Saturday, 18 July 2015

Another case of PML on Tecfidera

Maybe ProfG will comment on this when he gets near cyberspace and not doubt Biogen have circulated this information, around the neuros. But based on info on the web there has been another case of PML on somebody using tecfidera. Based on the scant information on the web.

This was a PPMSer who was severely leucopaenic. So immunosuppression can in some people cause white cells counts to go very low and as you keep taking the immunosuppressive your white cell numbers are not going to recover. If that happens you are going to be at risk from infection. This is biology and this is where induction therapy has an advantage as you are not on rug all the time and once the drug has washed out your white cells can recover if an infection comes along. 

I am aware that BG00012 and Disability Progression in Secondary Progressive Multiple Sclerosis (SPMS) (INSPIRE) is recruiting but there is no evidence that Tecfidera is useful for people with PPMS.

There has been spin that BG-12 was going to be neuroprotective, but the drug was not universally effective in atrophy measures and the question of CNS penetration has not been clarified. 

It shows us that drugs come with risk profiles and this problem may have been avoided by a risk-averse neuro,who would not prescribed off-label. 

However, there may have been gadolinium lesions in the PPMS case.

9 comments:

  1. PML risk should be assessed person to person, statistics means very little when you're the one left holding the short straw.

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  2. Exactly. When people talk about risks I think well my chance of getting MS was 1000 to 1 but I was the one person that got it.

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    1. Oh, I think the odds are much higher than 1000 to 1. But I do agree that there needs to be more individual assessment, and this does seem to be happening to some extent with PML in UK, well at my hospital at least.. I'm JC positive but with an very low titre so my odds for first two-years are 'apparently' the same as a JC negative person. I don't intend to stay on Ty for any longer than that anyway.

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  3. I feel the same. As a man the odds of getting MS are more like 1:1500. Someone didn't like me. If I take a treatment and then get the low probability bad side effects, someone really didn't like me. However, not taking any treatment is the worst risk of all - disability pretty much guaranteed.

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  4. leukopenia has been the central issue with the recent cases of PML and suggests that monitoring is in order..

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  5. I'm on Tecfidera and JC positive. I've been reading about leukopenia and some of it's causes. These include anemia or a vitamin deficiency. Deficiency in minerals.
    Highlights the importance of a healthy well balanced diet. Sleep is important and recommended 7 to 8 hours a night can help improve white cell count.
    I'm just thinking of what might help me lower my chances of getting leukopenia.

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  6. Sooner or later, we'll be doing systematic risk partitioning like with Tysabri. I found this informative: https://www.reddit.com/r/MultipleSclerosis/comments/3af5jx/tecfidera_lymphopenia_jc_virus_and_how_do_you/

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  7. Should cd4/cd8 ratio be added to tecfidera monitoring?
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335821/

    Last paragraph -
    Currently, the manufacturer recommends that lymphocyte counts be monitored every 6–12 months on DMF therapy and that interruption be considered when lymphocyte counts decrease below 500 cells/μL and remain below that level for more than 6 months. We have observed that CD8+ T lymphocyte counts fell below the LLN in some patients at 12 months of DMF treatment, even though total lymphocyte counts were greater than 500 cells/μL. Monitoring T lymphocyte subsets during DMF treatment of MS may be beneficial.

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    1. ProfG may care to comment,but I think I asked him this question yesterday. At the moment they are just do total white blood cells count but my guess that in future this may change, especially if immune cell phenotypes can be shown to be important.. Maybe leucopenia of B cell subsets to show efficacy and T cell subsets for PML risk

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