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SBM: Kogelnik, Rituximab and CFS: Jumping the gun

Discussion in 'General ME/CFS News' started by Firestormm, Jan 13, 2013.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i dont even think they know how ritux works in RA or other autoimmune disorders but treatments with ritux isnt an issue. I believe dr k is doing extensive labs and looking closely at different aspects of the immune syste. I guess this is going to help him work out who is a candidate for treatment and who isnt as well as follow the progression of the disease alot closer with more advanced tests, he may them have answers has to how ritux is helping cfs/me which might direct him to the cause, maybe better treatments. Also dr k isnt just some doc the pulled out of a cornflakes packet, he seems very credentialled to do such work. there is no one doing this sort of work and it needs to be done. :thumbsup:
    penny, Valentijn and lnester7 like this.
  2. Firestormm

    Firestormm Senior Member

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    This ain't about Dr Kogenik being a capable doctor or about the emotional motivation that we have as patients for treatment (any treatment). Or about whether or not we as patients are capable of making an informed decision.

    As a patient I want a treatment that works (or has been shown to have a good chance of working). I want the treatment to have been approved for use in my condition. So I have an emotional investment in Rituximab. No question. No argument.

    The issue was about 'jumping the gun' and whether or not it is reasonable to prescribe Rituximab (specifically) for someone with a diagnosis of ME. At this point in time given the incomplete research that has occurred to date.

    Some of this concerns expressed in the article are very very relevant to the concerns that WILL be expressed should Rituximab progress beyond the stage it is at now. Our 'community' will need to engage with some skeptical opinion and meet the demands of regulators.

    I am in receipt of 'off-label' drugs. They are known entities for the treatment of some of my symptoms. Rituximab is an unknown at this point. It is not known if Rituximab has been 'successful' because it e.g. addresses the cause of ME or because it targets one or more of the symptoms.

    We don't know. Caution appears to be the watchword but it doesn't seem to deter (and neither apparently should it) doctors prescribing such treatment for some of their patients.

    I would like to know because I am interested how they determine if a patient is suitable, how they monitor the effectiveness of the drug and how they determine is the drug is leading to improvements or is responsible for any deterioration.

    Anecdotal reports of feeling better are great and useful but it needs to be quantified and their needs to be something with which to compare e.g. a control of some description. Or else how does anyone know if the drug is really working?

    Actually, what is it that this drug is meant to do? If it 'kills off' your B cells then are you more likely to pick up infections? Will you be more susceptible to 'crashing' as a result? I freely admit at this point and without reviewing what I have read - that this scares the crap out of me.

    But if my NHS GP or either of the medical consultants I see were to offer me this treatment at some time in the future I would give it a whirl. But I need that degree of reassurance - speaking personally. In my first few years with this diagnosis the chances are I might well have embarked on treatment when in the States.

    So I do 'get it'. But I am trying to separate myself from the emotional, desperation fuelled, hope that Rituximab possibly offers; and trying to view things objectively by asking questions.

    I don't have a beef with Kogelnik but on balance I do happen to think he and others should be treating patients within a trial or pilot study rather than individually. I think it would be better for him and for patients if all this effort and experimentation (and cost) were to have a purpose beyond individualism.

    Kogelnik must have a theory, a hypothesis as to why he believes this drug is as effective for some of his patients as it might seem. I'd like to read about it.
    ibenagnes likes this.
  3. user9876

    user9876 Senior Member

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    I read stuff a little while ago so can't quite remember but there has been discussion on other threads.

    I read a paper by Jonathan edwards on Rituximab and RA where he talked about the disruption of an immune cycle. T Cells cause RA in that they are the things that attack the joints but his theory was that there are signaling mechanisms from B cells that go wrong and hence killing off b cells reduces the auto immune reaction.

    Strangely infection rates don't seem to increase massively. I'm pretty sure I read something talking about redundancy in the immune system as a possible reason for there not being an increase in infections.
    Firestormm likes this.
  4. orion

    orion Senior Member

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    Eh? So let me get this straight. You're saying that in order to "engage" (whatever that means) with the people who can effect changes in political, research and clinical attitudes that would advance the interests of M.E/CFS patients, we have to pretend to support the status quo. That makes no sense whatsoever. How can we meaningfully argue for change when we're simultaneously pretending not to support change in order to make ourselves more acceptable to the other side?

    Also, I don't believe that the "norms of medical ethics" are widely accepted, at least not outside of medicine. Many aspects of medical ethics are clearly out of step with the values of the rest of society.
    alex3619, penny and Valentijn like this.
  5. barbc56

    barbc56 Senior Member

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    I have sleep apnea, restless legs syndrome and excessive daily sleepiness. I have to get an authorization from my doctor for my insurance to cover the costs. Even then, it's expensive.:)
  6. satoshikasumi

    satoshikasumi Senior Member

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    Unfortunately, the problem is that the same "widely accepted norms" have permitted ME/CFS to be marginalized and to receive levels of research funding more than an order of magnitude lower than other illnesses, including mental illnesses, with a similar burden on society. If only scientific priorities were set in a fair and objective way.

    I believe that science eventually progresses toward the truth, but there is no guarantee it will happen in anyone's lifetime on a particular matter.

    While the cult-like mentality surrounding XMRV bears similarity to the fervor surrounding the vaccine-autism hypothesis and similar debacles in other diseases, the difference is that other diseases have a mainstream point of view that can counterbalance the fringe elements.

    With ME/CFS, there is no "establishment" and no "mainstream view" and no "consensus." There is simply an aura of societal indifference. And no funding for any kind of significant research effort.

    The effort to debunk XMRV was a rare exception to the rule- little or no attempt is made to replicate or validate most findings in the ME/CFS field. For example, there is still no real consensus on the role of low natural killer cell function, first identified more than twenty years ago. Same with reduced exercise capacity- some scientists assert vehemently that work capacity is reduced, while others think the fatigue in this disease is entirely caused by the brain. Are there subgroups? Again, some researchers thinks there are subgroups so distinct that ME/CFS is actually multiple discrete diseases. Other researchers think ME/CFS has exactly the same cause as other functional somatic syndromes like FM, IBS, MCS, GWS, and somatoform disorders. We have as little consensus as we did when the 1994 CDC definition was developed. Don't mistake a trickle of data for progress.
    penny, TessDeco and Valentijn like this.
  7. satoshikasumi

    satoshikasumi Senior Member

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    What's the author really getting at here? Is it unethical to:

    -prescribe drugs off label for ME/CFS?
    -prescribe an expensive drug for ME/CFS?
    -prescribe a drug with possible rare but serious side effects when it is unproven?
    -Represent to ME/CFS patients that they are receiving the drug as part of a pilot study when there is no IRB approval for the study?
    -Represent to ME/CFS patients that they are receiving the drug as part of a pilot study when there is no external funding for the study?
    -Treat patients who travel from the other side of the world to seek care?

    She states Kogelnik is unethical, and mixes up all these reasons in the article. I would have given the piece more credit if she would explain what ethical rule she is applying to the case, how it applies, and what he could do differently.
    penny and Valentijn like this.
  8. searcher

    searcher

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    I read through the comments and the author recently posted (in response to @Hip's very articulate comments) that "My personal guess is that we will eventually learn that a few patients with an objective disease are being lumped together with a lot of people who have somatoform disorders and psychological problems. Until that can be sorted out, research just adds to the confusion." So she may have some reasonable criticisms but the reason her argument seems so jumbled is likely because she simply doesn't see the point of giving drugs or doing research on a bunch of psych patients who she thinks are imagining they have a disease.

    On a related note, I am a patient of Dr Kogelnik. I am not taking Rituximab and think he does a fine job pointing out the risks of potential treatments. And, as others have pointed out, he wants to do a double-blind study but as far as I know doesn't yet have the funding. I was going to post on the article but trying to reason with people who want to ignore all physiological findings doesn't seem very useful.
    penny, Enid, Valentijn and 1 other person like this.
  9. alex3619

    alex3619 Senior Member

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    I do not think this is more than an heuristic. I think that IF someone notices something, or IF they have an alternate explanation, or IF some new findings clearly contradict the old, THEN we get change, and in many cases this will be closer to the truth. The point though is that all of these involve challenging the status quo. Positive change (and negative change) require that someone is challenging the current position.

    Working with the current entrenched position can typically only achieve small changes. Challenging the entrenched position is required to effect more substantive change.

    I do not object to people working to make things better within the established system. We need them too, they help optimize the current systems effect. What I disagree with is that this excludes others working to make bigger changes to the system. Its not either/or. We need both.

    When things are wrong they only can get fixed if they are seen. This is the idea behind the principle of transparency. When things are broken, having been seen by some to be broken, they only get fixed if people act to fix them. This is the idea in part behind the principle of accountability.

    To argue that we should not ask questions, challenge false claims, and challenge broken rules, regulations or attitudes, is counter to the principles of transparency and accountability. I will have much more to say on this very soon, that is as soon as I stop finding treasure troves of information on this issue.

    There is nothing wrong with people asking questions about Rituximab and its use. We need information so that we can decide is something if wrong and needs fixing. What is a problem is that sometimes limited information is used to push an agenda, and that uncertainty behind conclusions is not clear.

    I am always in favour of making more information public. Lets start with all data from all clinical trials and go from there, perhaps?

    Bye, Alex
    WillowJ likes this.
  10. barbc56

    barbc56 Senior Member

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    . http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836889/


    Dr Kogelnik's way of prescribing Rituximab to me/cfs patients doesn't come close to the above standards. I will be adding some more thoughts tomorrow as I have found some other interesting resources. I am very tired but I think the above is very informative so wanted to post this as soon as possible.

    Barb
  11. Firestormm

    Firestormm Senior Member

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    This is what I was trying to say, pretty much, about my own prescriptions for drugs that are not specifically recommended for ME. They are widely known about for specifically targeting what are generally seen as symptoms associated with me as an individual. They are relevant to me and whilst are thought to also be relevant to ME - they are treating symptoms.

    The Gabapentin I mentioned earlier in the thread was prescribed wholly for the acute headaches I was experiencing - especially in the mornings. My 'pinata-head' periods. Gabapentin has a track record. There is some evidence of it being of use in some people with my primary condition of ME - but it is not considered a treatment for ME itself. There is more evidence of it's benefit for people with Epilepsy and as part of my problems have indicated a leaning towards that issue - it seemed an appropriate prescription for me and worth trying.

    Similarly, my Baclofen, were prescribed also for the 'restless legs' and involuntary muscle spasms I was experiencing. Same too the Betahistine Hydrochloride - for the nausea and 'dizziness'. These are drugs with a record for treating these symptoms but they remain something to try and see if they work.

    Not specifically something everyone would have or be recommended purely because they have ME, but something that might be considered worth trying based on a personal consultation. At this present moment in time - Rituximab is not. We don't know the aetiology of ME so we don't know what Rituximab is trying to target that might be relevant. Is it targeting a symptom or the disease itself?

    Rituximab is not on the radar for ME or any of it's known symptoms. Only research properly conducted will see this change. It is also expensive. Can't get away from that either. If we want this drug to get onto the radar someone will have to either discover and then prove exactly what it is doing, and how effective it is, and establish the safety profile; and/or try to address the cost-effectiveness concerns that are bound to be raised. Delivery of treatment is another consideration that might need to be looked into with the manufacturers as this delivery will be a large factor in terms of cost.
  12. Valentijn

    Valentijn Activity Level: 3

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    Sorry, but you really don't know what Gabapentin is doing. No one does. "Gabapentin was initially synthesized to mimic the chemical structure of the neurotransmitter gamma-aminobutyric acid (GABA), but is not believed to act on the same brain receptors. The mechanism of action that leads to its rapid analgesic effect is simply unknown."

    Neither the UK nor the US indicate headaches as an on-label usage. Even for people who "have indicated a leaning towards" epilepsy. In fact, the company that developed it got in serious trouble for heavily marketing it for off-label uses - the settlement of the case cost the company $430 million.

    "The precise mechanism of action of baclofen is not fully known." It's indicated for use in MS spasticity, and potentially for spinal cord injuries and diseases in the US. No mention of them being approved for spasms or restless leg syndrome in the US. In the UK the language is a bit broader, but still limited to spasticity. Please note that spasms and spasticity are different things - spasticity refers specifically to involuntary muscle stiffness making it difficult to move the affected limb.

    Betahistine is used only for Meniere's disease on-label in the UK, as far as I can tell, to remove excess fluid from the inner ears. Any other use would be off-label.

    Two of the medications you are taking are clearly off-label (unless you have Meniere's with your ME/CFS). The third one probably is too (even if you might have "a leaning toward epilepsy") because you are taking it "wholly for the acute headaches." Very little is known about how one of those drugs works at all, and another is only partially understood.

    I'm not pointing this out to attack you, or your choice of medications, or your doctor's decision to prescribe them. To the contrary, I think that symptom management is extremely important for us, and I'm glad that you've found things that help. I'm merely pointing out that:
    1. drugs are very frequently prescribed off-label to the general public
    2. drugs being prescribed to ME patients for ME symptoms are almost always off-label
    3. drugs (like gabapentin) are often prescribed with virtually no knowledge of how they act
    4. drugs are almost never completely understood, even when there is some knowledge of mechanism
    So to apply much higher standards to Rituximab would be ridiculous, especially when there's more support for its use in ME patients than there is for other drugs frequently prescribed by mainstream physicians. It's known that it depletes B cells, which puts it leagues ahead of gabapentin when it comes to understanding the effect it has. There has even been specific research in ME patients demonstrating how a drug which depletes B cells might have a beneficial effect - due to abnormal B cell sub-populations.

    I'd say those ME patients and physicians prescribing Rituximab to them are making a relatively well-informed decision, especially compared to much of what's available to us via mainstream doctors.
    penny, SOC, alex3619 and 3 others like this.
  13. Enid

    Enid Senior Member

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    I second Valentijn's thoughts on Gabapentin (quite how it works). When pain was intense and sleep impossible I was put on low dose by my GP for pain only with no relief until raising the dose to epileptic levels over a period. The result was a period of sound sleep (rising only to eat little etc) and feeling somewhat better afterwards for it. My docs (sadly not the the Kogelniks of this world) hadn't a clue as to why. All for his INFORMED approach.
    penny and Valentijn like this.
  14. Firestormm

    Firestormm Senior Member

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    Val, I do agree with much of what you say, not with the conclusion though. I know that my drugs are off-label - I wasn't arguing against this. FYI Gabapentin:

    Also, Gabapentin/Neutontin

    With regards to the Baclofen. I recognised it as a muscle relaxant and indeed it seems to work in that capacity. Your source would also indicate this is so. There is also an added benefit - it that it helps to relax the bowl spasms I experience. Very painful and paralysing.

    Betahistine. Thanks for the extra information. As part of my original diagnosis persistent labyrinthitus was diagnosed as a result - it was thought - of the original infection. The effect has been to help overcome the nausea and to help with the balance issues.

    When visiting a GP he/she will refer (in my experience) to their own literature and to their own experience and knowledge. Same goes for consultants for that matter. Those specialising in our ME will - it is expected - have a better appreciation of the kind of drugs that might help.

    GPs and consultants can choose from a vast range but by and large I would suggest they know the drugs that are considered most appropriate for the condition, the symptom treatment and for their patient.

    I have not on this thread doubted this was the case for Dr Kogelnik and Rituximab. Not once. I am saying however, that I personally do not feel there is enough evidence or knowledge about how this drug can possibly work for people with my condition.

    Now, in the UK I would very much like to learn why it would be considered inappropriate to prescribe Rituximab for ME compared to the decision in the USA to do so. If a doctor is questioned over their decision to prescribe me or anyone else the drugs that they are on - then the doctor has to justify his decision.

    That decision - in the case of off-label drugs - is I would suggest more likely to be questioned that not. And for Rituximab it is worth asking. We are not guinea-pigs! Yeah it's great that in the USA and elsewhere and from the internet you can get pretty much whatever you like so long as you can pay for it.

    But consider for a moment those who would like to try Rituximab but cannot afford it. Or people with your condition who want to see it scientifically proven that Rituximab actually works and is not another speculation.
  15. lnester7

    lnester7 Seven

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    I know it doesn't feel useful but reasonable people that will read the article and hear our side of the story. We will gain the war with small battles. Is small advocacy and we need to make people think twice before they report nonsense. So please don't be shy to express your opinion, As a group we need to fight back in any way we can.
    WillowJ, ukxmrv, SOC and 1 other person like this.
  16. In Vitro Infidelium

    In Vitro Infidelium Guest

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    Engage with: engage with someone/something to make an effort to understand and deal with someone or something or as an alternative - engage with someone: to start to fight an enemy in battle.
    I’m puzzled about your direction of thought. Is your view that to advance the interests of M.E/CFS patients, that both the scientific method and the published ethical standards under which both modern medicine and medical research operate, have to be aggressively challenged ? Even if (and I can not see in what world it possibly could be the case) that there was some value in tying M.E/CFS advocacy to the kind of monumental challenge you appear to want M.E/CFS affected people embroil themselves in; to attempt such a challenge without attempting to talk to the people who routinely operate under these disciplines, in terms that are meaningful to them, would render the whole process pointless. Frankly I think what you seem to be arguing for has more in common with the plot of Starwars than any viable advocacy strategy.
    If you are intent on making an appeal to some notional ‘masses of the world’ as the basis for your preferred replacement for current medical ethics you will no doubt get an answer of which you approve. That isn’t going to get around the fact that politicians, researchers and clinicians have their collective starting points at the status quo. You can shout at them from your populist ramparts but don’t expect them to listen or take you seriously.

    IVI
  17. In Vitro Infidelium

    In Vitro Infidelium Guest

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    I actually agree with much of what you’ve written, except unfortunately your starting point: that the same "widely accepted norms" have permitted ME/CFS to be marginalized and to receive levels of research funding more than an order of magnitude lower than other illnesses, including mental illnesses, with a similar burden on society.
    Neither the scientific method, nor medical ethics have operated in the way you suggest. There may well be societal norms that underwrite the position that M.E/CFS patients find themselves in but that surely only leaves us with the unremarkable statement that history has produced the present. What seems far more pertinent to me are the questions a) what needs to be changed ? and b) what can be changed ?

    Trying to seek change in how science operates or the structure of medical and medical research ethics, even if a case for change could be articulated, falls on the question of ‘what can be changed’ at least as far as M.E/CFS advocacy is concerned. It is simpy beyond our capacity. Personally I don’t think we are the same position as 1994, not because the science of M.E/CFS has changed, but because science and medicine have made progress separately from any focus on M.E/CFS. The rapid advance of genomic science is particularly relevant because it offers new ways to consider and investigate M.E/CFS. This and other changes in scientific capability don’t of themselves improve the position of M.E/CFS science but they do offer a different context in which to present a case for more definitive investigations of M.E/CFS, including properly organised multi site replication work.

    One of the things that M.E/CFS patients have in their power to change is the way they interact with those who may have interest in the illness, and who may in turn actually be influential with politics, service delivery, research and treatment. My whole argument in this thread revolves around getting people on our side and communicating with them on their terms, rather than treating everyone who doesn’t declare themselves as ‘one of us’, to be ‘the enemy’. The status quo is obviously not where ‘we’ want to be – but no matter how much we dislike it, it is where we have to start from.

    IVI
    barbc56 likes this.
  18. Enid

    Enid Senior Member

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    It's rather simplistic to think we think in terms of "enemies" for ME - on the contrary we follow the increasing revelations in scientific discoveries - should the anti hard science appear it lays itself open increasingly now to ridicule and indeed worse. We are concerned about the real understanding of the illness myalgic encephalomyelitis now increasingly exposed - if a clique (psychos) attempt to pervert the real course of science they need re-education. Sad that we are forced to do it.

    But perhaps you have no idea about the situation in the UK.
    ukxmrv and Valentijn like this.
  19. searcher

    searcher

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    lnester7

    Thank you, this is a good point. I think I just got frustrated because I had spent time formulating a response and then felt blind-sided when I saw that the author is making her arguments from the position that CFS is just a modern form of hysteria. I hate that the "skeptic" community is generally so blindly accepting of outdated 1800s views on health conditions. I will try to muster the energy to post later today.
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  20. lnester7

    lnester7 Seven

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    what I usually do is say "please do research before doing an one sided view reporting" or whatever is relevant, then I post links to any relevant studies / publications from reputable and respected journals.

    I sympathies with your frustration, but we can't let them wear us out!

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