of Non-responders and Relapsers Treated with Pegylated
Interferon plus Ribavirin for Chronic Hepatitis C
Management of patients who do not achieve
sustained response to an initial course
of interferon-based combination therapy
for chronic hepatitis C virus (HCV) infection
remains a challenge, according to a review
article in the December
2009 Journal of Viral Hepatitis.
Fewer than 10% of non-responders benefit
from re-treatment, but the odds improve
with extended duration of pegylated interferon
plus ribavirin, and directly targeted anti-HCV
agents offer hope for the future.
than half of patients with hard-to-treat HCV genotype
1 achieve sustained
virological response (SVR) -- or a cure -- with
their first attempt at treatment with pegylated
interferon plus ribavirin.
"The probability of a previously treated patient
responding to re-treatment depends on the nature of
the previous regimen, the magnitude of the response
to previous treatment, and the patient's characteristics,"
wrote Douglas Dieterich from Mount Sinai School of
Medicine and colleagues.
In particular, relapsers (those who achieved undetectable
HCV RNA during treatment but experienced a rise in
viral load after completing therapy) have higher re-treatment
SVR rates, as do people who experienced partial response
(reduction but not clearance of HCV RNA) compared
with complete non-responders.
Re-treatment of non-responders using a standard 48-week
regimen of pegylated interferon alfa plus ribavirin
resulted in sustained response rates of about 6% in
program and about 8% in the REPEAT
trial. In REPEAT, however, the SVR rate was twice
as high -- 16% -- in those re-treated for 72 weeks
(P = 0.0006). "Based on available data,"
Dieterich and colleagues wrote, "extended treatment
is the best option for these individuals."
Undetectable HCV RNA at week 12 was an important predictor
of successful re-treatment in the REPEAT and EPIC
studies, as it is for initial therapy.
Based on disappointing results from trials such as
the review authors noted that, "Maintenance therapy
with pegylated interferon is generally ineffective
in non-responders and cannot be recommended."
Directly acting antiviral agents, such as the experimental
HCV protease inhibitors telaprevir
may increase sustained response rates in prior non-responders
and relapsers. However, these drugs have mostly been
studied in combination with interferon plus ribavirin
-- therefore adding to the burden of adverse events
-- and "will not be available for some years."
In conclusion, Dieterich and colleagues wrote, "after
careful evaluation of an individual's benefit-risk
ratio, a 72-week regimen is the preferred strategy
for optimizing sustained response rates in patients
who have not responded to the standard of care, provided
that viral RNA is undetectable at week 12 of re-treatment."
Mount Sinai School of Medicine, New York, NY; Division
of Gastro-Hepatology, Ospedale S. Giovanni Battista
(Molinette), Torino, Italy; Department of Gastroenterology,
Hepatology, and Endocrinology, Medical School Hannover,
DT Dieterich, M Rizzetto, and MP Manns. Management
of chronic hepatitis C patients who have relapsed
or not responded to pegylated interferon alfa plus
ribavirin. Journal of Viral Hepatitis 16(12):