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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption. Tolle, Scheibenbogen et al. 2020

Discussion in 'ME/CFS research' started by John Mac, Jul 30, 2020.

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  1. John Mac

    John Mac Senior Member (Voting Rights)

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    https://www.mdpi.com/2077-0383/9/8/2443
     
    John Mac, Jul 30, 2020
    #1
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  2. Legend

    Legend Established Member (Voting Rights)

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    I'm sorry to ask. But what is a modified IA protocol?
     
    Legend, Jul 30, 2020
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  3. Trish

    Trish Moderator Staff Member

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    In the full paper they explain: 'Patients who had responded to the first IA (IA1) were retreated with a modified IA protocol (IA2) about two years later. Here, IA cycles were given with longer intervals.'
    So the immunoadsorption was done on days 1, 2, 3, 6, 7 on the first version, and days 1, 2, 4, 6, 8 on the modified version.
     
    Trish, Jul 30, 2020
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  4. hinterland

    hinterland Senior Member (Voting Rights)

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    IA = Immunoadsorption.

    From Wikipedia:
     
    hinterland, Jul 30, 2020
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  5. butter.

    butter. Senior Member (Voting Rights)

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    looks placeboish
     
    butter., Jul 30, 2020
    #5
  6. John Mac

    John Mac Senior Member (Voting Rights)

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    A placebo controlled trial should answer that. The researchers suggest that.
    Just because there is a fall in a biological measurement doesn't mean that it is the cause of the symptom improvement, it could easily just be placebo.
     
    John Mac, Jul 30, 2020
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  7. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    An 80-90% decline in total IgG sounds seriously bad news to me. We used to worry if there was a 50% reduction with rituximab. Unless there is some good reason why this is considered acceptable, perhaps in the short term, I would not recommend continuing to study this protocol.
     
    Jonathan Edwards, Jul 30, 2020
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  8. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    You mean they would be very vulnerable to contracting/dying from an infection with that much IgG depletion?
     
    Last edited: Jul 30, 2020
    Jaybee00, Jul 30, 2020
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  9. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    They are removing them from the plasma only so it's a bit different to Rituximab I believe. How quickly do they come back? By the way, Fig 3 shows the values for all patients normalised to 1 at the start. I think the square data points are total values.
    Full text PDF : https://www.mdpi.com/2077-0383/9/8/2443/pdf
     
    wigglethemouse, Jul 30, 2020
    #9
  10. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    The point is that they might be. Resistance to infection is complicated and some people manage on low IgG levels but an 80-90% reduction puts someone into seriously risky territory.
     
    Jonathan Edwards, Jul 30, 2020
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  11. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Plasma is the only relevant compartment for antibodies so it is the same as for rituximab. They are not affecting B cells but the relevance of affecting B cells is only through the knock on effect on plasma antibodies in both situations.
     
    Jonathan Edwards, Jul 30, 2020
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  12. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I have only had a quick look at the paper but it seems only to give us IgG and antibody levels for 9 days. This is completely meaningless from my perspective since to be any use one would want antibodies to go down for months at least.

    (The paper is published in something I have never heard of called Journal of Clinical Medicine, which sounds to me like one of the new journals that will publish anything. Peer review should have insisted on longer term Ig levels - that is if I am right that these are not given.)

    The key point is that treatment aimed at reducing antibody levels is only a reasonable idea if there is some specificity that lasts over months. Rituximab is useful because for reasons we do not fully understand there is very useful specificity. It does not look as if there is any here.
     
    Jonathan Edwards, Jul 30, 2020
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  13. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    Okay, lost in the mass of text was a statement that they replaced IgG after IA. The focus was on removing damaging antibodies and partially replacing the good ones. However, I thought IgG infusions had a half life of 21 days......
     
    wigglethemouse, Jul 30, 2020
    #13
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  14. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    They say that IA reduced memory B cells as well
    I'm not sure what they mean by frequency........... maybe lost in translation?
     
    wigglethemouse, Jul 31, 2020
    #14
  15. Hutan

    Hutan Moderator Staff Member

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    Participant selection
    The 5 participants were regarded as responders to a previous trial of the therapy (IA1 in 2018). And all of the participants had increased B2AR-ABs. So, this is not a random sample. That's ok, but something to keep in mind.

    Treatment
    The treatment in IA1-2018 was 5 IA in 7 days, with assessment on day 8. Worsening fatigue but improvements in other symptoms doesn't sound that good - I think it would be difficult to assess improvement.

    The IA2-2020 treatment schedule was 5 IA in 8 days, with assessment on day 9, with a lower dose of replacement IgG after the final IA session.

    Assessment
    The followup was done for 12 months.
     
    Last edited: Sep 3, 2023
    Hutan, Sep 3, 2023
    #15
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  16. Hutan

    Hutan Moderator Staff Member

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    Results
    Levels of IgG and of autoantibodies decreased during the treatment period.

    Regarding IA1- 2018 and the long lasting improvements - only some of the ten patients seemed to improve in the short term. Two years later, the status of 5 'responders' was that, compared to the baseline before IA1-2018, 3 had an improved total symptom score, 1 had a similar score and 1 had a slightly worse score. I'm not sure that that is enough to suggest 'long term results'.

    Figure 6 gives the symptoms scores for the 5 patients during 12 months of followup after each of IA1-2018 and IA2-2020. Each chart is for a patient for one of the 12 month periods. There are four symptom groups, the lines plot the change in symptom scores. Scores in the grey zone indicate no change or worsening. Bearing in mind that this is an unblinded study, the results are a bit underwhelming. It's possible that three patients got some benefit from the treatment.

    Screen Shot 2023-09-03 at 3.28.54 pm.png

    The authors note that people with ME/CFS treated with a placebo have reported improvements (that's the Norwegian rituximab study), but suggest that this is not what is happening here. They suggest the reproducibility and the long lasting symptom improvement are arguments against that. I'm not so sure when I look at Figure 6 that reproducibility and long lasting symptom improvement were better than what might be expected from a placebo.

    It's good that this group is looking at the auto-antibody possibility. I'd love that to be the answer. But I don't see convincing evidence here. Perhaps it is for a relatively small subset.
     
    Last edited: Sep 3, 2023
    Hutan, Sep 3, 2023
    #16
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