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Robert Brown MD:
Patients who do not receive a sustained virologic response are generally
grouped into two groups. One is relapsers, i.e., those patients who became
negative during therapy but in whom the virus reappears after therapy
has stopped in between the end of therapy and six months following therapy.
The second group are patients who are called non-responders, who never
became virologically negative. Some people will subgroup those non-responders
into partial responders and complete non-responders, though the significance
of those two groups is less clear than the difference between relapsers
and non-responders.
The options for partial responders in terms of treatment depend on what
you are a partial responder to. Patients who are partial responders to
interferon monotherapy are often a candidate for combination therapy though
patients who are non-responders to combination therapy the data is not
clear. There are some studies of pegylated interferon and ribavirin for
patients who did not respond to standard interferon and ribavirin. The
response rates have been about 25% though the data has not yet been published.
Rajender Reddy MD:
Nonresponders are obviously a difficult to treat population, and as of
the current time we do not have any defined treatments for nonresponders
to pegylated interferons and ribavirin. However if patients had quite
significant fibrosis and even cirrhosis but are in a well-compensated
state, the question comes up whether maintenance therapy can be of some
value to these patients. However, there are no defined guidelines on the
role of maintenance therapy, and also it is not clear as to how long one
would need to continue maintenance therapy, what are the endpoints for
such therapy and so on?
Robert Brown MD:
Re-treatment of prior non-responders is a controversial topic. There are
a lot of non-responders out there and the first question that has to be
asked is what were they a non-responder to? Patients who are non-responders
to interferon-based monotherapy are probably good candidates for re-treatment
with pegylated interferon and ribavirin. Patients who were non-responders
to interferon and ribavirin combination therapy are less likely to respond
to pegylated interferon and ribavirin combination therapy. Though in patients
who became negative and then relapsed after therapy, a longer course of
therapy may be more advantageous, though I don't think that patients who
never became negative on their initial course of therapy are likely to
get a sustained virologic response to a longer course of re-treatment.
David Bernstein MD:
Patients who are non-responders to pegylated interferon and ribavirin
and don't have cirrhosis should probably wait and be treated in a clinical
trial with newer therapies when they become available. Patients that have
underlying cirrhosis and have a positive viral test at the end of therapy
may be considered for maintenance treatments, although maintenance treatments
are unapproved and currently under study.
What are the best treatment strategies for partial and incomplete responders
or relapsers?
Robert Brown MD:
The treatment of patients who fail a course of interferon monotherapy
or combination therapy with interferon and ribavirin is controversial.
Clinical studies are underway, and the answer should be available in the
next one to two years, but at the current time, we're left with clinical
judgment.
My approach to treating interferon non-responders is to offer all those
patients a course of pegylated interferon and ribavirin combination therapy.
I think our response rates will not be too dramatically different from
the naïve population due to the low response rate to interferon monotherapy.
Pegylated interferon and ribavirin combination therapy will be most effective
in the patients who have relapsed after interferon and ribavirin therapy
and will be progressively less effective in patients who had either a
partial response or a complete non-response to an initial course of interferon
and ribavirin combination therapy.
How does genotype affect treatment of non-responders?
Robert Brown MD:
When you look to re-treatment of non-responders, genotype becomes much
less important as a predictor of response to re-treatment since the majority
of patients will be genotype 1. If you start with 70% genotype 1, and
80% of the genotype 2/3 patients will have responded to standard interferon
and ribavirin, you're not going to have a lot of genotype 2/3 patients
left.
When you look at the re-treatment response rates by genotype, I don't
think we have enough data on the genotype 2/3 patients to make a clear
conclusion about what the re-treatment rates will be. When we re-treat
the patients, regardless of genotype, we re-treat them all the same because
they have shown themselves to be prior non-responders. So these patients
would all get a full dose of ribavirin and a full course of therapy over
48 weeks.
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