Genotype 1 Hepatitis C Patients Can Be Cured with 24 Weeks of
Telaprevir plus Pegylated Interferon/ribavirin
Forns from the University of Barcelona and an international
team of colleagues conducted an open-label Phase 2 trial evaluating
telaprevir in combination with the standard regimen of pegylated
interferon plus ribavirin in people with hard-to-treat HCV genotype
1 who had not received prior interferon-based therapy.
Study C208 included 161 participants in several European countries.
About half were men, 90% were white, the mean age was about
45 years, about 20% had advanced fibrosis or cirrhosis, and
approximately 80% had high baseline HCV RNA (> 800,000
Participants were randomly allocated to 4 treatment arms, receiving
telaprevir at doses of either 750 mg 3 times daily (every 8
hours) or 1125 mg twice daily (every 12 hours), along with pegylated
interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b
(PegIntron) plus weight-adjusted ribavirin. Patients took
telaprevir for 12 weeks and then continued pegylated interferon/ribavirin
for at least an additional 12 weeks.
In a response-guided design, patients who achieved rapid virological
response (RVR) at week 4 and maintained undetectable viral load
(< 25 IU/mL) through week 20 stopped treatment at 24 weeks,
while those who did not meet these criteria received pegylated
interferon/ribavirin for 48 weeks.
The main finding of Study C208 was that 80%-85% of patients
across treatment arms achieved sustained virological response
(SVR), or undetectable HCV viral load 24 weeks after completing
therapy. At EASL the investigators presented data from a sub-analysis
of efficacy according to dosing schedule and type of pegylated
of participants had undetectable HCV RNA from week 4 through
20 and were therefore eligible to stop therapy at 24 weeks.
required treatment for 48 weeks.
discontinued treatment before week 24 due to virological
failure, adverse events, or for other reasons.
in an intent-to-treat analysis, sustained response rates
were high regardless of how often people took telaprevir
or which type of pegylated interferon they used:
8 hours with Pegasys: 85%;
8 hours with PegIntron: 81%;
12 hours with Pegasys: 83%;
12 hours with PegIntron: 82%;
who achieved RVR and were treated for 24 weeks did better
than those without SVR who were treated for 48 weeks (96%
vs 79%, respectively).
of viral breakthrough during treatment and relapse after
treatment completion were low (14 and 9 participants, respectively).
of adverse event were similar across treatment arms.
most common adverse events were skin rash and pruritus (itching).
of participants discontinued therapy due to adverse events,
most often rash.
majority of patients (68%) qualified to receive 24 weeks of
total treatment duration ([due to] undetectable HCV RNA from
week 4 through week 20)," the researchers concluded.
"Among these, a high proportion (93%-100%) achieved a SVR,
regardless of pegylated interferon type or telaprevir dosing
schedule," they added. "Continuing pegylated interferon/ribavirin
beyond 24 weeks resulted in high SVR rate in patients that did
not meet criteria for shorter treatment."
Liver Unit, University of Barcelona, Barcelona, Spain; Hôpital
Beaujon, Clichy, France; Department of Internal Medicine, Medical
University of Vienna, Vienna, Austria; Klinikum der Universität
zu Köln, Cologne, Germany; Department of Hepatology, University
Hospital Gasthuisberg, Leuven, Belgium; Clinic of Infectious
and Tropical Diseases, University of Brescia, Brescia, Italy;
Radboud University Nijmegen Medical Center, Nijmegen; Netherlands;
Hôpital St Antoine, Paris, France; Tibotec BVBA, Mechelen,
Belgium; Tibotec Inc, Yardley, PA.
X Forns, P Marcellin, P Ferenci, and others. On-treatment response-guided
therapy with telaprevir q8h or q12h combined with peginterferon
alfa-2a or peginterferon alfa-2b and ribavirin in treatment-naive
genotype 1 hepatitis C (Study C208). 45th Annual Meeting of
the European Association for the Study of the Liver (EASL 2010).
Vienna, Austria. April 14-18, 2010. (Abstract