New data published in a major peer-reviewed journal, Annals of
Internal Medicine, show that re-treatment with Pegasys(R) (peginterferon
alfa-2a) plus Copegus(R) (ribavirin) provides previously-treated hepatitis
C
patients a second chance for a cure. The study results demonstrated that
patients most likely to respond to re-treatment could be identified after
only 12 weeks, allowing patients and their doctors to be confident early
on
about the likelihood of success.(1)
"While tremendous advances in hepatitis C treatment have cured many
hepatitis C patients, a significant proportion of patients do not achieve
success with their first treatment course. This is leading to a large and
growing population of patients who are in urgent need of alternative
treatment options," said Donald Jensen, US principal investigator for
REPEAT,
and Professor of Medicine and Director of the Center for Liver Diseases at
the University of Chicago Hospital in Chicago. "With 72 weeks of Pegasys
and
ribavirin combination treatment as a new solution for those with the most
difficult-to-treat form of the virus, patients can now feel more hopeful
that
they have the possibility to achieve a cure when previous therapy has
failed."
Pegasys (peginterferon alfa-2a) received European Commission approval
for
the re-treatment of hepatitis C in December 2008, based in part on results
of
the newly-published study. For patients with genotype 1 virus who were
initially treated with pegylated interferon and ribavirin, it is
recommended
that they be retreated with peginterferon alfa-2a for an extended period
of
72 weeks. Peginterferon alfa-2a is now the first and only pegylated
interferon to be approved anywhere for treatment of up to 72 weeks. For
all
other previously-treated patients, the recommended treatment period is 48
weeks.
The Need for Re-treatment Options
The standard of care for patients with chronic hepatitis C is the
combination of a pegylated interferon plus ribavirin. In hepatitis C,
sustained virologic response (SVR) to interferon-based treatment is widely
equated to cure(2) as it is associated with eradication of HCV infection
and
improvement in liver disease. Approximately 50% of patients with genotype
1,
the most difficult to treat form of the disease, and 20-30% of patients
with
genotypes 2 or 3 do not achieve a cure after a first course of therapy.(1)
The REPEAT Study
Enrolling 950 patients from Europe, North America and Latin America,
the
REPEAT (REtreatment with PEgasys in pATients Not Responding to Peg-Intron
Therapy) study was designed to explore whether intensified treatment with
a
higher initial dose of Pegasys (peginterferon alfa-2a) in combination with
ribavirin, and/or longer treatment duration, may increase treatment
success
rates in patients who didn't respond to at least twelve weeks of
PegIntron(TM) (peginterferon alfa-2b) plus ribavirin and who didn't
discontinue treatment due to haematological adverse events.
The results demonstrated that while a fixed-dose induction did not
contribute to treatment success, patients receiving 72 weeks of
re-treatment
with peginterferon alfa-2a doubled the chance of achieving a cure compared
with the previous standard of 48 weeks (16% vs. 8%). Furthermore, the
study
showed that for the 17% of patients who responded by week 12 (defined as
HCV
RNA levels of less than 50 IU/mL), 57% went on to achieve a cure after a
72-week treatment course, compared with only 35% of patients who were
re-treated for 48 weeks.
"It is a significant step forward that we now know patients who have
undetectable levels of hepatitis C at week 12 have a good likelihood of
achieving a cure with Pegasys and ribavirin. This ability to predict
success
after just three months will give both doctors and hepatitis C patients
additional confidence when considering whether to re-treat," said
Professor
Jensen.
Treatment with peginterferon alfa-2a plus ribavirin was well tolerated
in
the study. The adverse event profile was similar to that seen in patients
treated for the first time. Further analyses of the 72-week treatment
duration in REPEAT showed that it was associated with a more favourable
benefit:risk ratio than 48 weeks of treatment.(3) The most common side
effects of treatment were flu-like symptoms, fatigue, depression and
haematological abnormalities.
References
(1) Jenson DM, Marcellin P, Bradley F et al. Re-treatment of chronic
hepatitis C non-responders to peginterferon alfa-2b: a randomized trial.
Annals of Internal Medicine 2009;150(8):528-540.
(2) Swain M, Lai M, Shiffman M, Cooksley W et al. Sustained virologic
response (SVR) resulting from treatment with peginterferon alfa-2a (40KD)
(Pegasys(R)) alone or in combination with ribavirin (Copegus(R)) is
durable
and constitutes a cure: an ongoing 5-year follow-up. Abstract presented at
Digestive Disease Week; 21 May 2007; Los Angeles, California, USA.
(3) Marcellin P. et al. A 72-week treatment duration with peginterferon
alfa-2a (40KD) (PEGASYS(R)) plus ribavirin (COPEGUS(R)) has a favorable
risk:benefit ratio in non-responders to pegylated interferon alfa-2b
(12KD)
plus ribavirin: findings of the multinational REPEAT study. Poster
(PO1873)
presented at Annual Meeting of the American Association for the Study of
Liver Diseases (AASLD); 31 October - 4 November 2008; San Francisco,
California, USA.
Source
Roche
View drug information on Peg-Intron; Pegasys.