Wednesday, 6 August 2014

ClinicSpeak: plasma exchange to remove natalizumab as a treatment for PML

Are you at risk of PML? This post is for you. #ClinicSpeak #MSResearch #MSBlog

"The following case series describes the number of plasma exchange (PLEX) procedures needed to remove natalizumab from the blood varies and depends on the level of natalizumab in the blood. The more natalizumab in the blood the more PLEX sessions. This is important because if you develop PML as a complication of natalizumab treatment you need to reconstitute immune surveillance to clear the virus from the brain. There are two options; you can either wait 3-4 months for the natalizumab to clear spontaneously, or you can wash-out the natalizumab over 5-10 days with PLEX. The problem is that when the immune surveillance is restored and the T-cells that are necessary to clear the JC virus enter the brain they cause an encephalitis; we refer to this as IRIS (immune reconstitution inflammatory syndrome). IRIS in itself can be very dangerous, particularly if the PML is extensive and/or it involves the brainstem, an area of the brain that houses vital structures for keeping you alive. To prevent severe IRIS we often recommend using steroids."

"The downside of washing-out natalizumab is that it also allows MS to reactivate, so called rebound, and hence something needs to be done about this. DMTs that suppress the immune system are a no-no as the immune system is required to fight the PML, hence the only drugs possible in this situation are immunomodulators; IFNbeta, GA and possibly DMF. I say possibly DMF as it is probably not an immunosuppressive drug, unless it causes a very low lymphocyte count, which happens rarely. The important thing about natalizumab and PML is that it does not have to occur. Those at high-risk should really come of the drug, or at least go onto regular 3-monthly MRI monitoring so that PML can be detected early, in the asymptomatic phase, and treated early. The outcome of PML when it is detected early, before it causes symptoms, is so much better (see slide 35 & 36 in the deck below."

"I still have sleepless nights over natalizumab and PML.  Despite advising all our high-risk patients to come off the drug a few patients want to stay on the drug. These are typically patients who have had very bad MS and are now doing very well on natalizumab. I keep telling the MS Team that it is simply a numbers game and it is only a matter of time before we have our first case of PML at the Royal London Hospital. I fear that day!"


Background: Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab treatment. Restoring immune function by plasmapheresis/immunoadsorption (PLEX/IA) is important for the outcome of PML. 

Cases studies: We report on four MSers whom developed PML during natalizumab treatment, in whom we measured serum natalizumab concentrations before and during PLEX. Depending on the serum natalizumab concentration at the time of PML diagnosis, the number of PLEX treatments necessary to reach subtherapeutic serum natalizumab concentrations is variable. 

Conclusions: Measuring serum natalizumab concentrations before and during PLEX is helpful to determine the optimum number of PLEX treatments in individual MS patients with PML.

CoI: multiple

4 comments:

  1. Why not switching those patients to Campath?

    Same reward (or perhaps better) for less risk (no risk of death at least)

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  2. With so much data collected for Tysabri patients, it's hard to believe there has not been a single mitigation strategy proposed.

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  3. I'm on Tysabri drug trial and looking at following on to actual treatment and am JC positive. This is scary but so is SPMS.

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    Replies
    1. How about the point I raised above?

      In principle, I am bewildered by high-titred JCV+ patients who stay on Tysabri without considering Campath.

      It seems as a no-brainer to me....

      Delete

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