July 3, 2011

Telaprevir Markedly Improves HCV Genotype 1 Cure Rates

Summary and Comment

Final results of phase III trials show that telaprevir plus standard therapy with peginterferon alfa-2a and ribavirin was more effective than standard therapy alone.

Recently, telaprevir-based triple therapy (i.e., in combination with peginterferon alfa-2a and ribavirin) was approved for the treatment of chronic hepatitis C virus (HCV) infection. The final results of the international phase III trials for both treatment-naive and treatment-experienced patients with HCV genotype 1 infection are now available.

In the first of two industry-sponsored, double-blind, placebo-controlled trials, 1095 treatment-naive patients were randomized to receive either triple therapy for 12 weeks followed by peginterferon plus ribavirin for 12 weeks — or 36 weeks if HCV RNA was detectable at weeks 4 or 12 — (T12PR group); triple therapy for 8 weeks followed by peginterferon plus ribavirin for either 16 or 36 weeks (T8PR group); or peginterferon plus ribavirin for 48 weeks (PR group).

In the second trial, 663 treatment-experienced patients were randomized 2:2:1 to receive either triple therapy for the first 12 weeks followed by 36 weeks of peginterferon plus ribavirin (T12PR48 group), a 4-week lead-in of peginterferon plus ribavirin followed by 12 weeks of triple therapy and then 32 weeks of peginterferon plus ribavirin (lead-in T12PR48 group), or peginterferon plus ribavirin for 48 weeks (PR48 group). In both trials, doses were 750 mg every 8 hours for telaprevir, 180 µg weekly for peginterferon alfa-2a, and 1000–1200 mg daily for ribavirin. The primary endpoint was sustained virologic response (SVR).

For treatment-naive patients, SVR rates were higher in the T12PR and T8PR groups than in the PR group — 75% and 69% versus 44%; P<0.001. Although the numbers of patients who were black or had advanced fibrosis were small in the study cohort (7% and 20%, respectively), in both subgroups, SVR rates were higher in the telaprevir groups than the peginterferon plus ribavirin group.

Among treatment-experienced patients, SVR rates for arms T12PR48, lead-in T12PR48, and PR48, respectively, were 83%, 88%, and 24% for previous relapse; 59%, 54%, and 15% for previous partial response; and 29%, 33%, and 5% for previous null response (P<0.001 for all comparisons). In general, virologic failure in the telaprevir groups was attributable primarily to the development of drug resistance. In both studies, the telaprevir groups had higher rates of anemia, rashes, pruritus, and gastrointestinal problems than the peginterferon plus ribavirin group. Discontinuation of medications for any reason ranged from 10% to 15% for the telaprevir regimens and from 7% to 10% for the peginterferon plus ribavirin regimen.

Comment: These companion studies demonstrate that telaprevir-based regimens are significantly more effective in HCV genotype 1–infected patients than peginterferon plus ribavirin alone — for both treatment-naive and treatment-experienced patients. Although more adverse events occurred in the telaprevir-treated groups, discontinuation rates were still relatively low. Overall, the best SVRs were seen in treatment-naive and prior-relapse patients (75%), followed by previous partial responders, treatment-naive blacks, and patients with advanced fibrosis (50%–60%), and last, previous null responders (30%). Therefore, caution should be exercised in treating null responders, especially since the majority of virologic failure leads to drug resistance.

Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology July 1, 2011

Citation(s):

Jacobson IM et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011 Jun 23; 364:2405.
Medline abstract (Free)

Zeuzem S et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011 Jun 23; 364:2417.
Medline abstract (Free)

No comments:

Post a Comment