Friday, 20 March 2015

ClinicSpeak: surviving PML, or not

How many more deaths do we need from PML before we learn the lessons? #MSBlog #MSResearch #ClinicSpeak

"The following publication summarises what happens to natalizumab-treated MSers who develop PML; a quarter of them don't survive and those that do survive are usually left very disabled. The best predictors of a good outcome are young age, less disability prior to PML diagnosis, lower JC viral load in the spinal fluid at diagnosis, and less brain involvement by MRI at the time of diagnosis. The lessons are stark and so are the choices. If you have MS why would you want to take a chance of developing PML with a poor outcome? This point is particularly pertinent now that we have safer alternatives to offer MSers who are on natalizumab and are JCV positive. In those MSers who don't want to de-risk themselves and choose to stay on natalizumab you should be asking your neurology team for 3-4 monthly monitoring MRI scans to pick-up PML earlier. In the MSers in whom PML is detected before it causes symptoms the outcome is usually favourable."

"If you decide to switch from natalizumab to another DMT because you are JCV positive; please be careful about which drug you choose and how you are switched from natalizumab to the next drug. The entity of carry-over PML is no laughing matter. Tragically, as predicted, the first fatal case of PML has occurred in an MSer switched from natalizumab to alemtuzumab without a wash-out or bridge. For more information on de-risking natalizumab treatment please read my post on this issue."


Epub: Dong-Si et al. Predictors of survival and functional outcomes in natalizumab-associated progressive multifocal leukoencephalopathy. J Neurovirol. 2015 Mar 14.

Background: Natalizumab, a highly effective therapy for relapsing-remitting multiple sclerosis, is associated with a risk of progressive multifocal leukoencephalopathy (PML).

Objective: The objective of this analysis was to examine factors predicting survival in a large natalizumab-associated PML global population.

Methods: MSers with natalizumab-associated PML identified through postmarketing surveillance were followed up for up to 24 months using a structured questionnaire completed by treating physicians. Demographic and clinical characteristics, JC viral load, magnetic resonance imaging (MRI) results, and Expanded Disability Status Scale (EDSS) and Karnofsky Performance Scale (KPS) scores were compared in survivors and non-survivors. Kaplan-Meier analysis was used to model survival function.

Results: Among the 336 patients included in this analysis, 76 % survived, with mean follow-up time from PML diagnosis of 16.1 months for survivors; mean time from diagnosis to death was 4.7 months for nonsurvivors. Survivors were significantly younger at diagnosis, had significantly lower EDSS scores and higher KPS scores prior to PML diagnosis, and had significantly lower cerebrospinal fluid JC viral load at the time of diagnosis. MSers with less extensive disease on MRI at diagnosis had a higher survival rate than those with widespread disease. Survivors generally had less functional disability pre-PML, at PML diagnosis, and in subsequent months. In survivors, functional disability appeared to stabilize approximately 6 months post-PML diagnosis.

Conclusion: In this analysis, younger age at diagnosis, less functional disability prior to PML diagnosis, lower JC viral load at diagnosis, and more localized brain involvement by MRI at the time of diagnosis appeared to predict improved survival in natalizumab-associated PML.

CoI: multiple

15 comments:

  1. Does alemtuzumab not carry the same risk?

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    1. Lemtrada causes massive leucopaenia that lasts for quite some time but after the infusion the drug is largely out of the system within a couple of months and means that if there is say an anti-viral cell surviving after the depletion it can re grow and provide immunity against the virus...in contrast the other drugs are constantly present and therefore if the drug blocks the anti-viral response then the anti viral response is blocked and so the risk of PML occurs. The problem with lemtrada is if PML is present and you deplete the anti-viral response and it is gone for some time and so it can be a disaster if you get a rampant viral response.

      I am not yet aware of a PML case on Lemtrada the real risk will be more apparent as more take the rug

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    2. Before my son was treated with alemtuzumab he had a lumbar puncture to test his JCV status. He was being treated off trial so I suppose they wanted a belts and braces approach. Had he been JCV positive he wouldn't have had the drug

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  2. Replies
    1. Thanks an opinion and not shared by every body

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  3. In option 3, deemed "low risk", two oral bridging agents recommended are DMF or Fingolod. Haven't both of these meds been linked with PML on their own? How can they therefore be deemed a low risk bridging agent? What about cycles of anti-inflammatories (Solumedrol) during wash out period instead?

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    1. Yes there have been cases of PMLon tecfidera and gilenya...however the risk is much lower than with tysabri. It appears that the PML is associated with long term depression of white blood cell numbers is white cells

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  4. 1. You say "If you decide to switch from natalizumab to another DMT because you are JCV positive; please be careful about which drug you choose".
    Has there been any studies as to which DMT is best to switch to next?
    2. You say "asking your neurology team for 3-4 monthly monitoring MRI scans to pick-up PML earlier".
    Is this after the 2 year period on natalizumab?
    3. What is the recommended washout period?

    Thanks again for such useful information!

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  5. Has anybody looked at the total picture of risk/benefit with natalizumab? OK, it slows disability by soemthing like 43%?(best case scenario). But that number does not include the patients who die or get considerably worse in a short time because of PML. Neither does it include those patients who after a year or two on natalizumab have to stop the drug because of rising JC antibodies/allergies etc - and get a serious rebound when natalizumab is stopped. ( the EDSS winnings of previous years go rapidly down the drain...)

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    1. the total picture will never be seen,following the death of my daughter no PM requested when PML was strongly suspected. Fatal infection after infusions for four years, the death certificate issued records MS as the cause of death. One fewer case.

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  6. I know there's ALOT of people who when taking alemtuzumab combine it with riuximab, mainly to help combat the cd19 and cd20 cells also? They feel this also helps to lessen the effects of the autoimmune diseases associated with leotards? Is this something you believe too? It also supports your theory regarding ritux and treatment surely?

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    Replies
    1. we need to see the evidence to say whether this is true. If so is this any better than anti-CD20 alone

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  7. Seems like some legitimate questions posed. Love to see a response.

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