vs 48-week treatment regimens of peginterferon/ribavirin in combination with telaprevir.

A total of 540 patients with chronic HCV genotype 1 infection who had received no prior treatment were given study drugs at 74 sites included in the trial. For the first 12 weeks, the patients were given 750 mg of telaprevir every 8 hours, 180 µg of peginterferon alfa-2a once per week, and 1000 to 1200 mg of ribavirin per day.

After week 12, telaprevir administration was stopped in all patients, and they continued to receive peginterferon and ribavirin only. After week 20, patients who had demonstrated extended rapid virologic response (whose HCV RNA levels had been undetectable at weeks 4 and 12) were randomly assigned to receive peginterferon and ribavirin for either 4 more weeks or 28 more weeks, whereas patients who did not show extended rapid virologic response received the 2 drugs for 28 more weeks.

The noninferiority trial compared rates of sustained virologic response in the group receiving peginterferon and ribavirin for 4 more weeks vs the group receiving the same drugs for 28 more weeks and established the noninferiority of the shorter treatment regimen.

Noninferiority Demonstrated

Overall, the rate of sustained virologic response was 72%. Among the 322 patients with an extended rapid virologic response who were randomly assigned to a study group, 92% in the 24-week group vs 88% in the 48-week group had a sustained virologic response, indicating noninferiority with respect to efficacy in the 2 groups.

Adverse effects led 18% of study patients to discontinue treatment, but only 1% in the 24-week group discontinued vs 12% in the 48-week group (P < .001). Adverse events included rashes in 37% of patients and anemia in 39%.

"In our phase 3 study, 24 weeks of peginterferon and ribavirin treatment was noninferior to 48 weeks of treatment for patients infected with HCV genotype 1 who had not previously received treatment and who had undetectable HCV RNA levels at weeks 4 and 12," Dr. Sherman and colleagues conclude.

According to the researchers, this study supports the concept of response-guided therapy. "Relapse rates were low and were not significantly different between the 24-week group and the 48-week group," they write.

"In addition, response-guided therapy also resulted in decreased rates of adverse events and treatment discontinuation among patients who received treatment over the shorter period," they note.

Comment : Rapid Response May Be the Key

According to independent commentator David L. Thomas, MD, MPH, chief of infectious diseases at the Johns Hopkins School of Medicine in Baltimore, Maryland, these data "demonstrate that the two-thirds of persons who rapidly respond to treatment with peginterferon alfa, ribavirin, and telaprevir can effectively cut the duration of treatment in half."

"This finding, combined with the much greater success of treatment in those who took the HCV protease inhibitor compared to placebo, underscore just how far HCV treatment has advanced this summer," Dr. Thomas told Medscape Medical News.

"These findings and those for boceprevir, the other approved HCV protease inhibitor, should encourage all providers to test all their patients who might be at risk of HCV for infection and to engage all who are positive in a serious discussion as to whether treatment is right for them now," he said. "Even those who end up deciding to wait will want to be treated in the next few years, and it is crucial to get them into care."

The study was supported by Vertex Pharmaceuticals and Tibotec. Disclosure forms provided by the study authors are available with the full text of this article on the New England Journal of Medicine Web site.Dr. Thomas states that he is on the advisory board for Merck, the maker of boceprevir.

By Emma Hitt, PhD

N Engl J Med. 2011 ;365:1014-1024.

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