Natalizumab-associated PML Risk: June 2012 Update

N



IS = previous exposure to immunosuppressive drugs


“There have now been over 210,000 patient years of exposure. As of the 6th June 2012 there are 258 confirmed cases of natalizumab-associated cases of PML. The risks are beginning clearer with time, as noted by the decreasing size of the error bars in the figure above. The smaller the error bars the more certain the estimate.”


“Do you find this information helpful? Should we keep updating you?”


CoI: multiple, these data have been provided by Biogen-Idec

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

19 comments

  • And the high risk category is showing higher risk it was 1 in 94 a the beginning of the year this has dropped to 1 in 90.

    If JC negative has gone from 1 in 10,000 to 1 in 11,000.

    May sure you know your JC virus status

  • All of our tysabrias are tested for JCV so yes you should do this is you are considering tysabri as it it helps inform your descisions

  • this information is very valuable to us. my girlfriend uses TYSABRI and she is positive JC. Why 1 in 1786 get PML? Is there a more dangerous virus in some patients? I have heard that in some hospitals look at the virus level, assigning a risk level of 1, 2, 3 as a function of the amount of virus. more virus-more risk. Is this true?my girlfriend has oligoclonal IgM bands anti phosphatidylcholine (agressive rrms). his neurologist told us that patients with IgM have an immune system more powerful and they are more protected against PML. They will publish it this year and this will be another element in the risk stratification of PML, likely. is this true?what is the best option after Tysabri to prevent rebound of disease activity? in our hospital they use 6 months on copaxone and after, gilenya. have vitamin D levels above 100 can prevent the rebound? REGARDS, ALVARO

  • Re: "Is there a more dangerous virus in some patients?"

    Yes, it is a mutant virus that causes the PML. We have been able to detect or monitor the mutant in MSers on Natalizumab.

    "I have heard that in some hospitals look at the virus level, assigning a risk level of 1, 2, 3 as a function of the amount of virus."

    No sure about this. There is some theoretical data that suggest if your titre of antibodies against the virus go sup this increases your risk. Not enough numbers to confirm of refute this.

    "My girlfriend has oligoclonal IgM bands anti phosphatidylcholine (agressive rrms)."

    This has been reported as being a poor prognostic sign in some MSers. It needs to be confirmed. I am unaware of it being linked to an increase in PML risk.

    "What is the best option after Tysabri to prevent rebound of disease activity?"

    Depends on what the MSer has been on before. If no exposure to IFNbeta or GA, it is worth trying those. If these have failed then fingolimod. Other orals are on the way therefore more choice.

    Re: "In our hospital they use 6 months on copaxone and after, gilenya. have vitamin D levels above 100 can prevent the rebound?"

    No bad advice; it is opinion and not based on evidence. I agree a 6 month wash out would be long enough to prevent carry-over PML risk.

  • Gavin thank you very much for your reply. now, is it possible to detect if a patient has the virus that causes PML? my English is very bad. I did not say that igM increases the risk of PML. is the opposite. IgM is protective against PML. this year, neurologists in our hospital will publish studies about this. then, is it good idea to have vitamin D levels above 100 to try to prevent post natalizumab rebound? Any other recommendation? What is the date of marketing of BG12? thanks, alvaro

  • Re: "is it good idea to have vitamin D levels above 100 to try to prevent post natalizumab rebound? Any other recommendation?"

    It is a good idea to have your vD level above 100 for many reasons. There is no evidence that this will stop or reduce MS disease-activity post natalizumab. In fact that evidence that vD is a DMT is very weak hence the need for larger studies.

    "What is the date of marketing of BG12?"

    The EMA are assessing it now; if all goes well we are expecting it to be available next year. Access to the drug will depend on its license and cost.

  • 264/58 (PML/deaths) as of Jyly 3rd. Maybe Tysabri should not be given anymore to JC seropositive patients with prior IS use. The risk has climbed too high.

  • The risk is about the same as last month but is a risk and that is why we post so that you can weigh up this risk verses the benefit.

    But agree with you that we need to get another treatment that does not have this PML risk

  • What is the date of marketing of BG12?"

    It depends on the regulators but maybe any Biogen readers cn fill us in

  • Re: "The risk has climbed too high."

    Please try and not make decisions for other MSers. It may be too high for you! There are some MSers, who had very active malignant MS, who are now stable on Natalizumab who may think this risk is worth taking. I have stressed on this blog over and over again it is not the regulators or healthcarers who should prejudge what risks are worth taking but the people with the disease.

    You must also remember that the risk only increases after 12 months and in particular 18-24 months. Therefore Natalizumab may be suitable as a holding therapy until new DMTs emerge.

    No clinical decision is straightforward any more, which is why we talk about personalised healthcare.

  • Hi earlier there was a question Re: "Is there a more dangerous virus in some patients?"

    and answer

    Yes, it is a mutant virus that causes the PML. We have been able to detect or monitor the mutant in MSers on Natalizumab.

    "I have heard that in some hospitals look at the virus level, assigning a risk level of 1, 2, 3 as a function of the amount of virus."

    No sure about this. There is some theoretical data that suggest if your titre of antibodies against the virus go sup this increases your risk. Not enough numbers to confirm of refute this.
    my question is ….. I wonder if you could provide any more info on possibility of finding out if one has the mutant virus in order to have better idea of ones risk in starting on this drug thanking you ..Robyn

    • Robyn,

      Re: ""I have heard that in some hospitals look at the virus level, assigning a risk level of 1, 2, 3 as a function of the amount of virus."

      This is not evidence-based at present. There is a rationale behind using the titre to assess risk, but all the data we have at present looks at sero-negative vs. sero-positive subjects. The rationale is as follows; if you have early PML the virus that is being produced within the brain is boosting the immune system in the periphery to increase the amount of anti-JCV antibody. Therefore a rise in titre or levels of antibody to the JC virus may indicate that it is multiplying out of control within the CNS.

  • Hi earlier there was the question Re: "Is there a more dangerous virus in some patients?"
    And the answer

    Yes, it is a mutant virus that causes the PML. We have been able to detect or monitor the mutant in MSers on Natalizumab.

    "I have heard that in some hospitals look at the virus level, assigning a risk level of 1, 2, 3 as a function of the amount of virus."

    No sure about this. There is some theoretical data that suggest if your titre of antibodies against the virus go sup this increases your risk. Not enough numbers to confirm of refute this.
    My question is
    …..I wonder if you could provide any more info on possibility of finding out if one has the mutant virus if you are able to monitor the patients with the mutant virus or any other test in clinical use to help patients further determine their risk profile if they are JC positive eg a test to show the amount of antibosies or a test to show if they have the mutant virus

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