Haematologica 2000;85:supplement to no. 10 - Supplements ...

Immune Tolerance and the Treatment of Hemophilacs with an Inhibitor 43
clonal you implied that the differences would go
away rather than the fact that they might
expand. I think that since you showed us that all
the characteristics that the other registries
showed as benefits to success were all in the
opposite direction specifically if it is more likely
that the monoclonals will be better than the
recombinant rather than the reverse. Therefore,
I wasn’t sure that I understood your final comment
that more people will use recombinant for
immune tolerance if the data don’t support
that. I think it would be folly because it’s a lot
more expensive. I’d like to understand better
your logic in that particular situation.
DI MICHELE: In terms of the definition issues
that has always been an important difference
between the registries, iIt’s interesting that when
we look at the same predictors of success and
non-success, despite the fact that definitions of
success were quite variable in the North American
Registry, I think it is amazing that a lot of the
same success parameters and outcome parameters
continued to hold up regardless of that
definition. I can’t comment any further on that
because the definitions are the definitions. With
respect to your comments on the possible differences
between recombinant and monoclonal
concentrates I think that this difference might
go away as the data are few and the P Value is
0.04. This was significant but now it has only
borderline significance. Therefore it is possible
that as we get more data and the numbers
become real, this difference may disappear. So,
I don’t know which way it is going to go and I
think the important thing is that you can’t overinterpret
these preliminary data. Consequently,
I don’t think people should be making choices of
product based on the preliminary data.
HULMAN. You found a poor difference
between the recombinant and the monoclonal
products. Are you quite sure that the dosage was
the same in these two groups The German Registry
is very old. We started therapy following
the Bonn protocol twenty five years ago and that
is an era without any recombinant products. We
started this with intermediate products and the
success at that time was about eighty percent as
Dr.Lenk has shown. Are you sure we could do
better with monoclonal products
DI MICHELE: No, I’m not sure. I’m raising this
as an important issue because in the past we’ve
discussed product with respect to purity. We
have not looked at products of similar purity
and overall success rates. I think it is very important
that we continue looking at this issue in
order to become more sure about issues such
as outcome prediction which might be connected
to treatment with recombinant products.
My opinion is that the biggest factor which
affected the recombinant success rate was the
fact that most patients started at titers that were
greater than ten. If I had to predict that there
was going to be one variable that affected that
group of patients I would have to say that such
a parameter probably did. It’s important to look
at this. We have the opportunity to look at this
in the prospective studies that are going on in
Germany. It is also important to look at all the
PUP data and to look at the true outcome of
immune tolerance with recombinant products.
If we look at some of the data that were presented
by Dr.Lusher and the Refacto data and
the Kogenate data the successes on recombinant
were 45% and 60% which is not very different
from the 55% that I reported. I don’t think
we can get a clear idea about monoclonal unless
we have those data coming from somewhere
else. I just raised it as an interesting issue and I
didn’t wish to make any definitive statements.
MARIANI: I have a comment and a question
for you. Why did you try to analyze the difference
between monoclonal and recombinant I’d
like to know what was behind this decision
because they are very similar in terms of unitage
per milliliter and purity. I don’t think that this
could lead to anything in terms of likelihood of
success. In addition, I would like to point out
that many of the cells in the tables with regard
to your statistical analyses contain are very small
numbers. Therefore I would be very cautious in
drawing any conclusions. People might get confused.
It is probably better not to create many
groups but rather to understand the major differences
unless numbers allow a complete and
detailed statistical analysis.
DI MICHELE: I think your points on the analysis
are well founded. Nevertheless, the reason
we looked at this was because the registry gave
us the opportunity to look at this. The data are
there and to my knowledge they haven’t been
previously examined. You wanted to know if we
will get the answer to that question. As a result
of small overall numbers in the North American
Registry I can’t be sure yet. If you look at it, the
population is small but its sizeable because there
are forty patients in each group and they are
numerically well matched. Therefore, I think that
even though a more detailed analysis is required
I don’t see any reason not to see this as a variable.
LENK: I think in the case of our patients it
would be very difficult to answer this question
because most patients are treated with the same
product. I think it’s quite difficult with relatively
small numbers to give an answer as to whether
a product is better than another product.
CIAVARELLA: I think in America they only use
monoclonal and recombinant products while in
Haematologica vol. 85(supplement to n. 10):October 2000