New Clinical Trials for Rituximab, Alemtuzumab, Daclizumab

Dr. Kantor Health Guide
  • The American Academy of Neurology had its annual meeting recently, where the newest in research is presented with the hope of better treatments. At this year's meeting, we heard a lot about updates of clinical trials we are all becoming familiar with:

    1. Rituximab - the monoclonal antibody directed against B cells. You will remember that antibodies are the immune pieces which bind to other substances in the body. Monoclonal just means that they are all exactly the same - mono like one; clonal like copies (all the copies are the same). In MS we talk about T cells a lot, but we are learning that B cells are important too. B cells make antibodies against infections and other foreign invaders, and it looks like they are important in the body fighting itself in MS (autoimmunity).

    Rituximab is being tested in relapsing-remitting MS (RRMS) and the longer term data was presented, showing that it reduces relapses and MRI activity (there was actually an article in the New England Journal of Medicine about this in March, which many of you received as a research alert from the NMSS).

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    Rituximab was also being tested in primary-progressive MS (PPMS), but unfortunately it was a negative trial. This does not mean that it does not necessarily work for people with PPMS, but it does mean that the company who makes it will not look into this avenue further and that the FDA will obviously not approve it for PPMS.

    1. Alemtuzumab - the monoclonal antibody directed against cells which carry the marker CD52. CD52 is present on lots of types of immune cells, including T cells, B cells and monocytes (the most common infiltrating immune cells in the central nervous system). What is interesting about Alemtuzumab is that it is given for several days once a year (in the studies it was 5 days, IV, one year and then 3 days the next year). This would be exciting since it would give everyone a break for the other 360 days of the year. Alemtuzumab pushes down the T cells, B cells and monocytes. While the T cells stay low for a long time, the B cells and monocytes start rising after 3 months and even get higher than they started. Don't forget that Rituximab is an anti-B cell medication and now we are talking about a medication which makes B cells higher!

    We definitely need to figure out why they would both work in the same disease process and if there are long term consequences of this.  The most amazing thing about Alemtuzumab is that it beat Rebif® (interferon beta-1a under the skin, three times a week) by 75%! This is an exciting new avenue for MS treatments but it will be many years before we see it come to market (if it does).

    1. Daclizumab - the monoclonal antibody directed against the IL-2 Receptor alpha chain. You will remember that last year there was a paper about the genetics of MS and how some people have involvement of the IL-2 Receptor. This may be why this medication works, because it blocks a certain part of the IL-2 Receptor, which sits on the immune cells. What was disappointing about the results released this year for this subcutaneous medication (under the skin), is that once you stop the medication, the MS activity comes back. This is not surprising, since it is true of the medicines that people with MS use nowadays, but it is different than the exciting results with the other monoclonal antibodies.

    This is all very exciting, but there are a couple of issues to remember:

    1. It will still be a few years before these medications are ready for prime time.
    2. All of these newer medicine carry more risks and potential side effects than the medicines we are using nowadays. Now this may be worth it, if a medicine is a lot stronger, or a lot more convenient, or you can't tolerate the older medicines. This is why it is so important to work closely with your neurologist, in order to direct your own care.

    Remember, the Multiple Sclerosis Team Approach Tule (M*STAR) places the patient at the center of the MS team. Once you are firmly directing your own team, it is important to reach out to help other through the Multiple Sclerosis Patient Network (M*S*P*N): mstar.mspan@gmail.com

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    So, with these more risky medications, how is MS care going to look in the future?

    We need to work towards individualized treatment, and this is going to come with genomics and proteinomics - basically seeing how individuals respond to therapy. First, however we need to collect this genetic data. A great way to do that is if you are:

    • African American

    or

    • Caucasian American with both parents alive

    Then there is a blood study (this is not an experimental treatment trial) that you could be a part of to help the global knowledge base. If you are interested, call Yasmeen at (904)244-9814.

     

Published On: April 30, 2008