Sunday, 26 February 2017

ACTRIMS 2017 further points to Memory B cells

This week ACTRIMS has been going. The academics have been microbioming and even got salt in the act as salt affects gut bacteria, but in terms of pharma news this is a poor companion to ECTRIMS and the AAN.

However, a couple of weeks ago we suggested that drugs that inhibit MS, target memory B cells. 

Have a read (click on the link below)
http://multiple-sclerosis-research.blogspot.com/2017/02/ms-is-b-cell-disease-and-memory-b-cells.html

The data published with dimethyl fumarate was not so great, but it is nice to see data replicated and so more evidence to support the idea comes from ACTRIMS. The effect on B cells was not dependent on whether DMF was associated with leucopaenia and not related to antibody levels. However we know leucopaenia puts you at extra risk from infection.

Dimethyl fumarate effects on circulating B-cell phenotype
Erin E. Longbrake, Claudia Cantoni, Francesca Cignarella, Anne H. Cross MD, & Laura Piccio. ACTRIMS 2017.

Background: The efficacy of anti-CD20 monoclonal antibodies in clinical trials of relapsing multiple sclerosis (MS) confirmed that B-cells play an important role. Little is known about how dimethyl fumarate (DMF) affects B-cells. Objectives: To determine how the composition and function of circulating B-cell populations is affected by exposure to DMF.

Methods: Peripheral blood mononuclear cells (PBMC) and serum were collected from MS patients stably treated with DMF, patients on no immunomodulatory therapy and healthy volunteers. B-cell subpopulations were analyzed by flow cytometry.

Results: The proportions of circulating class-switched memory B-cells (CD20+ IgD- CD27+), non-class-switched memory B-cells (CD20+, IgD+ CD27+) and double negative memory B-cells (CD20+ IgD- CD27-) were significantly decreased among patients taking DMF relative to healthy and untreated MS controls. Concurrently, there was an increase in the proportion of circulating naïve B-cells (CD20+ IgD+ CD27-). Expression of the activation marker CD80 was also reduced on circulating B-cells from DMF-treated patients. Quantitative serum immunoglobulins did not change with DMF treatment.

Conclusions: DMF reduced the expression of circulating memory B-cells. A similar pattern has been observed among other disease modifying therapies, and this may underlie some of the drugs’ efficacy against relapsing MS. More study is needed to determine whether changes in B-cell phenotypic markers are paralleled by changes in B-cell function

15 comments:

  1. Yay! My few months survived on dmf before lymphocyte numbers dropped off a cliff weren't wasted ;-)
    Nice to see indeed.
    MD have you had any luck with Eli Lilly's tabulumab data?

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  2. Hi I tried to get on to the open label ocrelizumab extention trial and was just one day away from meeting the caston doctors when roche shut down recruitment because they met their number targets. Felt dejected. However I have the chance to take alemtuzumab. But given ocrelizumab is still 1 year away from NHS licence if approved Should I risk waiting a year or go for alemtuzumab? My instincts tell me to go all guns blazing before the trickle immune attack becomes a avalanche. Any advice will be most welcome and am sure there are other readers on this blog who have been affected by Roche sudden decision.

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    Replies
    1. Sorry to hear, and yes this happened to patients at BartsMS too. There is a cap by regulators for over-recruitment, and I understand Roche were already close to that, so they had to stop including way more than the planned 600 pwMS into "CASTING" (EudraCT 2015-005597-38). My recommendation would be no to delay treatment. Whether this means the induction/PIRT or escalation pathway using an injectable or oral DMT depends on your specific needs and the health care environment you live in.

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    2. Another way of asking the question is if there will be anything preventing a person who has undergone one or two courses of lemtrada from switching to ocrelizumab when licensed.

      there are 2 parts to that question - one is from a pure medical perspective and the other from the context of NHS.

      :)

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    3. Yes that was my original question. But why would you when one shuts the disease other just stops disease progression. If it weren't for the side effects for some people . Alemtuzumab wins hands down over ocrelizumab. Do you really want to live without your b cells for life?

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    4. "Shutting down" disease may very much depend on impact on B cell subpopulation(s), be it Alemtuzumab or Ocrelizumab. Ocrelizumab seems to work longer than the manufacturer might hope for. I don't see a problem with switching from Alemtuzumab to Ocrelizumab after the first treatment cycle, except that such sequencing hasn't been tested in a trial setting, but that applies to most DMTs.

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    5. Hi Klaus, I live in Berlin and have been lucky enough to get a spot in the CASTING trial. My next appointment will be for the Week48 infusion and MRI. However I'll have to move to London in spring. Could you please tell me who is coordinating the CASTING trial at Barts so I could try to arrange a transfer?

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  3. Ha! Go to the ACTRIMS 2017 forum site http://www.actrims.org/forum2017/. Just a bunch of clinicians having a good old time in the warmth of Orlando, FLA. Maybe a bit of neuro banter as they make the turn on the golf course. Ill bet big pharma is doling out big time in the land of Disney.......aka "the land of make believe" how appropriate.

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    Replies
    1. The USA takes the frugal approach to enticing neuros compared to their European peers that's why there are two different company areas for neuros at joint actrim/ectrims meetings

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  4. This articles talks about RA and memory B cells, maybe a trend?

    http://www.medindia.net/amp/news/cure-for-debilitating-inflammatory-joint-disease-168175-1.htm

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    Replies
    1. They have been using rituximab for some time in RA and so there is much we can learn from this.

      I need to get my head around reports of relapse (in RA) when people are still depleted, whats going on there?

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    2. lol when we mentioned the renewed appetite for b cells in ms to my partner's haemo, he said 'about time' lol. then he said b/t cells are like religion lol. he has a background in immunology.

      in response to our query why is my partner's neuro offering her rituximab re-treatment post hsct when she is doing well, he said that in his view, to give her longevity, if she will have the rituximab, now is better than later - hit them hard before they all come back 'faulty'.

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