Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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Rituximab and ME/CFS in the UK - MEA update

Discussion in 'General ME/CFS Discussion' started by charles shepherd, May 23, 2016.

  1. charles shepherd

    charles shepherd Senior Member

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  2. jaybee00

    jaybee00

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    Again with the big discrepancy between the anecdotal accounts and the published reports......
     
  3. A.B.

    A.B. Senior Member

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    I wonder if the people taking Rituximab outside of the clinical trial are the severely affected? Sounds probable. Fluge and Mella didn't have good results with severely affected either.
     
  4. jaybee00

    jaybee00

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    looks like the anecdotal data is issue is discussed in the Amolak Bansal thread....
     
  5. charles shepherd

    charles shepherd Senior Member

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    As already discussed on the Sussex Research and Management meeting thread:

    I am only aware of anecdotal cases outside Norway where there has not been a response to rituximab and it would, of course, be interesting to know about instances where there has been a positive response

    Dr Bansal did not quote any numbers and we were left with the impression that, quite sensibly, the when, where and how of a UK trial is the subject of on-going discussion

    I did not get the impression that he felt that there were any robust clinical or biolological markers that could (in the present state of knowledge) separate people who were more likely to respond to rituximab and those who were less likely to respond

    The anecdotal responses seem cover a wide range of disease severity.

    Here are two that have been posted on PR. There are others…..

    (1) The Open Medicine Clinic is providing Rituxan for patients all over the world. I just finished my treatment with very little/no response. Very disappointing, but I felt I had to give it a try. It is very expensive, but there is a pretty good program to help with medication cost if your income is at a certain level and you can prove your insurance won't cover it. Even with the medicine free, the visit is $1500 to $2000 each (x6) plus hundreds of dollars of blood tests. I know there are certain infections they test for before you can go through it, I don't know if Lyme is one of them.


    (2) swollen throat


    Not Sore. swollen. Maybe swollen bfore rtxn but much worse after. , it's been 8 months on rtxn and over two months since last infusion.

    Causing (worse) apnea. Had a home sleep study and apnea is significant.

    Anyone else? Any ideas?

    gargle with salt water helps the swollen throat a bit.

    This seems to help as well:

    http://www.1cascade.com/ProductInfo.aspx?productid=4333

    Will try this next:

    http://www.1cascade.com/ProductInfo.aspx?productid=2726

    "Red root is a lymphatic stimulant useful in tonsilitis, sore throats, swollen lymph nodes and fluid-filled cysts. "

    Any problems with these? If echinacea stimulates immune sys, bad idea aftr rtxn?


    bad sleep

    6/12
    Pre-rituxan I used to usually sleep through the night, at least the majority of the time, even if not the same quality of sleep as I got pre-CFS. I haven't slept through the night once in the 5.5 months since RituxanIt's getting to be a pretty bad situation. I wake up a lot, and often can't get back to sleep after only 4 hours. I'm really sleepy during the day. When I don't actually wake up, I almost always toss and turn and sort of "half wake up" all the time.

    D Ribose didn't used to affect my sleep, but since Rituxan, if I take it during the day (last dose way before bed time) or even in AM only, I lay in bed in a kind of half sleep state where I can't get all the way to sleep.

    I had mild sleep apnea before Rituxan, and tha'ts gotten worse. But I think there is something more going on here as well given the "half sleep" (worsened by sugar).

    There was a change immediately after Rituxan.

    9/12
    (update- been 8 mnths and slp a bit better BC of no sugar/carbs for 6hrs bfr bed). But still nt good. Apnea worse.

    Curious if anyone else has noticed this?

    CFS also wrse

    I can't talk. Can't type/text enough to communicate. Haven't had a conversation with someone in 8 months...
     
    Plum likes this.
  6. charles shepherd

    charles shepherd Senior Member

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    Additional info now posted on the MEA website re the MEpedia entry on rituximab:

    Patients might be interested to know that a page is being maintained on MEpedia about Rituximab and what we know about its risks, availability and the mixed picture from the studies done so far.

    Professor Edwards has contributed to the page.

    MEpedia is a wiki so anyone can click Edit improve the page (just like Wikipedia), adding new articles, studies etc and I encourage patients and professionals to consider doing that so we have a single place to collate what is known.

    http://me-pedia.org/wiki/Rituximab

    It’s vital patients have a full picture of what is happening, especially with a drug with known risks and where efficacy is muddy and we do not have any way to identify any subgroup for treatment with it.
     
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  7. snowathlete

    snowathlete

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    Thing is these anecdotal reports from the US are just that. They haven't been conducted under trial conditions, and we don't know how many patients we are talking about it what kind of diagnosis they have. Maybe those considering a UK trial have seen more factual details, but it doesn't seem a reason not toco duct a UK trial to me from what little I have heard.
     
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  8. barbc56

    barbc56 Senior Member

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    Would it make sense to wait until the Norwegian trial is over before starting other studies? Since that study is the first (?), whatever the outcome, we don't know the study design. I would think these factors would determine what type of study protocols are a best use of resources for future studies.

    Then again, maybe there are reasons to start other studies, that I'm not aware of, since others have already started.

    I have no idea what the pros and cons are of running other studies at the same time.

    Anyone?

    Edit

    I didn't see the other posts before I responded. Something about all the ancedotal reports and speculation niggles negatively in the back of my mind. But I can't quite sort it out as far as why. Maybe the back story would explain this?
     
    Last edited: May 23, 2016
  9. charles shepherd

    charles shepherd Senior Member

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    Just to be clear: Dr Bansal was not saying that there should not be a UK clinical trial on the basis of adverse or disappointing anecdotal reports.

    Clinical trials should, of course, be providing the 'Gold Standard' information that is required when it comes to making important decisions as to whether a drug (or a behavioural) treatment is safe and effective and whether something like rituximab should then be licensed for use in ME/CFS (and recommended for use by NICE here in the UK)

    And normally they do

    But there are exceptions……..

    In the case of ME/CFS, the conflicting evidence from clinical trials and the 'patient evidence' in relation to CBT and GET immediately springs to mind.

    And there are other instances where clinical trials have dismissed forms of treatment in ME/CFS where the 'patient evidence' indicates that they could be safe and effective (e.g. vitamin B12)

    So doctors who are planning clinical trials also have to take notice of anectodatal patient evidence, as as well as anecdotal evidence from clinicians, when deciding how to move forward with a clinical trial that is going to provide further evidence on safety and efficacy in the case of a very costly treatment such as rituximab - where there are also issues and concerns relating to both short term and long term adverse effects

    I take the view (along with many of my clinical colleagues) that in our current state of knowledge the use of rituximab in ME/CFS should normally be restricted to properly organised clinical trials. This is partly because rituximab is a drug that has the potential to cause very serious side-effects. So I don't think it should be used outside clinical trials until we have further information on safety, efficacy and we know more about which patients might or might not respond

    However, out in the real world, patients in the US are being prescribed rituximab outside clinical trials and they are reporting their experiences to clinicians and on the internet - some of which are very disappointing or concerning

    All that was being said at the meeting was that this 'patient evidence' also has to be noted and discussed.

    It would be negligent not to do so.

    The MEA continues to believe that there should be high quality clinical trials of rituximab taking place outside Norway to see if other groups can replicate the findings relating to safety and efficacy (as well as identifying sub-groups that may respond better/worse than others)

    Consequently, our offer to provide around £60,000 (possibly more) to help fund a clinical trial of rituximab here in the UK remains on the table
     
  10. msf

    msf Senior Member

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    I wonder if any of the medically-minded would like to suggest how Ritux could make someone´s sleep worse? Here´s my guess: Ritux can cause IgA levels to drop, allowing more translocation of LPS from the gut and thereby causing more inflammation in the body, affecting the HPA.
     
  11. charles shepherd

    charles shepherd Senior Member

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    Waiting for the results of the phase 3 clinical trial in Norway - which should appear in late 2017 - is one option that was debated in our last MEA statement on Rituximab:

    http://www.meassociation.org.uk/201...lable-for-a-clinical-trial-12-september-2015/

    This would, of course, mean that a UK trial would not probably start till some point in 2018, we might then be waiting 2 or 3 years, or longer for these results - taking us into 2020 or beyond……

    Remember, here in the UK, the licensing authorities and NICE will want to see robust evidence of both efficacy and safety in ME/CFS in several large and high quality independent clinical trials before this drug is approved for use in ME/CFS
     
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  12. barbc56

    barbc56 Senior Member

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    This clarifies what could happen. I must have skimmed over this part and missed the implications. Looks like I need to reread the blog.

    Edit. Cross posted with Doctor’s Shepherd. Thanks, that helped.
     
  13. BurnA

    BurnA Senior Member

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    Why would they change their standards all of a sudden ?
     
  14. Valentijn

    Valentijn Senior Member

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    Actually it sounds like he is precisely saying that further trials should not be held due to anecdotal reports, based on what you have reported of what he has said: "Consequently, questions are now being asked as to how a UK trial could/should proceed and whether this is the right time to commence a UK trial."

    If you're going to stall a trial for years due to anecdotal reports, will the trial only be considered again when anecdotal reports have improved? o_O This makes no sense, and it sounds like Dr Bansal is suggesting shelving the possibility of a Rituximab trial, as a result of elevating selective anecdotal reports over carefully collected and reported trial data.

    Several? Two phase III trials are expected, at most. One is underway in Norway. And the years that such a trial will take to conduct are a reason to start sooner, not later.

    Or is the MEA just looking for excuses to not conduct a Rituximab trial, until the results can be predicted with complete certainty?
     
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  15. BurnA

    BurnA Senior Member

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    That's what is appears like.
    If there are patients who can benefit from RTX surely there is a responsibility to perform a trial sooner rather than later ?

    Of course we would all like to know how RTX works and on whom, but the priority should be proving if it works or not.

    To wait for the results of the phase III trial from Norway would be to ignore their phase II trials completely.
     
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  16. charles shepherd

    charles shepherd Senior Member

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    Sorry - not with you here

    This is how things work in the UK……

    Although you could, of course, argue that NICE made a mistake in approving CBT and GET for everyone with mild or moderate ME/CFS….
     
    ukxmrv likes this.
  17. charles shepherd

    charles shepherd Senior Member

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    1 As I have already tried to explain, Dr Bansal was NOT saying that a UK clinical trial should be deferred on the basis some disappointing anecdotal reports from people who have been treated in America outside a clinical trial. He was saying that these reports have to be built into the overall discussion as to when. where, and if a UK clinical trial is going to take place. Results from well organised randomised controlled trials are, of course, the Gold Standard in assessing new forms of treatment. But evidence from patients and clinicians does have to be taken into account when you are planning a trial with a drug like this that is both expensive and has the potential to cause serious adverse effects in both the short and long term.

    2 There is a phase 3 trial in progress in Norway with results expected in the summer of 2017 but I am not aware of any other phase 3 trials in progress. Phase 3 clinical trials normally involve large numbers of patients and are therefore very costly to set up, especially when they involve an expensive drug like rituximab. So it does not look as though the proposed UK trial will have phase 3 status. As you may have seen, I have brought this matter to the attention of the Board of the CMRC in the hope that we might find a group that wants to submit an application to the MRC for a phase 3 trial - without success so far

    3 The MEA is not trying to set up a clinical trial and we are not trying to raise the full costs of funding one. Our position has remained the same for the past three years: We are keen to see a clinical trial of rituximab take place here in the UK and are willing to provide around £60,000 from our Ramsay Research Fund to help fund a trial - if an application from a suitable clinical trials group is received. Dr Bansal and Professor Edwards - who are advising on a UK trial - are both aware that this funding is there if/when a protocol etc is developed and they want to apply for some additional help with funding
     
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  18. Kati

    Kati Patient in training

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    @charles shepherd Regarding costs of dr visit for Rituximab infusions, the amount is very inflated. I would suggest to verify your sources. I do not want to start a war but it would be fair to ask more than one person.

    The costs related to Rituximab infusion, other than the drug itself involves the necessary nursing care and the labs in order for it to be infused safely. Only a few labs are necessary between infusions.

    While you disagree with using Rituxan outside clinical trials, you need to understand that patients are desperate for medical care, the competent kind. This is showing by the fact that patients are willing to travel from all around the world in order to receive said drug. Is it unethical to give patient a chance at improvement in the present political climate that ME is in, when current medical care is 'get out of my office' ?

    Rituximab trials, unfortunately, take years to generate results. In fact the next set of results is expected in 2017, maybe 2018. What are patients to do in the meantime? Some are not willing to wait that long. Some are too sick to wait that long. And quite honestly, physicians who treat us, our ME experts, all have treatments outside the clinical trial evidence. Antibotics? Anti-virals? GC-Maf? imunovir? Ampligen? There are no approved drugs for ME, after all. But our ME experts do the best they can with the knowledge they have. I am thankful for each one of them.
     
  19. charles shepherd

    charles shepherd Senior Member

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    [

    Of course we would all like to know how RTX works and on whom, but the priority should be proving if it works or not.

    Yes, doctors do not have to wait to know the cause of a disease before trying out various forms of treatment

    This is a two way process:

    Discovering the cause of a disease can obviously lead to effective forms of treatment

    But trying out speculative forms of treatment can sometimes help to provide important information about the cause of a disease
     
    BurnA likes this.
  20. snowathlete

    snowathlete

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    If the anecdotal information is simply the little that is already in the public domain; a few apparent patients with me/cfs who have had rituxan without it working in the US, conducted by one group, then I am not sure I agree that it should be taken into consideration when deciding when, where and if to conduct a formal trial in the UK.

    If the information was more compelling then I could perhaps agree with that view a bit more, but it seems very weak reasoning to me. I mean, we had six? patients in the original positive pilot study in Norway and that was rightly considered too small to draw any conclusions from and that was a formal trial. So even if we had a similar number in the US who reported the opposite in a trial that again would not be sufficient to draw any conclusions, it would at best create caution and uncertainty as it conflicts with reports from Norway...but we aren't even talking about that. We're talking - so far as I know - about a few patients outside of a trial, who had the drug given by the same group in the US and told people on the net that it didn't work for them. It's really no evidence at all, in my opinion.

    Given patients are in need of a treatment, there is some formal evidence to suggest rituxan *might* work, and that proper formal trials take time to conduct, before which any potential treatment will not be possible in the UK, I'm disappointed at how long it is taking to get going. I know it isn't easy, it has to be done properly, and there are a lot of obstacles to overcome, but that just makes it more annoying that such weak evidence being discussed is causing serious questions as to when and if a trial should be conducted in the UK.
     
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