Is there any data on disease rebound in patients who switched from Tysabri to Rituximab? Thanks!
Tysabri (natalizumab) is a humanized monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). This disease modifying therapy (DMT) helps reduce the inflammation in the brain and spinal cord, or central nervous system (CNS), that leads to the signs and symptoms of MS. Tysabri has been shown to reduce relapses, the number and extent of lesions seen with neuroimaging in the CNS, and the progression of disability. As with any DMT, individuals will sometimes need to stop Tysabri. In some cases this is because of an increased risk for progressive multifocal leukoencephalopathy (PML), but there are other reasons as well, such as a suboptimal response to Tysabri. However, in a subpopulation of people who discontinue the use of Tysabri, they experience a worsening of symptoms. Disease activity returns to pre-treatment levels or is even worse in some cases, within 3-7 months of the last Tysabri infusion (depending on the study that you read). This is seen as enlarging lesions, increased gadolinium-enhancement on imaging, and exacerbation of symptoms. One explanation provided in the literature is that after discontinuing Tysabri, there is a sort of restoration of cellular immunity and therefore a worsening of neurological deficits. The most severe relapses were seen in those who had the worse inflammatory responses prior to starting the treatment with Tysabri.
This worsening of symptoms, it appears, can happen just from discontinuing the Tysabri, and is independent of drug that follows Tysabri. There are some studies evaluating the effectiveness of other DMT after Tysabri discontinuation. Some who switched to Copaxone (glatiramer acetate) while discontinuing Tysabri experienced as much increase in disease activity as those who did not start another DMT, while in another study, they did not. Switching to Gilenya (fingolimod) from Tysabri also did not prevent the reactivation of MS symptoms.
Their report showed that during the 8 month follow up after switching to Rituximab, there was no worsening of symptoms. However, at this time, there are no long-term safety reports for Rituximab after discontinuation of Tysabri.
This is an area in which research is needed, in order to provide safe strategies for discontinuing the use of Tysabri and preventing disease reactivation.
-Deborah Backus, PT, PhD, FACRM
Director of Multiple Sclerosis Research
The Eula C. and Andrew C. Carlos MS Rehabilitation and Wellness Program at Shephard Center
Q:"I am entering my 8th year with PPMS. What is being done to help and are any comparisons to check with?"
A: Primary progressive MS (PPMS) poses many challenges, not only for the person with this type of MS, but also to the medical and research fields. Although there remain fewer treatments for people with progressive MS, there is a great deal of energy in the research field focused on improving the understanding and care of progressive MS.
In 2012 several organizations joined forces to begin an attack on progressive MS, as the International Progressive MS Collaborative. The MS societies of Canada, Italy, the Netherlands, the UK and the USA, and the Multiple Sclerosis International committed to move forward and became the International Progressive MS Alliance. In 2014, the Progressive MS Alliance developed policies and principles to govern their work, and created a funding mechanism specifically for research in progressive MS. For more information about their work, please see the link http://www.progressivemsalliance.org/. To find out more about the research they are funding, go to http://www.progressivemsalliance.org/research/research-projects-funded-by-the-alliance/
Please also see the entry on 9/19/14 to read a bit more about some other exciting research in people with PPMS... READ MORE
Deborah Backus, PT, PhD, FACRM
Director of Multiple Sclerosis Research
The Eula C. and Andrew C. Carlos MS Rehabilitation and Wellness Program at Shepherd Center
Q: On the neurology congress in Philadelphia in 2014 there was a topic about neuroplasticity and PPMS.
Did they continue to find the influence of neuroplasticity on PPMS patients?
A: There were many exciting findings related to MS research shared at the American Academy of Neurology in May 2014. Of great interest to many were reports specifically related to treatment for people with progressive MS (PMS). Dr. Gary Cutter, Professor of Biostatistics at the University of Alabama, briefly spoke about preliminary findings related to non-pharmacologic therapy for improvements in the arm and hand, as well as legs, in people with PMS.
In this study, Dr. Victor Mark and colleagues examined the effects of a rehabilitation strategy called “constraint-induced movement therapy”. This approach has been studied most extensively in people with paralysis or weakness due to stroke. Constraint-induced therapy involves constraining, or tying down, the less affected arm or leg to force the affected (paralyzed or weak) arm or leg to work for a certain period of time. The idea is that the more affected limb is limited in function in part because the individual has learned to not use that limb, therefore causing it to get worse. In constraint-induced therapy, restricting activity to the more affected limb forces the nervous system to work to restructure itself and restore function in the pathways that cause movement. In other words, by using this approach of forcing the affected limb to work, this is causing neuroplasticity in this system, and hopefully restoring function.
Five people (study participants) with either primary or secondary PMS were treated with constraint-induced therapy with direct supervision of a therapist 3 hours per week for 2 to 10 consecutive weeks (a total of 30 hours of therapy). Study participants performed repetitive tasks that were functionally relevant to them, such as stacking cups or turning items, and tasks were increased in difficulty by the study therapist as the participant demonstrated improvements in performing the tasks. Participants also wore a padded mitt on the constrained limb for a target of 90% of waking hours on training days. The investigators measured arm function before and after the 30 hours of treatment. They also redid the measures 4 weeks after the last therapy session.
Participants demonstrated an improvement in their movement activity log, which measured their real life use of their arm and hand. They also reported a decrease in fatigue with use of their arm and hand.
It is important to note that there were no measures of what was happening in the nervous system. For instance, there were no measures of brain or spinal cord activity before and after the therapy. Thus, it is not clear if changes in function were matched by changes in the nervous system, and due to neuroplasticity.
It is also important to note, and specifically as it relates to this question, that the changes that they saw were still there at 4 weeks post-treatment. However, they were not measured again and it is therefore not clear if the changes last much longer than that. Further study is required to determine how long these changes will persist in people with PMS
Finally, this study had only 5 participants, and a larger study is important to see how much these findings can be generalized to the larger population of people with PMS. However, it is particularly exciting that some people with primary and secondary PMS were able to demonstrate improvements in function. This challenges the traditional dogma that people with moderate to severe MS cannot benefit from rehabilitation.
-Deborah Backus, PT, PhD, Shepherd Center
Mark, V. W., Taub, E., Bashir, K., Uswatte, G., Delgado, A., Bowman, M. H., ... & Cutter, G. R. (2008). Constraint-Induced Movement therapy can improve hemiparetic progressive multiple sclerosis. Preliminary findings. Multiple Sclerosis.
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