Friday, 1 November 2013

Brain atrophy rates on DMTs

Brain atrophy rates on DMTs #MSBlog #MSResearch

"This post is in response to a request from one of our readers and is a quick and hasty post from multiple sources on my hard drive. Unfortunately, I don't have brain atrophy data for teriflunomide. I don't think the data has been presented at a meeting yet and is therefore not in the public domain. Although I know what teriflunomide does to brain atrophy I am not in a position to disclose the data as I am under a NDA, or non-disclosure agreement, with Genzyme." 

"Brain atrophy is a very important issue in MS; it is present from the outset of the disease, occurs in all stages of the disease and correlates with poor outcome. Reducing the rate of brain atrophy is becoming an important attribute of DMTs. Drugs that slow the rate of brain atrophy are more likely to address the neurodegenerative processes in MS that are responsible for disease progression."
"It is difficult to compare drugs in relation to brain atrophy as the biology of different classes of treatments is different. What we do know is that drugs that are predominantly anti-inflammatory tend to shrink the brain in the first 6 to 12 months of treatment. This is called pseudo-atrophy and occurs as the swelling of the brain due to inflammation resolves. These drugs tend to slow atrophy in the second and subsequent years. In comparison fingolimod and laquinimod that have additional effects on the so called glial cells start to have an effect on slowing brain atrophy within the first 6-12 months. Whether or not the early effect of fingolimod and laquinimod on brain atrophy is due to early neuroprotection, or due to a change in cell volume, is a moot point at present. Despite both  these drugs have interesting modes of action and need to be explored further, particularly in progressive MS."

Older or established DMTs



Emerging DMTs

BG12 or Dimethyl Fumarate (ECTRIMS 2012)


Alemtuzumab (ECTRIMS 2013)


Laquinimod (ECTRIMS 2012)


Daclizumab (ECTRIMS 2013)


Other posts of interest on brain atrophy:
Multiple Sclerosis Research: Survey results: brain atrophy in MS
28 May 2013
The only way we are going to get brain atrophy up the agenda is for you to ask your neurologist about whether or not you have evidence of brain atrophy on your MRI. Unless the atrophy is gross atrophy, i.e. visible to the ...
http://multiple-sclerosis-research.blogspot.de/

Multiple Sclerosis Research: Brain atrophy: what to do about it?
31 Jan 2013
"I was asked by a colleague in Porto last week whether or not I let the presence or absence of brain atrophy on MRI affect my clinical decision making about DMTs and treatment? I had to think about the question and haven't ...
http://multiple-sclerosis-research.blogspot.com/

Multiple Sclerosis Research: Version 4 of ECTRIMS brain atrophy ...
30 Sep 2013
Version 4 brain atrophy infographic; comments please. #MSBlog #MSResearch "The following is version 4 of my brain volume infographic that I will be using at the blogging session at ECTRIMS. I still have time for changes.
http://multiple-sclerosis-research.blogspot.com/

Rebranding MS a dementia (7): disease progression and brain ...
05 Jul 2013
Rebranding MS a dementia (7): disease progression and brain atrophy. Progressive brain atrophy; should you accept it? #MSBlog #MSResearch. Epub: Hofstetter et al. Progression in disability and regional grey matter ...
http://multiple-sclerosis-research.blogspot.com/

7 comments:

  1. Prof G,

    Thanks for this. For the patient it's a bit like working out the best energy tariff from the various suppliers. None of the drugs mentioned above appear to really impact on brain atrophy i.e. 95 per cent reduction (believe me you'd want that efficacy if you had MS). Are there are other treatments in the pipeline which might get closer to really reducing brain atrophy. Thanks.

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    1. Unfortunately, you will never stop brain atrophy as it is a normal phenomenon. As an adult over the age of ~35 you lose between 0.1-0,4% of you brain volume per year. MSers lose brain volume at rate of ~0.8% per year; essentially double the normal rate. Until we include an age-matched control group in the trials we won't know if any of these drugs normalises brain atrophy rates.

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  2. On Aubagio I found this info:
    " No significant differences in
    brain atrophy from baseline were observed among the three groups."

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673963/

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  3. Why can't we see brain atrophy data on BG-12 for the complete study group? What is presented seems to be just a sub-group. It that really good science/reliable? I am not accusing you of anything, but I suppose BIOGEN Idec has the complete data? The data for Fingolimod and Laquinimod seems to be based on the complete study group, and is for that reason more reliable ( no post hoc data-mining.. )

    Any theory why the TID is worse than BID?

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    Replies
    1. To save money Biogen-Idec only did MRI studies on a subgroup of MSers. This makes sense as MRI studies are expensive and more sensitive than clinical outcomes therefore you need fewer scans to show a significant difference. I think this approach is smart; some would argue it is unethical to do more investigations than is necessary to get an answer.

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    2. TID is not worse than BID; the difference is within the statistical error rate or noise. There is no difference between the two doses.

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  4. There is a Credit Suisse note out today saying "Laquinimod the Best NIMO Via Brain Atrophy?". They compare data and find that among the NIMO's Laquinimod is #1. The final words are " things sometimes unexpectedly change. "... Maybe it was not expected that focus would shift from relapses to something else?

    CSB's definition of NIMO includes Aubagio, Tecfidera and Laquinimod. Gilenya is an immunosuppressor.

    CSB seems to have same view as you guys on treatment of the MS-disease:

    " We reiterate our view that the clinical management of MS is changing from a “treat-and-see" to a "treat-to-goal" disease. "

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