Friday, 9 June 2017

CD20 Depletion works in MS

Xie Q, Li X, Sun J, Yuan B, Li Y, Wang L, Wang M.A meta-analysis to determine the efficacy and tolerability of anti-B-cell monoclonal antibodies inmultiple sclerosis. Exp Ther Med. 2017;13(6):3061-3066.

The present study performed a meta-analysis of randomized controlled trials in multiple sclerosis (MS) patients to evaluate the efficacy and safety of anti-B-cell monoclonal antibodies (mAbs). To the best of our knowledge, no previous meta-analysis has evaluated this. Relevant studies published until March 2015 were retrieved from the PubMed, EMBASE and Cochrane Library using the following keywords: 'Clinical trial', 'randomized', 'multiple sclerosis' or 'MS' and 'monoclonal antibodies' or 'mAbs'. Two authors independently selected the articles and extracted the data. The meta-analysis was performed using Review Manager version 5.3 software. Four randomized clinical trials comprising a total of 745 patients were selected. Anti-B-cell mAb treatment reduced the formation of gadolinium-enhancing lesions [mean difference (MD)=-5.62; 95% confidence interval (CI)=-8.00 to -3.24; P<0.001) and was associated with smaller volume changes of lesions on T2-weighted magnetic resonance imaging (MD=-604.40; 95% CI=-941.23 to -267.57; P<0.001). It also significantly reduced the proportion of MS patients having at least one relapse [odds ratio (OR)=0.25; 95% CI=0.14-0.44; P<0.001). Compared to placebo, anti-B-cell mAb treatment did not increase the frequency of adverse events (OR=0.90; 95% CI=0.54-1.49; P=0.68) and serious adverse events (OR=1.13; 95% CI=0.70-1.80; P=0.62). In conclusion, the present meta-analysis suggested that anti-B-cell mAbs are a relatively effective and safe treatment for MS.

So here we have a meta analysis up to 2015 and it says CD20 B cell depletion works in MS, which is not surprising as in 2017 there were two phase III studies in MS and they said anti-CD20 depleting antibodies work in MS.  Phase III trial verse meta analysis..no contest.

There were no serious adverse events in this meta analysis, and likewise in the trials the depletion was well tolerated but it is a numbers game and eventually some people will have some serious infections if we do not watch-out. This was a reason whilst development of ocreliziumab was terminated in arthritis and Lupus.

What we want to know is does it deplete memory B cells?
How long does it deplete memory  B cells for?
Does it have to be given every 6 months or is it a induction therapy also?
Does it have a cancer (breast cancer) risk, etc, etc?
Will it get approved by the EMA? etc, etc etc
  

4 comments:

  1. can you please discuss more opportunistic infections and ocrelizumab?

    ReplyDelete
    Replies
    1. The data we have access to is in the clinical trial reports which are open access

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  2. That study is mainly RRms patients?
    In this other from PPms there as no real efficacy

    http://multiple-sclerosis-research.blogspot.com/2016/04/researchspeak-failure-of-intrathecal.html

    This other has agressive ms ,would´nt this be an ideal candidate to do hsct?

    http://multiple-sclerosis-research.blogspot.com/2017/04/aan2017-b-cells-remain-in-brain-after.html

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  3. When it comes to B-cell-depletion (or T- and B-cell depletion as with alemtuzumab) following treatment with Fingolimod:
    How long should you wait till starting treatment with i.e. ocrelizumab/rituximab to be sure, that the lymphocytes do not hide in the lymph nodes....?
    Is 6 weeks enough if the blood count shows a normal lymphocyte count, or how do you make it?

    ReplyDelete

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