Saturday, 14 November 2015

Another Case of PML on Tecfidera/Dimethyl Fumarate without too much Lymphopaenia this time

#MSResearch #MS. Another case of #PML on #Tecfidera #Fumarate

Someone or some people have been criticizing TeamG over what be say, but maybe this person needs to start eating some of their words.

I just posted on the effect of lymphopaenia after DMF and commented on how ProfG disagreed with the EMA advice that a lymphopaenia level of 500 cells per microlitre was OK, when PML had occurred in psoriasis when lymphopaenia had occurred when cell numbers were persistently lower than 800 cell per microlitre.

We then had a spy post two days ago to say that the fourth person with PML and tecfidera had occurred and despite many requests to verify the source nothing was there on the web, so I removed it.

However despite nothing appearing on the Biogen website (why not) sure enough it appears that the fourth case of PML with tecfidera has occurred.

Biogen has apparently reported a fourth case of PML with Tecfidera -- this one in a patient with only moderate lymphopaenia -- to U.S. and European regulators, raising new questions about the drug's safety.

According to Medpage (why is this not easily found on the Biogen website?). The latest case occurred in a 61-year-old female with relapsing-remitting multiple sclerosis, who'd been taking Tecfidera for 22 months before being diagnosed with PML.

She had grade 2 lymphopenia, at 600 cells/mm3, for 6 months before developing symptoms of PML, which included left arm weakness and apraxia. So this comment on Grade 3 lymphopaenia being a limit by ProfG is vindicated it seems.

This is sad news for the person affected and you need to assimilate this if you are a healthcare professional as the EMA guideline needs a rethink.

Apparently Biogen stock has been down-graded recently by Zacks credit rating and it was suggested that if another case of PML occurred it would be bad news..so this bad news may now occur and it is interesting that quite a bit of stock has been flogged in the last day or so...so no chance of insider dealing then?:-)

ProfG is away at present and may say more.

26 comments:

  1. Do you know if she had been on Tysabri prior to Tecfidera? What was her JCV status and antibody index? It would be interesting to know if her index had been monitored.

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    1. Sorry I dont know but would assume they were JC virus positive...surely Bigoen should have all this infomration on their website.

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    2. p.s if biogen send this to me I will post it

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    3. Routine screening for JCV status is currently not required before starting Tecfidera.

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    4. To clarify: JCV positivity must be assumed if there is PML. Ab index is a different matter and probably doesn't play a role anywhere nearly as significant as it does in Tysabri. I'll meet some Biogen staff today, and expect an update on this case.

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  2. Two days ago, Biogen announced another restructuring: https://www.bostonglobe.com/business/2015/11/11/biogen-tricky-transition-from-alzheimer/KSkCNxvxThdMIubVjejcfN/story.html
    This must have been linked to the tecfidera PML case - I guess it was known to the company befre the rumors (now confirmed) started to circulate

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  3. I doubt this person was previously on TYSABRi because if they were Biogen would have used that as the rationale. The fact that they did not mention it explicitly suggests this is not an ex TYsABRI patient and perhaps not even JCV-positive

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    1. You to have JC virus to get PML. Details will surface.

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    2. If an MSer is JCV-negative when starting Tecfidera and have low lymphocytes that could make them vulnerable to getting the JC virus? Is that correct? The virus is very common.

      How often would it be advised an MSer is tested for the JC virus if they are on Tecfidera but the first test was negative? And they have low lymphocytes.

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    3. MD correct me if I am mistaken but risk of PML in JCV- is not 0. So given specific circumstances could someone who ha tears JCV - at some point not get PML.
      Also could that patient who at one pointed tested negative not become JC+ over time, particularly if their titre levels were close to the threshold of conversion? Reading about this a lot and would appreciate additional clarity.

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    4. JCV -ve is only as good as the method of analysis and is a point in time so you can become infected and you can check on the Biogen figures of PML risk in JC -ve it is about 1 in 10,000

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  4. I dont doubt much of anything Prof G says. Been my experience he quite spot on. Is it a surprise? No and yes. No in that he looks at real information and deduces real hypothesis using real logic. Thats what science does.

    Yes, the surprise is he puts it out for people to digest and also cares enough about people to not only put it out there but also enter into the fray of advocacy for people.

    IMHO many a researcher across many a discipline could learn much from his spirit and how to apply that to the passion of their work and research. It would be a much better world.

    We ran an article basically stating people on the med need get regular blood tests done.

    We'd like run an article forwarding people to the PML calculator stuff here but never heard back from anyone? Please email us at msuintes@gmx.com

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  5. Impossible to tell if you're being coy or actually surprised, but Biogen's been concealing the PML risk from the very beginning. Hard to see why they would stop now.

    Massive layoffs at Biogen recently too and they just started adverting Tecfidera on US TV. I'd love to be a fly on that wall right now.

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    1. You maybe right I am still waiting to hear about a PML-associated death that I heard about but can't verify.

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    2. Does Biogen report the post-24 months long term PML outcomes? It's my understanding and experience from surviving the SF AIDS crisis that those stats are not good in AIDS patients and PML-related death jumps after two years post in those with serious complications, so I wouldn't think they'd be great for MSers either. This is a genuine question - I'm negative on Biogen's reporting but I don't have access to what they do report.I saw too many people die of post-PML factors in the 90s which got coded as aspiration pneumonia or similar to think that this is reported correctly in all MS-PML.

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  6. Really sad to hear this. About time Biogen get more rigorous with testing just like they do with Tysabri.
    Do you think this will move Tecfidera to third line?

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    1. No...risk mangement is the sensible way to go

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  7. It's interesting that when there were concerns with the few PML cases found on those who were on the similar psoriasis drug, Fumaderm, Team G had a guest post to quell the concerns prior to the launch of Tecfedera:

    http://multiple-sclerosis-research.blogspot.com/2013/01/guest-post-fumaderm-and-pml-can-we-make.html

    Team G rarely has guest bloggers, but I guess this was needed as an emergency measure to promote the approval of BG-12.

    Now Team G is spinning the situation such that they want more screening. Nice try.

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    1. Do you not think that people with MS will want screening for semi-piece of mind. If I persistently had no lymphocytes then you may be concerned that you are at risk of infection. I am not sure where you are coming from on this one.

      In the USA neuros will be rubbing their hands as another chargable expense comes JC virus check please monitoring of blood counts kerching.

      Rituximab also has had some cases of PML and so they may happen with ocreluzimab.

      As to the last person I asked to do a guest post....they didn't do anything.

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  8. Why are the administrators of this site seem to always be following what is happening to the Biogen stock prices and anyone who questions them must be a Teva rep. It makes you wonder.

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  9. I'd be interested in knowing more about how stable lymphocyte counts usually are in general and how this could impact risk and monitoring. Having recently had 3 blood tests in less than a month, partly for tecfidera monitoring, these have varied every time being 0.9, 0.8 and 1.1. It's a question I'll have for my next clinic appointment.

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    1. Experientia. 1994 Sep 15;50:821-9.
      Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers.
      Maes M, Stevens W, Scharpé S, Bosmans E, De Meyer F, D'Hondt P, Peeters D, Thompson P, Cosyns P, De Clerck L, et al.

      This study has been carried out in order to investigate seasonal variation in peripheral blood immune cells, such as leukocytes, monocytes, neutrophils, lymphocytes, CD3+ T, CD4+ T, CD8+ T, CD25+ T, CD20+ B, and serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R levels in normal volunteers. Toward this end, 26 normal volunteers (13 men, 13 women) had monthly blood samplings during one calendar year for peripheral blood count, flow cytometric enumeration of peripheral leukocyte subsets

      It was found that most of the immune variables change rhythmically during the seasons as a group phenomenon. Statistically significant yearly variations with seasonal rhythms, were found in the number of leukocytes, neutrophils, monocytes, lymphocytes, CD4+ T, CD8+ T, CD25+ T, CD20+ B cells, in the CD4+/CD8+ ratio, It is concluded that the immune system is characterized by a multifrequency time-structure with significant high-amplitude yearly variations in the number of some peripheral blood leukocyte subsets

      Your blood counts vary all the time as they respond to your environment a gut microme a pollen count an true infection your MS etc.

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  10. Will Team G produce an 'Understand your risk of PML with Tecfidera' web app as was done for Tysabri?
    http://www.clinicspeak.com/understanding-pml-risk-on-tysabri/

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