Would you care to elaborate on what funding you think they had?
Rituximab Phase III - Negative result
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Unfortunately they have stopped giving ME/CFS patients infusions here due to critique from public health officials. I will not be able to do it at this point.
Very saddened because at least I had the option, now I don't anymore.
It might turn out to be for the best in the long term. It seems clear that RTX benefits some people, but it isn't clear yet who and why. Hopefully this will be unpicked, and you may then have the opportunity to find out whether you're a good candidate for it. (This is probably why we haven't heard anything more from the Norwegian research team – they'll be doing their best to understand their results as fully as they can.)
If you're not likely to benefit from the drug, then at least you won't be exposed to any possible risks unnecessarily. If they are able to profile likely responders clearly enough and you're among them, there's no reason to think that there won't be further opportunities in the future.
If people improved, they improved...whether temporary or not. I've had mini-remissions and ongoing crashes. Not sure how other people experience this illness, but when I feel better...I know it. I think we have to wait for publication to understand measures and methodology. They are also working on cyclophosphamide, doesn't that impact T-cells? There has been a long wait for publication, but I'm hopeful that they are doing a strong analysis and will provide insight into who will best benefit from Rituxan. My guess is that when the paper is published, there will be valuable insights that benefit the progress of research into ME. If there is a whole subgroup that can be helped, that could still equate to potential treatment for millions of people. BTW - isn't it common in disease groups that some treatments work for some, but not all?
Gingergrrl
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I was not part of any study but was not tested for a CD20 marker prior to starting Rituximab.
I agree! Even if only 5-10 people in the study got better, I would want to know why. I would want further testing and study on those patients vs. deciding that no one on earth can be helped by this drug (I am not addressing this to you, just my thoughts in general).
Wow, thanks for explaining that and I was not familiar with it at all before this thread.
I agree.
I had posted these questions about CD20 and received several responses that made me dig a little deeper about my question. Mayo Clinic’s lab has this to say about CD20 testing - https://www.mayomedicallaboratories.com/test-catalog/Clinical and Interpretive/89584
Useful For
Evaluation of CD19 deficiency in patients with a suspected CD19 deficiency (humoral immunodeficiency)
Confirming complete absence of B cells in suspected primary humoral immunodeficiencies using both CD19 and CD20 markers.
Assessing therapeutic B-cell depletion quantitatively (absolute counts of cells/mcL) in any clinical context, including malignancies, autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and membranous glomerulonephritis among others, and treatment or prevention of acute humoral rejection in positive crossmatch renal transplant recipients
This test is not useful for assessing whether B cells express the target molecule (CD20) in the context of initiating therapeutic monoclonal anti-CD20 antibody therapy (rituximab, ofatumumab, and tositumomab) for any of the hematological malignancies, or in other clinical contexts, such as autoimmunity, instead order CEE20 / CD20 Cell Expression Evaluation, Varies. (Note - I added bolding to this section to highlight it.)
Clinical Information
CD20 is a protein that is expressed on the surface of B cells, starting at the pre-B cell stage and also on mature B cells in the bone marrow and in the periphery. CD20 is not expressed on hematopoietic stem cells, pro-B cells, or normal plasma cells.(1) Plasmablasts and stimulated plasma cells may express CD20.(2) CD20 is generally coexpressed on B cells with CD19, another B-cell differentiation marker. CD20 appears to play a role in B-cell development, differentiation, B-cell receptor (BCR) signaling, and cell-cycle initiation events.(3) CD20 is not shed from the surface of B cells and does not internalize on binding with anti-CD20 antibody, nor is it typically present as a soluble free antigen in circulation.(3) Certain primary humoral immunodeficiencies, such as X-linked agammaglobulinemia and autosomal recessive agammaglobulinemia, are characterized by a complete absence or profound reduction of peripheral B cells, expressing both CD20 and CD19 (another B-cell differentiation marker).
Mutations in the CD19 gene have been shown to be associated with a primary humoral immunodeficiency, sometimes classified as common variable immunodeficiency (CVID).(4) This defect accounts for less than 1% to 2% of CVID patients and appears to be inherited as an autosomal recessive defect.(4) Since these patients have normal numbers of B cells with absent CD19 expression on the cell surface (4), CD20 can be used as a marker to help identify these patients.
A contrasting situation exists for patients receiving rituximab, ofatumumab, and other anti-CD20 monoclonal antibodies that are used to treat certain cancers, autoimmune diseases, or for B-cell depletion to prevent humoral rejection in positive crossmatch renal transplantation. These agents block available CD20-binding sites and, therefore, the antibody used for this flow cytometric assay cannot recognize the CD20 molecule on B cells. The concomitant use of the CD19 marker provides information on the extent of B-cell depletion when using this particular treatment strategy.
The absolute counts of lymphocyte subsets are known to be influenced by a variety of biological factors, including hormones, the environment, and temperature. The studies on diurnal (circadian) variation in lymphocyte counts have demonstrated progressive increase in CD4 T-cell count throughout the day, while CD8 T cells and CD19+ B cells increase between 8:30 am and noon, with no change between noon and afternoon. Natural killer cell counts, on the other hand, are constant throughout the day.(5) Circadian variations in circulating T-cell counts have been shown to be negatively correlated with plasma cortisol concentration.(6-8) In fact, cortisol and catecholamine concentrations control distribution and, therefore, numbers of naive versus effector CD4 and CD8 T cells.(6) It is generally accepted that lower CD4 T-cell counts are seen in the morning compared with the evening (9), and during summer compared to winter.(10) These data, therefore, indicate that timing and consistency in timing of blood collection is critical when serially monitoring patients for lymphocyte subsets. (Note - I added bolding to this section to highlight it.)
Based on the first section highlighted in the quote above, it would lead me to think that CD20 may not be a test that is routinely ordered for ME/CFS patients who are given Rituximab. So, I am now wondering if there could be another marker, test, or combination of tests that might give some guidance into who may or may not receive some benefit from this drug. My search will continue. *Edit - I do note that the Mayo Lab refers to two other CD20 tests that could be ordered, so perhaps my question about CD20 testing may still be open for further review?
The second part of the quote from Mayo Labs that I highlighted above was done because I thought it provided some interesting info. about testing of T-cells, B-cells and NK Cell’s related to circadian timing. I don’t want to de-rail this thread with this bit of information, but I thought it was interesting to at least note the variables that can result from blood testing when not carefully controlled and replicated.
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In doing some more research about Rituximab, I came across this interview between De. Judy Mikovits and two German doctors regarding the use of this drug in ME/CFS patients. This information is not being posted for people to use it to bash Dr. Mikovits or XMRV, so please refrain from venting any negative feelings you may have about those topics.
I just wanted to share the studies and findings discussed in this interview because it seemed to cover some possible answers as to why this drug may only work in a subset of ME/CFS patients, Note that this interview appears to have been published on Youtube in 2015. Dr. Mikovits states that she was in contact with the Norwegian doctors (Fluge and Mella) back in 2010 while they were investigating how this drug might or might not work in ME/CFS patients.
I think the interview was worth my time to watch in its entirety to get a better understanding about the science behind the use (or trial) of drugs like rituximab, ampligen or even anti-retrovirals in illnesses such as ME/CFS. I believe that others might also find what is being discussed in this interview to be very interesting.
Since it appears that this video has had under 500 views, it may not have been seen or even watched in its entirety by many in the ME/CFS community. At minute marker 3:24 - 7:26, there is a discussion about Rituximab and why it may work in only about 30% of the ME/CFS population.
I just wanted to share the studies and findings discussed in this interview because it seemed to cover some possible answers as to why this drug may only work in a subset of ME/CFS patients, Note that this interview appears to have been published on Youtube in 2015. Dr. Mikovits states that she was in contact with the Norwegian doctors (Fluge and Mella) back in 2010 while they were investigating how this drug might or might not work in ME/CFS patients.
I think the interview was worth my time to watch in its entirety to get a better understanding about the science behind the use (or trial) of drugs like rituximab, ampligen or even anti-retrovirals in illnesses such as ME/CFS. I believe that others might also find what is being discussed in this interview to be very interesting.
Since it appears that this video has had under 500 views, it may not have been seen or even watched in its entirety by many in the ME/CFS community. At minute marker 3:24 - 7:26, there is a discussion about Rituximab and why it may work in only about 30% of the ME/CFS population.
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Snow Leopard
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No. Such tests are not useful for ME or CFS or autoimmune diseases.
If you had the primary humoral immunodeficiencies (lack of B-cells) mentioned in that quote, you would have become very ill with infections as a child and you would certainly have known about it.
https://en.wikipedia.org/wiki/Primary_immunodeficiency
Thank you @Snow Leopard for letting me know that you do not believe these other CD20 tests would be useful for ME or autoimmune illnesses.
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I do an overnight 13 hour fast for weight management; I don't have ME/CFS but I have a family member whose ill.What about trying an overnight 13/14 hour overnight fast i.e.on a daily basis?
I rather think that a 24-36 hour fast twice a week, with a 16 hour daily fast, is likely much more effective Recent research suggests doing that sort of 24 hour fasting twice a week is optimal. For me, the tricky part is coming off the fast. I want to prep my gut with preferred probiotics. L. rhamnosus, Saccharomyces Boulardii, and a generic Lactobacillus probiotic is what works for me. But it takes discipline to stick to this kind of health regime, often more discipline than I might have.
Paul
I rather think that a 24-36 hour fast twice a week, with a 16 hour daily fast, is likely much more effective Recent research suggests doing that sort of 24 hour fasting twice a week is optimal. For me, the tricky part is coming off the fast. I want to prep my gut with preferred probiotics. L. rhamnosus, Saccharomyces Boulardii, and a generic Lactobacillus probiotic is what works for me. But it takes discipline to stick to this kind of health regime, often more discipline than I might have.
Paul
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CycloME results were supposed to be released, and published, towards the end of 2017. Then they said the first half of 2018. It is now the middle of July.
Does anyone know what is going on?
Does anyone know what is going on?
deleder2k
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It is discussed here: https://forums.phoenixrising.me/ind...ss-treating-me-patients-with-rituximab.35955/
To be brief: Much of what is said here is wrong. We also know much more today about RTX for ME.
I saw your comments about a CD19/CD20 test. There is no point in doing it prior to RTX. You could do it after the two first infusions to confirm that the B-cell level is at zero or around zero, but I think there's no point in that outside of a study.
The rituximab study will be published soon. We know that the group who did get rituximab didn't get better than those who got placebo. I am sure that we will learn from the study, and they've probably found several interesting things in their substudies, but RTX for ME is dead at this very time. Reading the study and getting the details will be interesting, but since it was not statistically significantly better than placebo, it means probably a handful at most could have experienced an effect with RTX without RTX being significantly superior to placebo.
I am sure they will continue the lab work at Haukeland, but I don't know how much time they will spend on this. A researcher from UBC, Canada was trying to make a biomarker so that he could predict those who would benefit from RTX. He stopped the study when he heard that the trial was negative. That says a lot. Prof Jonathan Edwards said it was a waste of time and resources to pursue RTX like it was planned.
With that said we have a lot of good stuff going on. A lot. I don't know when the cyclo study is to be published, but I know that the RTX study manuscript was sent to the paper a few months ago. Lets hope it is published soon!
@Woodyrob, that is what I call harassment. Your conspiracy theory is full of errors.
Gingergrrl
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I am confident there is a group of us with many different forms of autoimmunity including "autoimmune dysautonomia" (which may have a more official term in the future!) who can be greatly improved by high dose IVIG and Rituximab. I think some in that group will also have ME/CFS vs. some will have been completely misdiagnosed with it (but believe that they have it). If that group can be discovered through accurate testing, I believe Ritux can help them. I also believe there is a group that it would not help (neutral) and a group that it would make worse. I think further study is critical and hoping it is not all discarded never to be looked at again.
As far as the results of Rituximab we are still waiting for the paper. They have confirmed a negative study, but we still need the paper to be published before we know what they have learned in the study other than that Ritux only worked for a percentage of the participants. As far as ongoing studies at Haukeland; They are testing another drug on ME patients (Cyclofosfamid). That is a 2 part study. Part 1 was finished in August 2017. From the results of part 1 they have decided to continue to part 2. Also the results in part one is to be published in 2018. They said early half of 2018, but still to come.
Quote from Haukeland:
Based on precautionary analyzes, we see that there is a basis for continuing cyclophosphamide trial for patients with ME / CFS, and has prioritized the work on new protocols and ethical approval for Part B of the study.
(google translate)
They are also continuing the work on the bio bank and still searching for mechanics
Another quoute from Haukeland:
In addition, the group conducts continuous laboratory trials based on one biobank with blood samples and other sample material from participants in clinical trials. The research aims at mapping disease mechanisms at ME, and identifying biomarkers for the disease.
Studying on cell metabolism at the University of Bergen and immunological factors at Oslo University Hospital, hosted on the basis of this research biobank.
Quote from Haukeland:
Based on precautionary analyzes, we see that there is a basis for continuing cyclophosphamide trial for patients with ME / CFS, and has prioritized the work on new protocols and ethical approval for Part B of the study.
(google translate)
They are also continuing the work on the bio bank and still searching for mechanics
Another quoute from Haukeland:
In addition, the group conducts continuous laboratory trials based on one biobank with blood samples and other sample material from participants in clinical trials. The research aims at mapping disease mechanisms at ME, and identifying biomarkers for the disease.
Studying on cell metabolism at the University of Bergen and immunological factors at Oslo University Hospital, hosted on the basis of this research biobank.
deleder2k
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But how many ME patients diagnosed after the CCC will have "autoimmune dysautonomia"? I have not read much about it, but how does it relate to ME? If say 40% of patients with ME had it and rituximab did help a significant group of patients we would probably have seen a positive result in the Haukeland study.
I don't rule out that some patients with ME may benefit from Rituxmab, but it is pretty clear that we're talking about extremely few patients. My understanding if that one don't find a way to figure out responders before the drug is given, the rtx track is dead at the moment. It is very telling that the UBC researcher which was awarded a grant to predict likely responders of RTX has quit because it was a null trial.
I think it is important that we learn from this, and that the community does not spend to much resources on this. It is nowhere near what we hoped for. With that said, I can't wait for the cyclo study.
Gingergrrl
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I agree and I think the paper will be helpful so we can learn more about the patients who were responders. I suspect that there is a large percentage of people around the world (and I've heard it's as high as 40% in the UK) who are given an ME/CFS diagnosis when in reality, they have been misdiagnosed. I think proper diagnosis will help both the individual patients and will improve the quality of the studies (b/c it will be a more homogenous group in future studies with the same diagnosis).
I actually think the percentage will be fairly solid. It seems that there is a quite a bit of overlap with POTS and autonomic disorders and within that group, there will be a decent subgroup with Autoimmune POTS or an autoimmune cause of their dysautonomia. I think a lot of future research will be going in this direction.
Because there will be individuals who truly have BOTH ME/CFS and Autoimmune POTS/Dysautonomia or another autoimmune disease, or there will be individuals who were given an ME/CFS label but actually never had it and had AI disease instead. Either way, proper diagnosis, studies, and treatments will help these patients and future studies.
I have no idea if it is 40% but even it is 10%, it would be good to understand the sub-groups (in general, not just the Haukeland Study) so treatments can be more individualized and focused.
I have to agree.
So this was not the cure that everybody hoped for... But still, it has become clear that it has worked for a few (we dont know the percentage yet). And in my opinion, that is another clue. The question is ... Why did it work for some and others not? And that answer is yet to come. But I have no doubt that they will probably find the cause of that question at some point in their research.
Nickster
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My son Nick will be trying Ritixun next week for his autoimmune issue (Sjondrome Syndrome). He will have 2 iv doses 2 weeks apart and than every 6 months. Once this is done, they will try to ween him off the steroids (prednisone 20). The UCLA rheumolologists were very encouraging with the success of Ritixun and Sjondromes/vasculitis. They have experienced success with this treatment. So we shall see.
Gingergrrl
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I totally agree and well said!
That is great news re: Nick! I was curious when you said "Sjondrome", do you mean Sjogrens or something else?
Nickster
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Sorry I meant Sjogrens Syndrome. I was typing with my thumbs.