The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
Discuss the article on the Forums.

Cytokine Inhibition in Patients With Chronic Fatigue Syndrome: A Randomized Trial

Discussion in 'Latest ME/CFS Research' started by A.B., Mar 7, 2017.

  1. A.B.

    A.B. Senior Member

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    http://annals.org/aim/article/26078...nts-chronic-fatigue-syndrome-randomized-trial
     
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  2. A.B.

    A.B. Senior Member

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    @Jonathan Edwards do you agree that this adds to the evidence that we're not dealing with an autoimmune disease with inflammatory effector mechanisms?
     
  3. Joh

    Joh Inactivist

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    :cautious:
     
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  4. NL93

    NL93 Senior Member

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    That's what happens when you include people with "severe fatigue" in a CFS study :cautious::bang-head:
     
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  5. JES

    JES Senior Member

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    I don't think this study adds evidence to anything that has to do with true CFS/ME. In fact, the null result was predicted here on PR already years ago.:)
     
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  6. alex3619

    alex3619 Senior Member

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    Let me point out an IL-1 inhibitor can only have an effect if IL-1 is very important. At best this study shows that IL-1 is not a key player. At worst the study is not reliable. It also used subjective endpoints. I wish all researchers would move away from those except as secondary supporting measures. Furthermore I find myself starting to get annoyed these days when fatigue is a primary measure. Fatigue is secondary in ME in my current opinion. What happened to the 2 day CPET or other measures? What about OI, energy metabolism, a qEEG or measuring the post exertional metabolites the Lights found to be abnormal?

    I have said this before, and I will probably keep saying it, we need some specific work to determine what good measures and endpoints are in ME, or at least a discussion of what is not acceptable. This needs to be done by the relevant biomedical researchers. Qualitative findings are fine as secondary measures, but have no place as primary measures.

    I do understand though that research is advancing so fast that any current study measures might be obsolete before the end of the year.
     
  7. Jonathan Edwards

    Jonathan Edwards Senior Member

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    I think this is reasonably robust evidence confirming that CFS is not mediated by the sort of inflammation that is associated with an raised ESR or CRP. In broad terms it confirms the idea that we are not dealing with inflammation in any standard sense. If there is an autoimmune mechanism in some or all cases it looks more likely to be the sort of fatigue mechanism that seems to operate in Sjogren's syndrome or lupus where CRP does not rise or some other fatigue mechanism like myasthenia, although that is clearly a different sort of fatigue.ink this is reasonably robust evidence confirming that CFS is not mediated by the sort of inflammation that is associated with an raised ESR or CRP. In broad terms it confirms the idea that we are not dealing with inflammation in any standard sense. If there is an autoimmune mechanism in some or all cases it looks more likely to be the sort of fatigue mechanism that seems to operate in Sjogren's syndrome or lupus where CRP does not rise or some other fatigue mechanism like myasthenia, although that is clearly a different sort of fatigue.

    However, as Alex points out, IL-1 is only one of several cytokines that are involved in inflammation and the benefit of anakinra in rheumatoid disease, for instance, is not very dramatic.
     
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  8. Joh

    Joh Inactivist

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    Didn't realize Jos van der Meer is involved in the study. As far as I know he's kind of the Wessely of the Netherlands. What I read from him so far were recommendations to think positive, exercise and if you have pain: just think about it less. Looked him up, because the only official new information on CFS we had in Germany in the last years is a translation of one of his articles (done by the Charite in Berlin).
     
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  9. Snow Leopard

    Snow Leopard Hibernating

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    Last edited: Mar 7, 2017
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  10. Valentijn

    Valentijn The Diabolic Logic

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    Yes, and I fully expected the sort of self-sabotage we get from the British psychobabblers when they pretend to investigate any biological treatments. They only engage in such research so that they can proclaim it a failure which should never be investigated again.

    I haven't looked at the methodology yet, but I suspect it's quite poor. In the abstract they already admit the involvement of patients who don't even meet a lax definition of CFS.
     
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  11. A.B.

    A.B. Senior Member

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    The SF-36 physical functioning scores of the sample suggest serious impairment.

    I find it more interesting that they didn't actually measure IL-1 (if they did, it's not mentioned in the baseline patient characteristics or the outcomes). If it's not elevated to begin with, the intervention will probably do nothing.
     
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  12. mfairma

    mfairma Senior Member

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    I took Kineret for eight months or so, following high IL-1 labs, and it definitely was effective. The effect was not massive, but I was much sicker at the time and the improvement was significant at that baseline, and very welcome.
     
  13. Valentijn

    Valentijn The Diabolic Logic

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    Full text at http://annals.org.sci-hub.cc/aim/ar...nts-chronic-fatigue-syndrome-randomized-trial

    Protocol is at https://www.ncbi.nlm.nih.gov/pubmed/26438161

    This seems a bit unusual, since it wasn't crowd-funded at all:
    CBT and GET get plugged, of course:
    It was double-blinded, including blinding the sponsor. This seems to suggest that the sponsor/donor funding the trial was involved in it in some capacity :confused:
    Some mid-trial changes to the methodology, such as the exclusion of long-term CFS patients and allowing unspecified meds:
    Sounds like they changed their mind about an outcome measurement:
    Patients were recruited using Fukuda. The abstract may have merely been unclear on that point. But the exception for the 10 year limit stinks a bit of doing contortions to find ways to exclude and include specific patients:
    Only subjective outcome measurements were used:
    A diagram shows the exclusions. Indeed, the "10 years of fatigue unless it got worse recently" excluded exactly 1 patient. 4 were excluded for meds, and 12 for co-morbidity. The Beck Depression Inventory was used, which equates disability with depression - if you can't do something, it's taken as a sign of depression. So more disabled patients were likely excluded as a result.

    They're saving the objective data for another day, a tactic also used by Dutch psychobabblers when they needed to bury null actometer outcomes:
    This is blatant bullshit, and they cite to the study that proves it. The difference in inflammatory markers was happening at the 3-year point, not after 10 years:
    One of the few intelligent things they've said:
    The Anakinra group did have a larger improvement in SF36-PF of about 10 points compared to 5 points for the controls. It's also bizarre that every single endpoint score (Table 2) has a range for the standard deviations which is identical for both groups. Unless I'm missing something very basic, there seems to be a major problem with those figures.

    The conclusion isn't as bad as I was expecting:
     
    Last edited: Mar 8, 2017
  14. Solstice

    Solstice Senior Member

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    Ah good old v.d. Meer en Knoop getting a last few papers in before their empire finally crumbles at the end of the year/beginning of next year.
     
  15. alex3619

    alex3619 Senior Member

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    Next year is looking like it might be a good year. :whistle:
     
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  16. charles shepherd

    charles shepherd Senior Member

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  17. charles shepherd

    charles shepherd Senior Member

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    Clinical trial from the Norwegian group involving etanercept - which inhibits tumour necrosis factor:

    https://clinicaltrials.gov/ct2/show/NCT01730495

    NB: This trial was terminated after 2/4 patients developed what was described as a moderate exacerbation of symptoms
     
  18. MeSci

    MeSci ME/CFS since 1995; activity level 6?

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    It's unusual that this trial was reported in Physician's First Watch - they don't usually deal with CFS. Here is the write-up from there yesterday:

    No Benefit of Rheumatoid Arthritis Drug in Chronic Fatigue Syndrome
    By Kelly Young
    Edited by
    - David G. Fairchild, MD, MPH, and
    - Jaye Elizabeth Hefner, MD

    The interleukin-1 receptor antagonist anakinra doesn't seem to reduce fatigue in women with chronic fatigue syndrome, according to a small trial in the Annals of Internal Medicine. Anakinra was approved in 2001 for rheumatoid arthritis.

    Fifty women with chronic fatigue syndrome that included severe fatigue and functional impairment were randomized to receive daily subcutaneous injections of either anakinra or placebo for 4 weeks. After treatment, the primary outcome -- fatigue severity -- was similar between the groups. Both groups saw improvements in fatigue over time, but most patients were still severely fatigued during the 24 weeks of follow-up.

    The authors say it's possible that concentrations of anakinra were not high enough in the brain to have an effect; additionally, interleukin-1 may play a limited role in chronic fatigue syndrome.

    Link(s):
    Annals of Internal Medicine article (Free abstract) http://response.jwatch.org/t?ctl=13CB2:5FF9B588B7CB016CE2D6905BEE2746EA&
    Background: NEJM Journal Watch General Medicine coverage of anakinra for rheumatoid arthritis (Your NEJM Journal Watch registration required) http://response.jwatch.org/t?ctl=13CB3:5FF9B588B7CB016CE2D6905BEE2746EA&
     
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  19. Kalliope

    Kalliope Senior Member

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  20. Dr Speedy

    Dr Speedy

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    Patients who did not have a post infectious onset were included in other words patients who did not have the disease ... As usual setup to fail instead of set up to find out ...
     

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