Friday, 13 May 2016

Under starting orders, Rebound of Fingolimod Withdrawal

ProfG recently posted on rebound disease activity after fingolimod 
based on the this paper

Rebound Syndrome in Patients With Multiple Sclerosis After Cessation of Fingolimod Treatment. Hatcher SE, Waubant E, Nourbakhsh B, Crabtree-Hartman E, Graves JS. JAMA Neurol. 2016 May 2. doi: 10.1001/jamaneurol.2016.0826. [Epub ahead of print]

So hot on its heels comes this one

Davion JB, Cambron M, Duhin E, Chouraki A, Lacour A, Labauge P, Carra C, Ayrignac X, Vermersch P. Two cases of relapses in primary progressive multiple sclerosis after fingolimod withdrawal.J Neurol. 2016 May 9. [Epub ahead of print]

We report two cases of primary progressive multiple sclerosis (PPMS) included in the INFORMS cohort, experiencing a relapse related to a single MRI gadolinium-enhancing lesion 3 months after fingolimod withdrawal. These two patients share similarities with relapsing-remitting multiple sclerosis cases described in the same situation, suggesting that the initiating process of the active demyelinating plaques is also present in PPMS, even without relapses, but may be triggered as fingolimod is withdrawn. Although the results of the INFORMS study suggest that fingolimod may not slow down the progression, some PPMS patients might still benefit from a disease-modifying treatment.

Rebound disease activity happens with natalizumab. Here immune cells are trapped in the blood and once natalizumab treatment is stopped they are all lined up ready to go back in the brain. In contrast a depleting treatment may be associated with reactivation of disease but as cells come back slowly then reactivation does not come back with a bang. Fingolimod works effectively like natalizumab and trapps cells in the lymph glands. Stop treatment and they are ready to flow back into the blood and then the brain. So it would be surprising if rebound didn't occur.

In this study rebound relapse occurred in people with progressive MS. This occurred following the end of the trial. Will this figure be higher. About 15% of people with PPMS have active lesions, which should be suppressed by fingolimod so they rebound when fingolimod is stopped.

 I think Novartis want to tell us what the real story is.

14 comments:

  1. This seems to confirm ProfG field hypothesis.
    I really wonder why science don't understand the importance of discover the hidden root cause of this disease.
    Until that don't happens, scientists looks to me like firemen trying to reduce smoking not understanting it is only an effect of fire, and so destined to fail.

    ReplyDelete
    Replies
    1. Pharma is selling products not cures. There is a bit of money funding vit D research in Aus. Other than that who's got the money to look for a cure?

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    2. The vitamin D Trials are sticking plasters if they are being attempted in MS, it simply is not a potent immunosuppressive agent, if it were, people would have many issues with infections. They don't. However how many vitamin D trials are ongoing through the world in a number of conditions. MS I doubt is the best to test the idea and put it to the sword if necessary.

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    3. I would argue there is very little evidence that vitamin d is an immune suppressive agent at all. It is part of the innate immune system, so as the innate immune system comes up to full strength with sufficient supply, the active system has less to do and settles down.

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    4. from what i understood, the vit d testing in Aus is being done on cis as a preventing ms type of thing rather than a cure. in some way it could be a 'cure' for ms, so I included it, otherwise couldn't agree more re the rest of the statements re vit d.

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    5. "The vitamin D Trials are sticking plasters if they are being attempted in MS, it simply is not a potent immunosuppressive agent..."

      This is the crux of the problem. Industry Scientists and pharma are only focused on viable immunosuppressant treatments for a therapy. There is no interest in determining the underlying cause of MS and how vitamin D my act as an immunomodator. There is no profit to be gained.

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    6. Us blogeteers are only interested in effective treatments for MS (and the current immunomodulators are certainly effective, though not without their downsides, our focus on neuroprotective strategies begins to bear fruit) and hopefully a cure. Whether there's any profit in it is of no interest to us and if a cure, from whatever quarter is found, we'll push off and do something else.

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    7. MD2 people can not understand q without scientific basis you can not support a particular approach to treatment. That's what has happened to the topic Vitamin D.

      I personally know a girl who started the DMTs and only with very high doses of D3 every day (it takes 80,000 iu of D3 per day) and guess what? It is outbreak! We have to be realistic, we have MS. I take D3 every day but do not abandon my DMT because I know that there is a scientific basis on which further demonstrates that the D3 alone can replace a DMT, so far it has been shown to help ...

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  2. has the division of MS phenotypes into 4 types really helped people with MS or has it had the effect of withholding treatment from those who may have benefited from it?

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    Replies
    1. Clear it is the latter, a diagnosis of progressive MS has allowed neuros to do nothing as DMT aren't licenced for non relapsing MS. Division of active and non active may be more useful

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    2. thank you for the response - it's taken me almost 12 months (and my partner's diagnosis with each of the four phenotypes with rrms being the final diagnosis) to come to the conclusion that the only thing that matters from treatment point of view is whether her MS is active (it was). you're the 4th person i've asked the question and the first that was brave enough to answer it without ignoring the question and launching into a story of how the 4 phenotypes came to be ;)

      Bojana

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  3. Because the human being in human terms is a very very complex machine far far far more complex than any machine that mankind has ever produced. Trying to understand how that machine works at lowest of levels with all the billions of complex interactions that occur in real time is not only way beyond science's capabilities to do presently... Understanding and correcting what is wrong or goes wrong is even more daunting.

    Even with that we know preventative measures are few.

    For example, in a recent discussion about infectious viruses I put forth that people should be regularly tested for Epstein Barr Virus and variants given diseases that may be associated with it. If a person has EBV and happens to be shedding should they be kissing that 6 month old on the lips no matter who's 6 month or 6 year old that is.

    Who was in the discussion... why the Centers For Disease Control (CDC) here in the USA.

    The response back to this inquiry about raising awareness of this potential issue? ___________ <----- Silence

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    Replies
    1. If you test for something they you need to be able to do something about it, to make it worthwhile.

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