Rituximab in the switch from natalizumab.

Asztely F, Gilland E, Wattjes MP, Lycke J.
J Neurol Sci. 2015;353(1-2):155-7.

multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) after 43 months of natalizumab treatment. New clinical and magnetic resonance imaging (MRI) findings were initially misinterpreted as breakthrough MS disease activity and natalizumab treatment was replaced by rituximab treatment. The patient had a single infusion of rituximab 1000 mg before a definite PML diagnosis was confirmed. Despite undetectable levels of B-cells, JC virus DNA became undetectable in the cerebrospinal fluid by quantitative polymerase chain reaction. The patient partially recovered without any clinical or MRI signs of new MS activity. These findings suggest that B-cell depletion in a non-immune compromised individual did not prevent the patient from clearing the JC virus infection.

PML is the ticking time bomb that anyone on a DMT will be worried about if you are JC virus positive, which 50% of pwMS are. So if you are talking natalizumab and have been on drug for over two years, you may be switched. If you wait too long between withdrawing drug you may get disease reactivation of MS, and if you have a sub clinical viral infection, once the cells have escaped the control by natalizumab then they can enter the brain and this is called IRIS. Immune reconstituion inflammatory syndrome. However what do you switch to, I have heard of people have been switched to alemtuzumab, but as a marked T and B cell depleter it can be disaster and some one may have died due to uncontrolled JC virus in the brain PML. In this case the JC virus infection was foud after infusion and the B cells were gone….at least for 6 months based on studies in other people. But the virus was cleared perhaps indicating that the virus is cleared by T cells, probably CD8 T cells, so is ritiximab going to be a drug of choice is the switch or will ocrelizimab take its spot. I suspect it may take a few spots.

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  • I suspect MD means that there will be multiple use cases for Ocrelizumab. I think that Ocrelizumab may become the standard treatment for MS. A treatment of two infusions a year that is effective with a good risk profile.

    • Especially when it looks like it is an induction therapy.

      So who is not publishing te phase II extension data. Shame the neuros involvex spoke to the media and left the results in the public domain

    • "Especially when it looks like it is an induction therapy."

      Is there evidence for this? Which comments to the media are you referring to?

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