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UK NHS provide rituximab for free for lupus patients. But not for ME/CFS patients. Why?

Discussion in 'Rituximab: News and Research' started by Hip, Dec 6, 2016.

  1. Hip

    Hip Senior Member

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    The UK National Health Service (NHS) provide rituximab treatment for free for qualifying systemic lupus erythematosus patients. See: Lupus - Treatment - NHS Choices.

    The NHS criteria for offering rituximab treatment to systemic lupus erythematosus patients is the following:


    The reason rituximab is offered for free to systemic lupus erythematosus patients, but not to ME/CFS patients, is presumably because of the large number of studies and evidence base demonstrating the efficacy of rituximab for lupus.

    The very first study I could find on the rituximab treatment of lupus was published in 2002, and immediately after that, there was an explosive growth across the world in the number of lupus rituximab studies being conducted.

    PubMed lists a total of 150 lupus rituximab studies and papers that have been published from 2002 to present. And in the first decade from 2002 to 2012, there were around 100 lupus rituximab studies published.

    I have listed a small selection of 37 lupus rituximab below, as a representative sample covering the decade from 2002 to 2012.


    By contrast, to my knowledge, there have only been three studies published on the rituximab treatment of ME/CFS so far, with a fourth underway, all of which were conducted by Oystein Fluge and Olav Mella in Norway. These 4 ME/CFS studies are also listed below. When the fourth study is published, these 4 studies will also span a time period of around a decade.

    But note the huge difference in the number of studies, and the lack of explosive growth or global interest in replicating the ME/CFS rituximab studies. In the case of lupus, there were around 100 lupus rituximab studies published globally in the first decade. But for a similar decade timespan, there have only been 4 ME/CFS rituximab studies, and all from the same country of Norway, by the same authors, with no replication studies in other countries.

    Why is this? Why the explosive interest in the lupus rituximab studies, but so much less interest in the ME/CFS rituximab studies?

    Are ME/CFS patients once again being seen as second class citizens, sent to the back of queue for research and treatment? Or are there legitimate reasons for this slow uptake and lack of funding for ME/CFS rituximab research?




     
    Last edited: Dec 6, 2016
  2. SuzieSam

    SuzieSam Constant companion

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    It's completely maddening. I think there's definitely an anti-ME bias, but it's complicated by the fact that there are clear blood tests to define Lupus, and not ME. Unless they only give Rituximab to those ME sufferers who show over-abundance of B cells or specific markers in their B cells?

    How can they clearly define who to give it to, when ME, "Chronic Fatigue", CFIDS, is such a huge catch-all term?

    Aren't we always told there's no test for it?

    It's a drug with dangerous side effects - desperate as we are, a lot of us would try it, I'm sure. But please tell me - what test would show it could work for you. Or me?

    I'm so brain dead, please pardon my lack of scientific understanding right now.
     
  3. Skippa

    Skippa Anti-BS

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    Are doctors allowed to prescribe Rituximab off label if they wish? Or does it somehow get "blocked" at acquisition lebel?
     
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  4. taniaaust1

    taniaaust1

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    Lack of ME/CFS studies I personally put down it being caused through the damage the psych field has done to our illness and the governments lack of willingness to give much money for ME/CFS research. We should be using examples such as this at why governments should be putting A LOT of money into our research (and not into more psych stuff either).

    They just need to use the stricter ME/CFS definitions eg ME international or the Canadian and choose the sicker patients and I don't see why there should be an issue doing this research on us. They wont know who and who it don't work best on with us UNLESS they do more studies.
     
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  5. Skippa

    Skippa Anti-BS

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    'Cos it costs a fck ton of $$
     
  6. roller

    roller wiggle jiggle

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    dont be angry @Skippa
    perhaps it would do much harm.
    for ppl with tinnitus, crawlings, buzzes and so...
     
  7. alex3619

    alex3619 Senior Member

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    Numbers of studies and lack of funding are two of the issues. The third is the lack of a clear diagnostic test for ME. This may change soon. There is however clear institutional bias in the UK, but then again there are all sorts of biases throughout medicine. We need that phase 3 trial, we need more funding, we need a diagnostic test that is has at least 95% for both specificity and sensitivity. It would also help if we had a test that identified the subgroup most likely to respond. There are ME researchers working toward these things right now.
     
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  8. TrixieStix

    TrixieStix Senior Member

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    Yes it's been stated a few times very recently by ME/CFS researchers that it is not yet appropriate to be giving Rituximab to ME/CFS patients outside studies/trials.
     
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  9. TrixieStix

    TrixieStix Senior Member

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    Dr. Nancy Klimas talked abt Rituximab in this recent interview uploaded
    December 2nd.






    And Dr. Fluge also spoke about it in his presentation (video) at the October Swedish me/cfs conference.
     
  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Dear @Hip,
    Since I was responsible for starting the use of rituximab in lupus and the spate of studies and I am as much as anyone responsible for the absence of rituximab studies at least in the UK, I am probably in a good position to answer.

    The large number of reported studies in lupus actually has nothing to do with it. Nor has funding much. The only large grant-funded studies in lupus did not give conclusive results. The vast majority of studies, including mine, had no funding. We just got on with it. Maria Leandro did the first study, as a visitor on no pay.

    The reason lupus patients are treated is that the patients involved are mostly young women who are considered highly likely to die of their disease within a year, if not sooner. Under those conditions it is very hard not to try treatments that have shown dramatic improvement not just in symptoms but in biomarkers that make sense. It is also easy to treat a disease known to be due to B cells with B cell depletion. Moreover, even within lupus we have identified responder markers related to different sorts of antibodies. None of these factors apply in ME. Even the autoantibody studies we now have are hard to interpret.

    There may be biased attitudes but I think it is a mistake to blame these when there are perfectly good reasons why the situations might be different.

    It may be interesting to note that although rituximab studies in RA were set up with robust design, with adequate funding and led to a license for treatment, in lupus most of the studies are small and inconclusive with the result that there is no license in lupus. The flurry of activity is actually a mess, not to be encouraged.
     
  11. Hip

    Hip Senior Member

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    Thank you @Jonathan Edwards for clarifying that. I was hoping you would shed some light on this.

    So you are saying that in the case of lupus, the reasons for the relatively rapid introduction of rituximab treatment are:

    (1) There was already a good understanding of the pathophysiology of the disease.
    (2) There was a clearcut understanding of the mechanism by which rituximab would address and ameliorate that pathophysiology.
    (3) There were biomarkers that indicate in advance which lupus patients are likely to respond to rituximab (so that this expensive treatment is only given to those patients it will likely help).
    (4) There were biomarkers which objectively indicate the improvements in health obtained from rituximab treatment (so you did not just have to rely on subjective accounts of symptom improvements).
    (5) A pressing situation in which if rituximab treatment is not provided very quickly, the patient may well die.

    Hopefully if Fluge and Mella continue to make inroads into understanding ME/CFS pathophysiology, this may then lead to points (1) to (4) applying to ME/CFS as well.


    In the case that the Fluge and Mella phase III study results are positive when published in 2018, do you think that NICE will pay attention to these, and consider making rituximab available to UK ME/CFS patients? Or will it require replication of these results by a British team before NICE take significant notice?


    Was the 2002 lupus study by yourself, Jo Cambridge, and others the first paper that opened the field of rituximab treatment for lupus, by the way? Any idea how many years it took for the NHS to pick up on this rituximab treatment for lupus, after this 2002 paper was published? In other words, what was the time lag between the first published lupus results, and the NHS incorporating rituximab treatment for lupus within the NHS guidelines.
     
  12. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    If the Norwegian study is clearly positive I think the UK approach to ME will change out of all recognition. Nobody will be bothered with psychological approaches. Physicians will only be interested in the biological side. As to how soon rituximab might become an option on the NHS I think it is difficult to say but some centres will want to offer it as part of further research at least.

    Our 2002 study was the first in lupus, just as our 1999 study was the first in RA. Once we had presented our findings to the rheumatology world, and even before full publication, there was interest from other lupus physicians, particularly the renal physicians dealing with renal lupus. Off label treatment has always been common for lupus so anything interesting tends to get taken up and used pretty much straight away. The NICE guidelines do not matter much because hospitals always find money for lupus management if it is needed. Managing lupus is so expensive anyway that rituximab probably saved thousands on kidney transplants from the word go. The situation would be different for ME if a useful effect is confirmed but there is still likely to be a rapid interest in using it.
     
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  13. BurnA

    BurnA Senior Member

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    Is the underlying mechanism in the treatment of lupus with rituximab understood? Apart from the b cell depletion, is their an identified antibody in lupus. Sorry, I don't know much about that disease. Just wondering if the rituximab work lead to more insights into the disease.

    Would it be correct to say RA was well understood when you performed the rituximab study or was there still a large element of unknown? Again, curious if it lead to further understanding of the disease and if it shaped future research. Tks.
     
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  14. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    There are a shedload of identified antibodies in lupus, which is what makes it unique. Most autoimmune diseases are like mill wheels. Lupus is like a Swiss watch with an antibody at each cog. You have antiDNA, anti-Sm, Anti-RNP, anti-platelet, anti-red cell, anti-leucocyte, anti-Ro, anti-La, anti-Jo-1, anti-thyroid peroxidase, anti-phospholipid and I could go on.

    Nobody has ever doubted that lupus was due to autoantibodies because it has the classic appearance of an antibody-antigen immune complex disease. You can find the complexes in the kidney and in the brain.

    But when I treated rheumatoid with rituximab virtually everyone thought the inflammation was due to T cells. What my students Barbara Bröker, Vikki Abrahams, Ajay Bhatia and Richard Lee were able to show was that there are in fact two quite different sorts of immune complex mediated inflammation and the second one is the pattern of RA. In lupus you actually get both.Big complexes fur up kidney and brain blood vessels and settle out in skin to give a rash. You can find them stuck there. Small complexes, on the other hand tickle up macrophages to make TNF and because they do not actually accumulate anywhere you cannot find them concentrated in the tissues. All you find are the effects of the TNF. It all centres around a receptor called CD16.

    Having worked that out we worked out that getting rid of antibodies in RA was actually worth doing something everyone else thought was a waste of time. We proved them wrong! Over the last fifteen years the T cell interest has very gradually faded away, although old vested interests die hard. I think it probably fair to say that all immunological interest in RA now focuses on B cells - even B cells that do not exist; the fashionistas will always decorate the truth with fairy tales!

    Put another way, until we tried rituximab in RA everyone was barking up the wrong tree. Now they are at least barking at the right tree. I was happy I had climbed far enough up to see what was going on but decided to come home for tea.
     
    Last edited: Dec 8, 2016
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  15. Jo Best

    Jo Best Senior Member

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  16. Gingergrrl

    Gingergrrl Senior Member

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    @Jonathan Edwards Could RTX work for someone who had many different autoantibodies (in my case now eleven) even if they did not match with a known disease pattern such as lupus?

    Would the autoantibodies (for me or anyone in my situation) require a disease that has an official name in 2016, or could RTX wipe them out regardless?

    I have had incredible improvements from IVIG and about to start six months of high dose IVIG next week. We are hoping this will be enough and RTX will not be needed but no way to predict. We are almost 100% certain that ME/CFS is not my diagnosis vs. all of these autoantibodies causing chaos to my system.
     
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  17. justy

    justy Donate Advocate Demonstrate

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    OT - so happy for you - I know how hard you have worked to find answers for yourself, I hope this doesn't mean you are going to leave us? apart from enjoying your company I think that you shoe how easy it is for people to be misdiagnosed - in the UK we don't have access to the kind of testing you have had done. How would I ever know if I also had multiple autoantibodies when we only get tested for such a narrow amount of things over here?

    sending you best wishes.
     
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  18. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Rituximab is helpful in most of the autoantibody-associated syndromes known but not all. So for a picture that does not fit a specific diagnosis one cannot predict but there is a reasonable chance of benefit if the autoantibodies are responsible for the symptoms.
     
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  19. Gingergrrl

    Gingergrrl Senior Member

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    Thank you @justy and I plan to create a new thread in the next few weeks to update everyone re: my progress with IVIG. I don't want to do it here b/c it is too long and will take this thread off track. But I am not leaving PR and appreciate the kind words (and if I do leave PR in the future, I would let the board know and promise not to disappear and worry everyone). I had to take some time off at the end of Oct and put myself on the burn-out bench. I'm only now posting sporadically b/c dealing with a personal situation that is taking up most of my time (in addition to the IVIG and other medical research/treatments).

    I couldn't agree more and I suspect that there are hundreds of different diagnoses represented here on PR (that share both overlapping causes and symptoms). No one truly knows what ME/CFS is (IMO of course) so maybe I still fit one of the sub-groups if there is an Autoimmune/MCAS/POTS/ Muscle Weakness subgroup but I do not have fatigue, PEM, flu-like symptoms, cognitive, or sleep issues and overall, it just does not feel like the right match.

    As far as the autoantibodies, the test that I did is not actually even available here in the US and is a test through Cell Trend Lab in Germany. So I had to send a blood sample to the lab in Germany from the US and then I discussed the results with my doctor here. So you could absolutely send a blood sample to Cell Trend from the UK if you are interested and we have several threads on this topic (most started by Lolinda if you do a search).

    Seven of my autoantibodies were from the Cell Trend tests (the beta adrenergic ones showing that I have "Autoimmune POTS" and the anti-muscarinic/cholinergic ones which are affecting my breathing and muscle strength). Then I also have the N-type calcium channel auto-antibody, the GAD65 auto-antibody, and the two Hashimoto's auto-antibodies. We suspect I have even more if we were to do more testing but the treatment right now would still be the same (high dose IVIG and possibly later RTX).

    In the briefest nutshell, I went from 24 grams (July-Sept) to 55 grams (Oct & Nov) and later this week (Dec) will be doing 82 grams (Gamunex) in a 3-day split dose. I will be doing the high dose IVIG for the next six months. It is without question the best treatment I have done in my entire illness. I will explain all of it when I create an update post in the next few weeks. The key for me is doing a VERY slow infusion speed b/c of my MCAS.

    Thank you and likewise! I promise I am not leaving PR, I just don't have the time at present to post due to a personal issue and my research/treatment. But in the future, I will share everything that I have learned and really hoping that my experiments will pay off and help others. Am also happy to chat via PM but I get a lot of PM's and apologize in advance that I am often slow to reply.
     
    Last edited: Dec 12, 2016
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  20. Gingergrrl

    Gingergrrl Senior Member

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    @Jonathan Edwards Thank you so much for your prompt reply and it was exactly what I was hoping you would say! We feel that I have an "autoantibody associated syndrome" (to use your term, which I really like!) and that it does not fit with a known disease such as lupus and so far is not a paraneoplastic syndrome b/c no cancer has been found.

    It started off viral but at some point shifted to autoimmune. I am having amazing improvements from the IVIG (just the bottom of the autoimmune dose for two months) so this month am increasing to the middle of the AI dose and if it goes well, will increase to the top of the AI dose next year. My doctor felt that if I make a significant improvement from IVIG, it means I am a good candidate for RTX to wipe out the autoantibodies at the production level (vs. temporarily knocking them down with IVIG only to have them return).

    Both of my doctors said it is within the realm of possibility that high dose IVIG alone could lead to a permanent recovery all the way to the flip-side that I could do RTX and then the new B-Cells could still re-grow with the same auto-antibodies. Neither of my doctors can predict what will happen and no one is making false promises. But based on my test results and improvements from IVIG thus far, we think I am a good candidate for RTX even though I do not have an autoimmune illness with a specific name like "Lupus" etc.

    It sounds like, from your reply, that even without a specific diagnosis, that RTX could help if autoantibodies are the cause of my symptoms which we believe they are. Am so glad that I asked you this question. Now whether my insurance will approve RTX and whether I will be allergic to it is another story! But I expected to be allergic to IVIG, and I am not, so you never know.

    Thanks again!
     
    Last edited: Dec 12, 2016
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