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"Rituximab in CFS: More research needed" letter in PlosOne

Discussion in 'Rituximab: News and Research' started by Sasha, Oct 28, 2011.

  1. Sasha

    Sasha Fine, thank you

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    The link is down but here's the text of the letter on the ME Association's site.

    Their main point is that they want more double-blind, rather than open-label trials.
  2. Nielk

    Nielk

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    I read that letter earlier and to my unprofessional little functioning mind, it makes a lot of sense.
    We are talking here about a very dangerous drug. There have been deaths resulting from taking it. The fact that they bring up about such a delayed reaction, not seen with any other disease they have studied is worrisome. We learned our lesson with XMRV, not to jump to conclusion too fast before double blind studies have been performed.
    kurt likes this.
  3. Sasha

    Sasha Fine, thank you

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    I agree there are a lot of reasons for caution - it's good to know that more research is going ahead. I think that's a good combo - caution and research, as long as it's good quality and happens fast.
  4. wdb

    wdb Admin

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    They all seem like valid sensible observations to me too.

    But what I don't get is why the hell no one criticised the PACE trial for the same things, not only was it not double blind or even single blind, had a non comparable control group, and used the Chalder scale which also measures change in fatigue, where were their methodological concerns when that was published.
  5. Esther12

    Esther12 Senior Member

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    Yup.

    People here had raised concerns about the difficulty of genuine blinding with a drug like Rituximab and the danger of placebo affects distorting results, the difficulty of assessing improvements, etc, etc. Some researchers only seem interested in making these sorts of criticisms of non-psychiatric CFS work, while trying to ignore the problems with research like PACE. Their talk of the needing a theoretical justification is particularly amusing in light of the way research undermining the role of both deconditioning and fear of activity as perpetuating factors in CFS was addressed in the Lancet's accompanying PACE editorial.

    edit: One of the authors is Action for ME's medical advisor, who has only spoken out in support of PACE. What a joke they are.
    Megan likes this.
  6. redo

    redo Senior Member

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    Many? Handful is more the word. Some. If they sat tight, I bet you could fit them all into a minibus. And the numbers of CFS sufferers are more than the Ohio Stadium times ten, and that's just in US.
  7. Nielk

    Nielk

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    I agree that it's biased and unspeakable that PACE was not thrown out first hand but, is that a reason not to be cautious with any other study?
    kurt likes this.
  8. Battery Muncher

    Battery Muncher Senior Member

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    No, and you're absolutely right - caution is critical here. In fact, it may well be the most important feature of future trials. Safety is vital.

    Still, I think it's worth flagging up the hypocrisy, if only to flag up how badly conducted PACE was. The science behind current treatment is terrible, yet no-one seems to have noticed except the ME sufferers.

    So I think it's useful to compare PACE with the Rituximab, to show that the psychiatric establishment hasn't got a leg to stand on - at least when it comes to criticising the rigour of the latter trial.
    ixchelkali and justinreilly like this.
  9. kurt

    kurt Senior Member

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    The cautions in that letter make perfect sense, RTX presents significant immediate health risks, and ME/CFS patients need to be careful not to draw premature conclusions as has happened before. However, given the way pharmaceutical medicine works today, I think there is an even greater long-term risk if premature conclusions are drawn. Those who want ME/CFS to just go away could point to RTX therapy and say 'there is already a treatment, we know what causes CFS' and then slow funding for other research directions, considering our case to be closed. But of course the improvement on RTX was not very dramatic in most of the cases, only a few total remissions, which puts RTX therapy in the same category as several other ME/CFS therapies.

    The longer delay they mentioned is the best point raised I think, that should be better understood before any therapeutic use. RichVank has proposed an interesting hypothesis about the long delay, which makes sense. But of course those researchers would not know about the methylation problems unless they were keeping track of the ME/CFS community...
  10. Roy S

    Roy S former DC ME/CFS lobbyist

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  11. eric_s

    eric_s Senior Member

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    I'm not Dutch, but as far as i know Van der Meer is the Netherlands' equivalent to Wessely. So this does not really come as a surprise. I don't know much about Dedra Buchwald, but i remember her name from a Komaroff presentation and i think there she was mentioned as an author of some interesting research.

    I'm not qualified to make a judgment, but i think everyone probably agrees that more research is needed. And hopefully it will not take for ever for it to happen. What type of study is the best thing to do i will leave to the scientists, if Van der Meer and colleagues don't think Fluge and Mella are doing the right thing and they are not open to Van der Meers arguments, then i guess Van der Meer should just do his own work on Rituximab and let the others make their own decisions.

    I think Fluge and Mella did exactly the right thing after making the observation that one of their patients who also had ME/CFS improved after treatment with Rituximab. If with that drug it's not possible to blind a study 100% then that's not their fault. Sure they could have included such a question, but i guess with every study there something that could have been done better. And let's not forget that it took from 2004 until now for that study to happen and be published. That was when Fluge and/or Mella made their first observation of an improvement in ME/CFS symptoms after Rituximab treatment. The problem we have here is definitely not that somebody is pushing ahead too quickly... :rolleyes:

    I have not read the paper but from the articles covering the study, i think the successes were dramatic 2/3 of cases have showed improvement and some total remissions. In a sample of 15 persons. If placebo can explain that kind of improvements, especially total remissions, then show me that in the PACE trial and similar studies... Or in people using homeopathy etc.
  12. Sasha

    Sasha Fine, thank you

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  13. FancyMyBlood

    FancyMyBlood Senior Member

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    Thanks Roy, very interesting!

    @ kurt and others

    About the side effects of rituximab... The authors (Mella and Fluge) reference a review of rituximab use in RA and it's well tolerated with no increasing rate of serious infections. So while it's good to be cautious I think the 'horror stories' are way overblown.
  14. Esther12

    Esther12 Senior Member

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    I think PACE has made me much more cautious about trusting the claims made as part of any study!
  15. Dolphin

    Dolphin Senior Member

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    It'd be worth somebody making that point if anyone wanted to have a go. You don't have to have lots of references in a reply - often they won't want any but you can always copy one or two of the references already there e.g. Fluge paper and/or PACE Trial paper to make it look like a referenced point. I've other things to be doing I'm afraid.
  16. Dolphin

    Dolphin Senior Member

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    Another point it might be worth mentioning on that thread. Anyway, I should probably stop making such suggestions. I'm just trying to point out that people can comment directly if they want.
  17. eric_s

    eric_s Senior Member

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    I hope they will find out why the reaction was like this, but i guess this is also a point against a placebo effect having caused the observed results. I don't think there's a 6 to 10 months delayed placebo effect.
    justinreilly likes this.
  18. Dolphin

    Dolphin Senior Member

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    You could have a point. At the same time, in this case, they only got two dosages close together; it could be the case that a different regime might produce better results.
  19. Daisymay

    Daisymay Senior Member

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    The researchers commenting on the Mella/Fluge paper are Wesselyites supporters.

    Jos van der Meer is the Dutch version of Wessely.

    You can read Dr Alastair Miller's (Principal Medical Advisor to "Action for ME") and Dr Brian John Angus' views on the PACE trial in this Science Media Centre press release from earlier this year:

    http://www.sciencemediacentre.org/pages/press_releases/11-02-17_cfsme_trial.htm


    Andrew Lloyd has collaborated with Reeves and with Wessely:

    http://www.cfidsreport.com/News/10_Reeves_History_CFS.html

    Myth 3

    "Lloyd and his collaborators were far more forthcoming with speculation about CFS than Reeves. Long before Reeve's chose Lloyd as a collaborator, Lloyd's published work failed to reveal any signs of predilection toward a viral model for CFS. Lloyd wrote: "Current evidence suggests disruption of fundamental central nervous system mechanisms, such as the sleep-wake cycle and the hypothalamic-pituitary-adrenal axis, may underpin the clinical features of this disorder." (3) In one of his most widely covered papers in 1994, he stated: "Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables" (4). The list goes on, and the list is long.

    History will judge virologists involved in CFS (such as Andrew Lloyd, Stephen Strauss, William Reeves) NOT by how well those virologists were able to detect XMRV, Epstein-Barre, or any other virus. Instead, history may judge them on how accurately they interpreted their own viral research. History will also evaluate whether their beliefs/attributions influenced their sample selection. Until a biomarker for any disease is found, the attributions and feelings of the researcher toward those who suffer from the disease has a much greater bearing on their conclusions than tests. The clinical beliefs and observations are the foundation of their sample selection and conclusions."


    Dr Matthew Buckland is a consultant immunologist at St Bart's Hospital where Professor White works. At this link, it seems he is doing research with Prof White on cytokine research in CFS/ME:

    http://www.mrc.ac.uk/Utilities/DeclarationsofInterest/MRC006490?forumid=331851

    Now when that research is published I wonder what it will show? Perhaps that there are no cytokine abnormalities or that any abnormalities can be corrected with CBT/GET ?
  20. SilverbladeTE

    SilverbladeTE Senior Member

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    Somewhere near Glasgow, Scotland
    KFG
    as I keep saying, the "Psychobabblers" are...well, "witch finders" from the 1500s
    they will bend the facts to fit their insane beliefs, regardless if thsoe facts prove them to be full of "equine manure"
    So how DARE anyone show they are full of "ureaic acid excreted in liquid suspension"!
    Only the Great God of Psychology with his noodly appendages knows THE TRUTH!
    *cue lightning bolt from Olympus,or, more likely, Deep R'lyeh*
    ;)

    *Silverblade smuggles out some ME patients under the eyes of the Imperial Stormtroopers on the way to the Rebel base in Norway*
    "These are not the heamorrhoids you seek!...They're over there sipping cianti and debating the Emperor's Clothes, you know, Freud n' stuff!"
    :D

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