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JCV Jitters

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    JCV Jitters

    Hi,

    I just got off the phone with a Biogen case manager as part of the process for going on Tysabri as a "naive" MSer (first DMT). Here is a question for you experts: I was tested JCV antibody negative on April 10, 2018 which is 3 months ago. If they need to determine continued eligibility for Tysabri every 6 months, aren't I kind of out of whack and should I be having another JCV test before going on Tysabri? My next neuro clinic appointment, when they do tests, is in October. I will also ask Biogen and my provider, but getting an answer from the later is a little more involved.

    All the best, R
    All the best, ~G

    #2
    Hello R,

    Can't you just call and ask your provider? I'm sure they would call back with an answer to such a basic question. Not all clinics follow identical protocols so you should ask where you go. Very likely, if you want an additional JCV assay, they would do it. May I ask when you are supposed to start Tysabri?


    Just a little background on JCV, which as you know can cause PML.


    There was a study of 7724 MS patients which showed that 57.1% tested positive for JCV. I quote part of the study here:


    "Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of JC virus (JCV) infection due to combined host and viral factors. Anti-JCV antibodies provide a means to assess JCV exposure and stratify PML risk. The reported seroprevalence of anti-JCV antibodies varies from 39% to 91% depending on assay methodology and population studied. A two-step anti-JCV antibody assay (STRATIFY JCV; Focus Diagnostics, Cypress, CA, USA) detected anti-JCV antibodies in approximately 55% of multiple sclerosis (MS) patients."

    https://www.ncbi.nlm.nih.gov/pubmed/24894998

    Some pwMS taking Tecfidera, Gilenya, Ocrevus and Tysabri have gotten PML. By far, the greatest number of cases of PML has been seen with Tysabri. However, if you read through the numerous threads here you will discover that no one being infused with Tysabri at 5, 6, 7, or 8 weeks has ever gotten PML. Other threads explain why, and you may want to read them.

    I don't have time right now, I was just leaving but later tonight I will try and post more, if you are interested.

    Oh btw, that variation of 39% to 91% in JCV positivity depends on the population studied and the assay used. For example, if you looked at 10 year old children they might be 30% JCV positive but if you looked at 90 year old adults they might be 90% JCV positive. It is logical that older people get more exposed to JCV or anything else over a lifetime.

    That's why I stick with the 55% figure for the population who is JCV positive. The 7724 MS patients were a spectrum of ages from 10 different countries. Probably best to use that figure here on the MS site.

    Comment


      #3
      Originally posted by Myoak View Post
      Hello R,

      Can't you just call and ask your provider? I'm sure they would call back with an answer to such a basic question. Not all clinics follow identical protocols so you should ask where you go. Very likely, if you want an additional JCV assay, they would do it. May I ask when you are supposed to start Tysabri?
      Thanks for your fast answer, Myoak. Yes it is probably best asked of my provider - which takes a bit of doing. I thought there might be some perspectives here and I truly appreciate the time you took to answer. Based on my reading I don't think it's too urgent to get tested again as long as I am tested in October, but I'll still ask them.

      I did ask about Extended Dosage, and they said no. I think I can negotiate that again in a year or two if I'm still doing well.

      Thank you again, R
      All the best, ~G

      Comment


        #4
        You are welcome!

        Since you are JCV negative and since one cannot get PML unless they are positive, convert to positive, or their test was a false negative, you appear safe getting infusions every 4 weeks. Of course, a second negative test would tend to confirm the first and make the possibility of a false negative even more unlikely.

        PML during the first two years on Tysabri is exceedingly rare whether you are JCV negative or positive, as I am sure you have read. Of course, you want to remain negative which would mean no PML because PML is caused by the JC virus.

        You are absolutely correct that you will be in a position to negotiate EID (Extended Interval Dosing) in the future, so I wouldn't worry about that right now. If you become JCV+ then you could go on EID and de-risk the chance of PML.

        I congratulate you on your choice of Tysabri. IMO, it provides the highest probability of diminishing MS progression short of HSCT.

        If I may make a point which may be of interest relative to PML and the two MS meds, Tysabri and Ocrevus.

        Both Tysabri and Ocrevus target specific B-cells which affect MS. Tysabri blocks these B-cells from crossing the blood-brain barrier. Ocrevus appears to kill certain B-cells.

        Although PML has been seen far, far more often with Tysabri, PML with Ocrevus (and its close relative Rituxan from which Ocrevus was developed) is much more difficult to treat. Before I tell you why please understand that it is possible for a neuro-radiologist, or a good radiologist, to identify PML on an MRI before a person becomes symptomatic if the MRI is done before the patient became symptomatic. That is why it is very important those on Tysabri get timely MRIs. Also, remember, every year you age, your risk of converting from - to + increases slightly; nothing unusual about that.

        PML has no proven effective treatment, yet. However, there is still a better chance of treating PML successfully having been on Tysabri than Ocrevus because Tysabri can be withdrawn and removed by plasma exchange. That does not seem to work as well with Ocrevus or Rituxan. They stay in your system and keep working tamping down immune response, decreasing the B-cells needed to clear JCV. And remember, they have killed off a bunch of B-cells and recovery to restore them can take months.

        There has been some success against PML in Tysabri patients if caught early enough. Anti-malarial drugs have demonstrated some success against JCV, however, much more data is needed. An anti-malarial I am personally excited about is artesunate. There are very good reasons why this could someday be an effective MS DMT but the explanation would require hours and pages.

        Back to the main point....Once Tysabri has been cleared, then B-cells can begin increasing restoring proper immune function against JCV. Remember, over 55% of the population have JCV but in the general population PML is virtually never seen so JCV is not a difficult virus for a proper functioning immune system to thwart under usual circumstances.

        But if an MS DMT acting on B-cells cannot be cleared or reversed efficiently, as is the case with Ocrevus (ocrelizumab) or Rituxan (rituximab) then proper immune function cannot be restored leaving JCV largely unchecked to continue a PML rampage. Sadly, the prognosis in such a case is very poor.

        I hope I haven't been too confusing.

        Temagami, I hope you read this post! I recall you thinking that Ocrevus may not need to be infused every six months. Well, that is pretty darn perceptive of you. 18 months after Ocrevus was halted in trial it was still working just as well as it did when taking it every 6 months. To see the proof, click the link below then click the far right image which is a bar graph. The pdf I downloaded has that bar graph on page 6.

        https://www.ncbi.nlm.nih.gov/pubmed/28161400


        Of course, no treating neurologist on earth would ever show you that graph or even want you to know about it because Ocrevus is FDA approved for every six months and that is what everyone will get, (so far anyway). The reason I put that info here is because I believe people have a right to know everything knowable about a drug they are putting into their body.

        Obviously, one implication is that you could get great coverage against MS using Ocrevus less often than prescribed and perhaps even more importantly, by using it less often with the same effectiveness, (as demonstrated by the study), you may very well decrease the risk of cancer. An increased cancer risk with Ocrevus has not been proven, yet; it does not have a long enough track record. But 2 year trials did show more cases of cancer with Ocrevus than placebo.

        Apologizes for the length. Please note I am not a doctor nor am I giving medical advice. All I am doing is sharing about what I study because it may help someone. I do not have perfect understanding but I do stand by this post. I would not share critically important information if I did not possess a high degree of confidence in my interpretation of it. That will have to do for a disclaimer.

        Comment


          #5
          Your educated posts really do make people feel a lot better about their decisions. Thank you.

          Originally posted by Myoak View Post
          Of course, a second negative test would tend to confirm the first and make the possibility of a false negative even more unlikely.
          This is all the more reason for to ask again before going on the Tysabri, just to have everyone on the team consider it.

          Originally posted by Myoak View Post
          Of course, you want to remain negative which would mean no PML because PML is caused by the JC virus.
          This might be a whole new topic, but I've been wondering about "remaining negative." In terms of causes I did read this: "The high prevalence of JCV in urine and in sewage and the stability of the viral particles observed suggests that contaminated water, food, and fomites could be the vehicles of JCV transmission through the oral route." What other routes are there? Have my days of travel to places with pit toilets and water wells now ended? Perpetual chlorine dioxide water drops? At home, no more cats walking across the pillows? Pasteurized everything? You see where this could go...

          I'm sure you have read about the vaccine for JCV they "started" working on in 2015? Wouldn't that solve a lot of worries?

          Originally posted by Myoak View Post
          Although PML has been seen far, far more often with Tysabri, PML with Ocrevus (and its close relative Rituxan from which Ocrevus was developed) is much more difficult to treat.
          Meaning PML from Tysabri is the best PML! Sorry, we are always seeking a silver lining.

          Originally posted by Myoak View Post
          Remember, over 55% of the population have JCV but in the general population PML is virtually never seen so JCV is not a difficult virus for a proper functioning immune system to thwart under usual circumstances.
          The very general explanation I have retained so far (supported by your post) is that Tysabri prevents the B-Cells from crossing the blood brain barrier. So if everything is status quo except for in the spine and brain, maybe keeping one's immunity as healthy as possible in general could still significantly help to keep those JC antibodies low.

          Thank you again Myoak for all the information you provide and for spurring lots of thinking.

          -R
          All the best, ~G

          Comment


            #6
            Again, you are very welcome.

            And, yes, a vaccine would be wonderful but until then it may be important to understand why the disease course, however rare with Ocrevus (and likely it will remain quite rare with Ocrevus), presents tremendously difficult challenges.

            But no, there is no best PML. PML is a devastating and horrific disease.

            Overall, Ocrevus is one of the very best MS DMTs. While it does have its challenges, PML is unlikely to become one, IMO. However, in rare cases if PML does surface, it will be murderously difficult to successfully resolve for the same reasons which makes Ocrevus a tremendously effective MS med.

            Best!

            Comment

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