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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. penny

    penny Senior Member

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    Your presumed litmus that it is only ethical to prescribe a drug that we know is safe and know will help, is unsatisfiable. Zero treatment options for anyone, for any disease would meet this criteria.

    I think Mark said it best:
    I can't believe we're seeing a replay of this scenario -- attack those who are trying to help us. Though interestingly it does seem to be many of the same folks wielding the torches and pitchforks. I guess I'd naively hoped the last witch hunt was an aberration.
     
  2. user9876

    user9876 Senior Member

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    The question is what is a reasonable generalisation and how could we improve knowledge. Rituximab has been tried on many people with quite a variety of disease includine ME - although not necessarily treating ME. Why make that particular divide rather than a different divide say based on peoples genetic structure. Rituximab has been used for many different diseases including a number of auto immune disease as well as lymphomas. Should other drugs such as pain drugs specificaly be trialed with ME separately from other conditions? Was there ever a trial looking at the safety of ibupofen or paracetamol with ME.

    I would argue that the most important thing is to study mechanism and gain a better understanding of the immune system. Perhaps comparing the way the immune cycles are disrupted with RA and ME using Rituximab. This means having good measurement systems.

    You suggest clinical studies would help develop a safety profile. They may help with short term effects but very rarely with the longer term effects. Unless you run a trial for many years in which case you just delay treatment. This is the reason there is a need for better adverse effects reporting and for doctors to take events they see seriously. This is quite a challenge.

    So this poses a question of how much more information about risk would a trial really bring. Its an area probability theory doesn't help with and comes more into possability theory where unknown unknowns can be represented. For any drug though there will always be the blackswan type risks. We take many risks everyday, the question should be around what risks are reasonable.

    Chemo is about poisoning the body so of course it is dangerous. If you have cancer treatment then the doctor will warn of these problems - they will have seen the problems them selves. From a friends experience I can tell you that the warnings around Rituximab are much much less than other chemo and BMTs etc

    Monitoring only helps if we know what to look for. I know after some forms of chemo patients would be very closely monitored (say in twice a week for blood tests). However as I said before Rituximab seems to be one of the less potent and safer chemo drugs and with it less intensive monitoring.
     
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  3. barbc56

    barbc56 Senior Member

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    Yes. By safe I mean you take into consideration the benefits plus the risks. All medications as well as supplements come with risks and that needs to be weighed by the patient and Dr. for any treatment.
     
  4. barbc56

    barbc56 Senior Member

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    May I have a source for that? Thanks.
    Barb
     
  5. penny

    penny Senior Member

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    Right, and there's no reason to think that's not exactly what's happening with these patients who have decided to take this particular med. So for those people this drug fulfills this particular definition of safe.
     
  6. user9876

    user9876 Senior Member

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    Its just personal experiance of how a friend with leukemia has been treated with various rounds of chemo, BMT, rituximab.
     
  7. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    We can say wait for the research, but who is doing the research?? nobody, as funding has dried up for the Norway research. Dr K i think is trying to get evidence that ritux works and with enough evidence he may then get funding for more extensive research for ritux and cfs/me.

    As for off label treatments being unethical, well that makes every treatment for cfs/me unethical as there is nothing approved for cfs/me, so antidepressants, antivirals, antibiotics, sleep meds, antihistamines, docs shouldnt be giving us anything then.

    If someone has the ability to think and make informed decisions and their doc has explained the associated risks of the treatments then i say go for it.

    The first do no harm medical saying could also be used for those docs who refuse to treat cfs/me as not treating causes harm.

    RA also has a nk cell dysfunction similar to cfs/me, so i think is ritux helps them its quite possible that similar effects will happen with cfs/me.

    I dont understand why people are shooting down a possible treatment for cfs/me, if people start improving on ritux from dr K then its going to open up treatment avenues for all of us, why would we want to close this down???
     
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  8. satoshikasumi

    satoshikasumi Senior Member

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    1. Dr. K gives patients pages and pages of informed consent about the risks of rituximab, and he explained fully that the treatment is unproven and the evidence is limited.
    2. Most of Dr. K's patients who are not rich are not paying for rituxan. They are paying only for infusion costs and the fee for the doctor's visits, which are not in excess of the rates charged by other physicians.
    3. There is no evidence he is "recruiting" patients to take rituxan. He is simply allowing well-informed patients access to a drug they are already demanding.
    4. There is no evidence he has a financial interest in rituxan. How is this worse than what any of the other ME/CFS docs are doing? A doctor has a choice with these patients: offer them something unproven or offer them nothing.
    5. An N=1 clinical trial is a scientifically valid concept. It is much less persuasive than a placebo-controlled trial, but it also gives individualized information about responses (rather than simply measuring average responses). Dr. K uses actometers to objectively measure his patients' improvement. It will be quite convincing if there are some patients who improve when they are on rituxan, worsen when they are off, and improve again when the drug is resumed. Especially when we know that CBT/GET doesn't increase activity measured by an actometer.
     
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  9. satoshikasumi

    satoshikasumi Senior Member

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    Finally, Dr. K and the Open Medicine Institute's top priority is funding a randomized controlled trial of rituxan, rituxan+valcyte, valcyte alone, and placebo. It is perfectly logical to start with a small case series to inform how to design a trial protocol. Nothing unusual or wrong about what Dr. K is doing. He fully agrees that a larger study is necessary.
     
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  10. user9876

    user9876 Senior Member

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    I have a vague memory that a high percentage of drugs are used off label.


    If obvious gains are made is there any need for a trial? Obvious such as patients who were house bound getting back to a normal life and not a slight change in a score on a questionaire. I guess with a fluctuating condition this should be compared against a control group but there have been numerous studies with little sucess in such big gains. As the gains get smaller the need for better bigger trials increases.
     
  11. alex3619

    alex3619 Senior Member

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    Yes, taking the path of avoiding off label treatment means that nothing can be done to treat us. Even symptomatic relief is questionable as treatment depends on mechanisms and they have no proof that the mechanism for even basic symptoms is the same as that for which the drug was tested. Even drug testing is questionable though - it is often highly biased, usually on adult males, and now increasingly on adult males in Africa. Yet we generalize that to children and women.

    Even CBT/GET is unethical here because they don't use objective measures in those studies which appear to show some limited benefit (objective measures are usually found in studies with very minimal benefit, no benefit, or harm). Further they do not track most symptoms. Its also typically short term monitoring. Treating this like a drug means that CBT/GET would fail to be approved, and using it would be unethical at best.

    When a doctor prescribes things like aspirin, as user9876 alluded to, its often off-label treatment. Even aspirin also kills and disables many people - its not a totally safe drug.

    I would argue the single greatest risk, the greatest cause of harm, to ME and CFS patients, is not primarily the drugs. Its the profound ignorance that the vast majority of doctors have about the pathophysiology of ME and CFS. Even fairly safe drugs and treatments can be dangerous if you have no idea how they might affect the patient.
     
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  12. alex3619

    alex3619 Senior Member

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    Its an established principle of evidence based medicine that small gains mean big RCTs etc. as you state, but huge and obvious gains mean an RCT is often not even necessary - there are provisions for evidence status upgrading to account for this. The impact of the evidence is not just based on the type and size of study, but the effect size in outcomes.
     
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  13. orion

    orion Senior Member

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    It's weird isn't it.

    Many of the difficulties we face with the medical profession stem directly from the prescription system. It's inexplicable to me that any patient would support a system that deliberately restricts our freedom. It just doesn't make any sense. The term 'turkeys voting for Christmas' springs to mind.

    In my opinion, the prescription system is a gross infringement of our civil liberties, and could perhaps be challenged on human rights grounds. As far as I'm concerned, what I choose to put into my own body is nobody's business but my own. End of story.
     
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  14. Valentijn

    Valentijn Activity Level: 3

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    Please do explain how doctors prescribing Rituximab to ME patients is different than, for example, your own doctor prescribing Nuvigil for you, as you discussed in this recent post:
    Nuvigil is only FDA approved for narcolepsy, shift work sleep disorder, and with other therapy in sleep apnea. Yet you seem to be taking it to help you focus, improve your energy levels, and help with pain (ME symptoms). If it's not being used for actual narcolepsy or excessive daytime sleepiness caused by shift work, it is being prescribed off-label (hopefully your doctor did not mislead you about that). It has not been tested on ME/CFS patients, and there is no safety information about it for ME/CFS patients.

    How is your situation, as a very common example for ME patients, any different? Why is it okay to use prescription drugs off-label for symptom management, but not Rituximab, which might cause actual remission?
     
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  15. Firestormm

    Firestormm Guest

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    Aside from the article at the head of this thread, what has always intrigued me (and has been the missing link) with Rituximab is an answer to the question: Why should it work?

    Norway stumbled across Rituximab for ME. There was no aetiology discovered and no work since that I am aware of which indicates why or for whom this drug might prove most effective.

    I said before, off-label prescriptions are another matter. There is no list held centrally of drugs that GPs should consider for symptomatic relief of ME. GPs are able to use what they consider appropriate within reason.

    But is Rituximab being promoted as more than offering symptomatic relief? Isn't it being said that this drug gets to the heart of the condition? In that sense it seemed to me that Rituxmab might be equated with Ampligen and it's promoted benefits.

    If Kogelnik and others are willing to prescribe Rituximab to patients, my previous questions remain I think perfectly valid. I'd also like to know what his own hypothesis is regarding this drug and it's specific effects in regards to any aetiology he feels is most likely for ME.

    If Rituximab is delivering the kind of results we have seen in the small trial thus far from Norway - then the question remains as to why? This is an expensive drug - like Ampligen - this is not (thus far) a drug that appears to offer measurable benefit to everyone with this diagnosis. Why?

    Unless and until work is completed alongside any future blinded clinical trial that seeks to identify a viable hypothesis that indicates the kind of patient for whom this drug is most likely to benefit - I would argue it will be in the same boat as Ampligen.

    There is simply no evidence forthcoming that indicates why a doctor should prescribe and treat a patient with ME with Rituximab. There is no safety profile for Rituximab and ME. And those doctors who are treating patients with ME with Rituximab - how are they able to say that Rituximab (and not anything else) is leading to improvements? And of course - if a deterioration occurs - how do they or the patient know what is to blame?

    It is not enough - outside of for a patient - to see treatment with this drug leading purportedly to a physical improvement such as being able to walk further and more often. Unless greater study happens to ensure that we know how Rituximab is affecting patients with ME and why - all that will continue to happen is that this drug will be prescribed by private doctors in return for payment.

    Nothing wrong with that of course - so long as you don't mind being a guinea pig and have access to the money - but there is little chance - without further study - of this drug becoming available on the NHS for example. I want an aetiology advanced and established and I had hoped that Rituximab would offer this - for me it was the missing link from the work that has thus far been advanced.

    Even clinical trials will not reveal to us why Rituximab is seemingly so successful. I am pleased to hear that Kogelnik is provided as much information about what is known of the risk associated with Rituximab as he can - though we will not know what the safety profile is for people with our condition until long term studies occur. We cannot depend on anecdotal evidence in this and other respects - but hell we've been guinea pigs before - I would rather that this happened as part of a proper trial and study is all.
     
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  16. Valentijn

    Valentijn Activity Level: 3

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    It destroys B cells, which are generally associated with immune function. A study prompted by the Norwegian one took a look at B cell sub-populations in ME/CFS patients and found irregularities - basically too many naive B cells and not enough of a type of mature B cells. That study is posted and discussed here.

    Frankly, that's a helluva lot more information than is known about many FDA approved drugs, and the disorders that they're approved to be used upon.
     
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  17. Firestormm

    Firestormm Guest

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    Yep. I read it. It was a start but the authors themselves were very cautious (rightly so) and inconclusive. Indeed this study was looked at by the author of the OP article, who commented:

    I need to catch up on the comments - there have been quite a few more since I last looked it would seem.
     
  18. user9876

    user9876 Senior Member

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    I believe Fluge and Mella are doing more research looking at the immune system and ME to try to understand this. It should be said though that we don't really know why or how many drugs work. I've read a few papers around Rituximab and RA and they speculate over mechanism but have no definitive model. Fluge and Mella speculate that given the response patterns are similar it may be a similar mechanism.I was reading a paper about a different immune system treatment recently (not for ME) and although approved and quite expensive they said we don't know why it works.

    I don't see Rituximab as being that expensive a drug.

    Fluge and Mella do say that patients can get worse before they improve. Unlike ampligen Rituximab is a very well used and explored drug with quite a good safety record.Ampligen has a much more complex safety case in that the basis for the drug initially had a very bad safety record. Ampligen is changed from this basis and the claim is that it is now safe but the quality of the trial process appears poor hence a lack of trust in these claims.

    I think trials will only get some of the safety data anyway they will only tend to get short term data due to the length of the trial.

    How much do we need to know. More than other uses and diseases? I think you too high an expectation for the current abilities of medical science to understand how drugs actually work!

    The question for me is how big are the gains for those patients that improve some very big gains have been reported but I'm not sure what the spread is. The numbers in a trial should depend on the size of improvement.


    Anecdotal evidence of safety is absolutely critical. It and its systematic collection is what will give us knowledge of the long term safety of drugs.
     
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  19. Ecoclimber

    Ecoclimber Senior Member

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    I had something I had written up but it got lost...poof
    The main conjecture this whole argument is that Hall sets herself as the guardian along with a psych friend (which she met at a skeptic’s conference) as gatekeepers to bad medicine. Ignore them; they are nothing! They set themselves up as the 'gods' over the affairs of the medical profession acting as the sole judge and jury over the determinates of bad science. They author a two-bit hack job on a prestigious doctor who worked alongside Dr. Montoya at Stanford University with ME/CFS patients in a clinical trial center. We have U.S. government watchdogs. There are laws and procedures in place to protect the patient as well as the doctor. They certainly aren't the self-appointed watch dog regardless of what their delusional aspiration may be...(especially with a website rank of 72000)... I would be curious who they are funded by...perhaps pharmaceutical or disability insurance companies...hmmm.

    It is certain a two-bit hatchet job by Hall -- who I do not believe has any journalistic/investigative or research/educational background -- must be aspiring for a position as the health editor of the Washington Post. It is quite certain that Hall is clueless about this illness from the article and by her comments. Otherwise, she would have researched the 8000+ research articles on ME/CFS and at least known about the CCC and ICCC case definitions that clinicians use to diagnose and differentiate one patients groups from another which Hall is very oblivious to. Her condescending attitude toward ‘the malingers’ not knowing the background of some of these patients, says it all. In a majority of these cases, you have renowned doctors, academian professors, clinical psychologists, nurses, teachers, world renown Olympians, athletic champions and competitors, police, lawyers, airline pilots, scientific researchers stricken down with this illness after a post viral infection, Hall & her colleagues are clueless as to the seriousness of this illness and as well as to the scope of this disease within the general population. The cost to taxpayers of this illness is a staggering $29 billion. $7 million in funding is just to keep the lights on in the research departments while in comparison Aids Research receives $1Billion dollars for a smaller population.

    Kogelnik did absolutely nothing wrong. I know him. He is methodical and conducts a thorough medical work up on each patient before dispensing any type of medication. Patients have to fall within the CCC/ICCC definition and lab work and prior medical history is thorughly investigated. He is allowed to use off label drugs with informed consent under FDA guidelines. There is nothing illegal about it. Just as it is NOT illegal to offer Neurontin off label to ME/CFS patients. Doctors do it all the time. They use Rituxan for RA patients. They have been using it for a long time, it is a fairly safe drug. Dr. Hall, why don't you peddle your somatization theories somewhere else. Perhaps, undo the damage from the DSM Manual II stating that Homosexuality is an aberrant behavior and a serious mental disorder. What happened there! Did they become cured all of a sudden? How many diseases were mislabeled by the psych community still operating in the ‘dark ages’ and how many more do we have to contend with. We have newer scientific technologies that will bring real science to the field of medicine. Dr. Hall, focus instead on the real wackos in the field of medicine. The psych community with outdated psychobabble therapeutic models from Gestalt, Jungian, Rogerian, EFT, ESP, NLP, EMRD, Pass Life Regression, CBT, PACE, etc. and let us not forget frontal lobotomies and electric shock therapy! That is where you will find the real wacko practitioners selling Woo, Woo!

    Eco
    I will edit this later as I lost a large portion of what I wanted to say.
     
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  20. In Vitro Infidelium

    In Vitro Infidelium Guest

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    Isn’t your argument akin to saying that the crime of ‘Assault’ is not an issue because ‘Murder’ is so much worse ? It’s a false dichotomy and accepting it only takes discussion about M.E/CFS into an unresolvable conflict. “Neglect and the failure to carry out the necessary research” is perspective driven, it is not a universally acknowledge truth and making an argument that: “not recognising it as the ‘predominant’ ethical issue, is itself an ethical failure', when there is no adequate commonly accepted communicable evidence to support an assertion of “neglect and the failure to carry out the necessary research”, is perverse. Someone can not behave unethically if the data and context which underwrites the ethical paradigm is not available or communicable to them.

    “Neglect and the failure to carry out the necessary research” may be evident to patients (personally I think it’s a massive over simplification) but the rest of the world isn’t obliged to see things as we do. Berating people because they are not signed up to a M.E/CFS agenda, or disallowing the validity of their perspective of M.E/CFS because it doesn’t accord with ours is no way to develop engagement with those people. And without friendly engagement there is no way to have any chance of communicating a perspective which is amenable to our interests. In fact quite the opposite – it merely creates yet another group of ‘enemies’.
    Who is putting anyone where ? We have an illness or illnesses which are currently not amenable to being treated. Why should anyone outside the small circle of M.E/CFS affected people (we are tiny proportion of the world population) believe that medical research should have been committed to M.E/CFS rather than going elsewhere ? Where are the commanding scientific elements that could provide direction of research ? Research directions don’t evolve spontaneously, there has to be some principle to guide where research should be done. We have a difficult message to convey to the wider world and we can only do that by engaging with it on the terms that it demands, not how we wish it to be.
    Fluge and Mella's results do not suggest that that Rituximab may be a safe and effective treatment for a disease affecting many millions of people, and those researchers are explicit that Rituximab should not be considered a treatment at this stage. Treatment is a complete misdirection – the importance of Fluge and Mella's work was the indication that Rituximab could offer means to elicit details of what organic processes actually underly at least some cases of M.E/CFS.
    By dogma you appear to mean the scientific method and widely accepted norms of medical ethics. Of course you are free to make these judgements – but there is zero hope of actually being able to engage with the people who can actually effect the changes in political, research and clinical attitudes that would actually advance the interests of M.E/CFS affected people, on the basis of such judgements.

    IVI
     

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