Rituximab Phase III - Negative result

[Gingergrrl]

@Gingergrrl, from everything I've read, you have every chance of success at this point. You had a plethora of awful antibodies and a history of EBV and mold. Getting rid of the triggering conditions (as much as one can get rid of EBV), and attacking the antibodues, first with IVIG and then with Rituximab should clean them out of your system. As long as you steer clear of future triggers, you should have every chance of success. Which is wonderful!

Thanks @Learner1 and I so hope and pray that you are right! I know that IVIG & Rituximab have knocked down and eliminated the autoantibodies to the lowest levels possible and my improvements have exceeded my expectations. I am trying to be in the moment and not worry about what happens when the treatments stop but (our) doctor calls this the "ten million dollar question" and just doesn't know if the new B cells grow back healthy or if they grow back damaged and pathogenic with the same autoantibodies and symptoms.

I am starting to do a lot more (except I am temporarily on house arrest taking care of my dog since her back surgery LOL). I am afraid this will all go away when the treatments stop and I wish there were researchers who were really interested in IVIG and Ritux and those who are responders to it (b/c we are worldwide and all across the internet)! We must share some commonality but I don't know what it is.

Unfortunately, we are a mixed bag of patients, sharing symptoms but having a diverse group of genetic and environmental factors, so there's no one identical to you. So, we can each just to the best we can to get through our individual situations.

I agree that each one of us is different, both genetically and environmentally, but I hope the research will some day discover enough similarities to figure out what is going on... or I can dream of that day LOL.

Thank you for your reply. That treatment doesn't sound like a whole lot of fun. I'm glad you're feeling better. I think they (researchers) should study those who respond to immunosuppressants e.g. to see if they can identify autoimmune antibodies. Mark Davis (OMF), and Dr Unutmaz (NIH Research Centre), among others, are looking at the immune system; hopefully we will see some significant progress in the near future.

I am happy to reply and I hope my second response made more sense than my first! I know there are definitely people researching the immune system from all angles, and I am very grateful for them, and am especially excited about the new autoantibody research in POTS.

Immunosuppressants are a great way to end up with cancer or sepsis. Figuring out how to reverse autoimmunity vs. suppressing the immune system seems wiser.

I might be wrong but I have viewed IVIG as an immune-modulator (vs. suppressant) and viewed Rituximab as a very targeted chemo or monoclonal antibody that only targets the B cells and nothing else. I have avoided hardcore immunosuppressants like Cell Cept and Imuran (even though one Neuro recommended them) b/c of the cancer risk and they scared me overall!

 

[Learner1]

I might be wrong but I have viewed IVIG as an immune-modulator (vs. suppressant) and viewed Rituximab as a very targeted chemo or monoclonal antibody that only targets the B cells and nothing else. I have avoided hardcore immunosuppressants like Cell Cept and Imuran (even though one Neuro recommended them) b/c of the cancer risk and they scared me overall!

Our doctor calls IVIG a replacement therapy. It boosts the immune system, and is not an immunosuppressant.

I was referring to Humira, Enbrel, Remicaid, etc. which are immunosuppressants used in autoimmune diseases. I've met several people with cancers caused by them and a couple of deaths from sepsis that went unnoticed due to the immune system being suppressed until it was too late.

It is important to look at all the options and choose as wisely as possible given one's personal situation and not choose treatment just because it worked for someone else.

 

[tiredowl]

So, I was able to contact a private hospital here.They say they would be fine with me coming in for a consultation whether I could be a candidate for ritux.
I'm wondering if I should give it a shot or just not bother wasting my energy on it?
I beleive my CFS to be largely autoimmune, autoimmune diseases run in my family. MS, Arhritis, diabetes etc.
So wiping out the b cells could possibly be a cure. But I'm scared of the side effects, or what if my CFS is caused by an underlying infection they haven't discovered. I've wondered if fungal infections could be something since I was helped by ketokonazole once.
I'm completely bedridden most days. Can sometimes go for light walks but it's so uncomfortable because I feel chills all the time, especially upon moving myself.
Been sick for many years, I'm seeing this as some kind of last resort, mostly because it's quite serious to use immunosuppressants like this and potential side effects that can happen.

 

[Gingergrrl]

I was referring to Humira, Enbrel, Remicaid, etc. which are immunosuppressants used in autoimmune diseases. I've met several people with cancers caused by them and a couple of deaths from sepsis that went unnoticed due to the immune system being suppressed until it was too late.

I have never taken any of those meds and am not too familiar with them (besides the endless ads on TV)! I know when they list the side effects (on TV) they always mention cancer and PML but I'd never heard them mention sepsis. That is scary!

It is important to look at all the options and choose as wisely as possible given one's personal situation and not choose treatment just because it worked for someone else.

I agree and we chose my course of treatment based on my own personal situation and it had nothing to do with what anyone else was doing. From 2013 to 2016, I tried things that had helped others without any real understanding of my situation and most were neutral or made me worse. I am willing to take huge risks, if I have done my research and think the potential outcome is worth it.

 

[M Paine]

Has there been any news or extra information from Fluge & Mella since this thread was started in November 2017

There are 17 pages of posts, and I have not kept up-to-date with this. All I know is that the Phase III trial was unsuccessful.

Thanks in advance

 

[FMMM1]

Has there been any news or extra information from Fluge & Mella since this thread was started in November 2017

There are 17 pages of posts, and I have not kept up-to-date with this. All I know is that the Phase III trial was unsuccessful.

Thanks in advance

Interesting to see what Fluge & Mella make of this. However, I haven't seen anything and it may take more time.

 

[Murph]

Has there been any news or extra information from Fluge & Mella since this thread was started in November 2017

There are 17 pages of posts, and I have not kept up-to-date with this. All I know is that the Phase III trial was unsuccessful.

Thanks in advance

Nope. 17 pages without a peep from Norway. If they'd released anything I'm sure we'd have got to 170.

 

[Cam Newton]

CycloME results should be published very soon. They are still targeting to publish in the first half of 2018.

 

[crypt0cu1t]

So, I was able to contact a private hospital here.They say they would be fine with me coming in for a consultation whether I could be a candidate for ritux.
I'm wondering if I should give it a shot or just not bother wasting my energy on it?
I beleive my CFS to be largely autoimmune, autoimmune diseases run in my family. MS, Arhritis, diabetes etc.
So wiping out the b cells could possibly be a cure. But I'm scared of the side effects, or what if my CFS is caused by an underlying infection they haven't discovered. I've wondered if fungal infections could be something since I was helped by ketokonazole once.
I'm completely bedridden most days. Can sometimes go for light walks but it's so uncomfortable because I feel chills all the time, especially upon moving myself.
Been sick for many years, I'm seeing this as some kind of last resort, mostly because it's quite serious to use immunosuppressants like this and potential side effects that can happen.

Please let me know if you go through with it, I'm very interested to hear your results!

 

[Woodyrob]

It's a dangerous drug even for those who are sure it's going to work like cancer. However for ME/CFS there have been other trials besides the Norwegians, like in Germany that had to halt a trial because 10 out of 10 didn't improve and 2 got worse.
In the Norwegian trials participants had said they saw other patients worsening in the trials.
Personally I'm now quite sceptical of those Norwegian researchers to the point I think they may have twisted the data as they we getting exceptionally high results at around 67% of patients improving during phase 1 and 2 trials yet the phase 3 trial showed no beneficial result whatsoever. That to me suggests they did it all for the funding, I maybe wrong, but there'd be no way I'd risk my health worsening with Rituxmab unless there's a clear autoimmune subset that
have problems with their CD20 White B blood cells which Rituximab binds to.

The interesting thing is why wasn't there even some smaller effect in the phase 3 trial?, because surely the autoimmune subset were in it, so you'd expect to see a certain percentage above placebo get better. It would still be noticeable. Yet we haven't heard about them or if any people who improved even exist.

So my advice is don't take it, as is a very dangerous drug (it killed a patient of my doctor in an unrelated disease)
Plus it's incredibly expensive.

Try LDN in the meantime

 

[FMMM1]

So, I was able to contact a private hospital here.They say they would be fine with me coming in for a consultation whether I could be a candidate for ritux.
I'm wondering if I should give it a shot or just not bother wasting my energy on it?
I beleive my CFS to be largely autoimmune, autoimmune diseases run in my family. MS, Arhritis, diabetes etc.
So wiping out the b cells could possibly be a cure. But I'm scared of the side effects, or what if my CFS is caused by an underlying infection they haven't discovered. I've wondered if fungal infections could be something since I was helped by ketokonazole once.
I'm completely bedridden most days. Can sometimes go for light walks but it's so uncomfortable because I feel chills all the time, especially upon moving myself.
Been sick for many years, I'm seeing this as some kind of last resort, mostly because it's quite serious to use immunosuppressants like this and potential side effects that can happen.

Barely read your post above.

Check out Mark Davis's talk at OMF Community Symposium in September 2017. Mark presented results showing clonal expansion (activation) of T-cells. He talks bout ME/CFS being an autoimmune T-cell disease. Basically if your T-cells are responding to a self antigen then it's a T-cell autoimmune disease.

I'm interested in B-cell autoimmunity in ME/CFS and I think that work should be persued (*Scheibenbogen/Light's etc.). However, I'm not clear that anyone has good data showing autoantibodies produced by B-cells i.e. B-cell autoimmunity. If B-cell autoimmunity were a common cause of ME/CFS then presumably rituximab would have worked; the trial was negative. However, a sub-group could still be B-cell autoimmunity*.
What/have autoantibodies been found in your case and if so what ones/how good are the tests? Look at OMF's News Experts Blog [https://www.omf.ngo/2018/02/12/tweak-assay-bolster-disease-detection-stanford-medicine-news-center/]. The current tests for adrenergic receptor antibodies etc. should I assume be revised to see if they can improve the accurcy - reduce false negatives/positives.

Check out Unutmaz's work; he's due to do a webinar (on 19th July?). He seems to be looking at leaky gut and seems to have found exhausted T-cells in the gut (too much exposure to bacteria from the gut). Hence he got an NIH grant.

Ron Davis's group (Phair) is working on metabolic trap; results out end of summer - could be the whole thing is consequence of metabolic trap and reversible. Check out Chris Armstrong's 2016 Webinar; he appears to have proposed the whole metabolic thing some time ago.

Sorry for the rushed response and good luck; many of us are pretty desperate to see a cure/substantial progress in this.


*DN: from the web- Immunoadsorption to remove ß2 adrenergic receptor antibodies in ...
https://www.ncbi.nlm.nih.gov/pubmed/29543914
by C Scheibenbogen - ‎2018 - ‎Cited by 1
15 Mar 2018 - ... adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME. ... (2)Berlin-Brandenburg Center for Regenerative Therapies (BCRT)


.

 

[Sushi]

The interesting thing is why wasn't there even some smaller effect in the phase 3 trial?, because surely the autoimmune subset were in it, so you'd expect to see a certain percentage above placebo get better. It would still be noticeable. Yet we haven't heard about them or if any people who improved even exist.

I believe there were patients who improved. We have not had the full report yet and the "failure" seems to have been as a drug that would help a significant percent of patients.

 

[pcmenten]

So, my understanding of Rituximab is that it is intended to lower white blood cell count. Because EBV infects these cells, there has been hope that it would relieve ME/CFS symptoms.

It's also my understanding that fasting will lower white blood cell counts. I have tried fasting and I've felt better after 36 hours of a water-only fast. In fact, I've just talked myself into doing it again.

Anybody else?

Paul

 

[JES]

So, my understanding of Rituximab is that it is intended to lower white blood cell count. Because EBV infects these cells, there has been hope that it would relieve ME/CFS symptoms.

It's also my understanding that fasting will lower white blood cell counts. I have tried fasting and I've felt better after 36 hours of a water-only fast. In fact, I've just talked myself into doing it again.

Anybody else?

Paul

Rituximab acts on specific white blood cells called B cells. And it not only lowers them, it basically depletes them so that you will have a very low level of remaining circulating B cells after multiple treatments with Rituximab. So I don't think it's very comparable to fasting.

Fasting is interesting though, it was in the news a couple of years ago that fasting could regenerate the immune system in some ways (source). From my understanding, fasting as you say causes a drop in the WBC count after certain amount of hours, but when you stop the fast the immune system will rebound and prompt the stem cells to produce new white blood cells. This effect is very interesting, but unfortunately to get this benefit you would have to fast continuously for around 72 hours. I never managed much more than a day before feeling too weak to walk etc.

 

[Wally]

I have a question* about the Norwegian study and for anyone who has tried Rituximab outside of this study.

Before treatment were you or the study participants tested for a CD20 marker? (See, this article for discussion re CD20 marker and lymphoma - https://www.verywellhealth.com/cd20-cd-marker-2252140 . I have always been a little unclear what CD20 refers to as it appears that it is a gene (see, https://www.ncbi.nlm.nih.gov/pubmed/11225995) and it is an antibody to CD20 that knocks out the B-Cells or T-Cells that it has attached to and are associated with lymphoma, RA or MS (the B-cells and T-cells in these illnesses have also been found to be reservoirs of EBV). Am I way off base in my understanding of what CD20 is, and its involvement with B or T cells and Rituximab?

*(I apologize if this question has been asked and answered in this thread or elsewhere just not feeling well enough to do a deep dive to search. But I was interested in pursuing it following the outcome of the Norwegian trials. Someone with a lot of knowledge about this drug (back in the early days when it was seen as improving ME/CFS in a small group of cancer patients) told me to not even think about trying it without finding out if I had a C20 marker. I think they said a CD20 antibody marker, but I never really understood if I heard exactly what marker they were suggesting be tested.)

I was wondering if there is a CD20 test that is routinely done for people who are going to try this drug whether or not they are being treated for cancer, RA or an illness other than ME/CFS. (I never pursued taking the drug myself, so I never found out what pre-testing would need to be done, I was just told I would be a candidate for the drug based on my medical history of high EBV titers.). Also, I was wondering if any correlation between the C20 marker and ME/CFS patients has ever been found?

I was also wondering if the thread started by @Ecoclimber in 2017 might provide some more insight into why the Norwegian Reituximab trial may have turned out the way it did? See, https://forums.phoenixrising.me/index.php?threads/cd20-antibodies-deplete-ebv.52838/

 

[Cam Newton]

In the Norwegian trials participants had said they saw other patients worsening in the trials.
Personally I'm now quite sceptical of those Norwegian researchers to the point I think they may have twisted the data as they we getting exceptionally high results at around 67% of patients improving during phase 1 and 2 trials yet the phase 3 trial showed no beneficial result whatsoever. see a certain percentage above placebo get better. It would still be noticeable

This stuff happens all the time. Early phase trials often don’t pan out. Also, just because there was no statistically significant improvement over placebo, doesn’t mean no one got better.

Your post is idiotic and detrimental to the research community.

 

[Snow Leopard]

Before treatment were you or the study participants tested for a CD20 marker?

This is explained in the link you posted, but nevertheless:

CD20 is a cell membrane protein expressed on all almost all mature B-Cells. This is why Rituximab, which is a manufactured antibody causes the immune system to attack B-cells specifically.

In the case of lymphoma, it depends on the specific cell type. If the lymphoma originates from mature B-cells, then the cancerous cells will express CD20 and Rituximab will target these cells. So the CD20 profiling test is for lymphoma patients, not for patients with autoimmune disorders.

 

[tiredowl]

Please let me know if you go through with it, I'm very interested to hear your results!

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.

 

[FMMM1]

It's a dangerous drug even for those who are sure it's going to work like cancer. However for ME/CFS there have been other trials besides the Norwegians, like in Germany that had to halt a trial because 10 out of 10 didn't improve and 2 got worse.
In the Norwegian trials participants had said they saw other patients worsening in the trials.
Personally I'm now quite sceptical of those Norwegian researchers to the point I think they may have twisted the data as they we getting exceptionally high results at around 67% of patients improving during phase 1 and 2 trials yet the phase 3 trial showed no beneficial result whatsoever. That to me suggests they did it all for the funding, I maybe wrong, but there'd be no way I'd risk my health worsening with Rituxmab unless there's a clear autoimmune subset that
have problems with their CD20 White B blood cells which Rituximab binds to.

The interesting thing is why wasn't there even some smaller effect in the phase 3 trial?, because surely the autoimmune subset were in it, so you'd expect to see a certain percentage above placebo get better. It would still be noticeable. Yet we haven't heard about them or if any people who improved even exist.

So my advice is don't take it, as is a very dangerous drug (it killed a patient of my doctor in an unrelated disease)
Plus it's incredibly expensive.

Try LDN in the meantime

Only scanned your email. I agree with some of it e.g. rituximab is dangerous. I'm also surprised that any doctor would offer to treat someone with ME/CFS with rituximab at this time.

Look at a successful (still work to do) B- cell autoantibody disease story i.e. NMDA receptor antibody encephalitis. The disease presents like schizophrenia. Recently UK researchers tested people with schizophrenia for these autoantibodies and treated those who were positive and negative for the antibody*. All those who tested positive recovered and the same portion of those who tested negative also recovered. The reason was of course that the test only finds some of the positives. Ron Davis recently published details of a method to improve these tests [https://www.omf.ngo/2018/02/12/tweak-assay-bolster-disease-detection-stanford-medicine-news-center/].

The problem with the rituximab trial, in my view, may have been the poor quality of autoimmune tests e.g. for adrenergic receptor antibodies. Half way through the trial a study was published on autoantibody tests on the participants [Scheibenbogen - adrenergic receptor antibodies etc?]; Jonathan Edwards flagged up his concerns i.e. there was no difference between the control/test groups.
I have tried to lobby for better testing method (Davis method). Specifically I asked a United Kingdom member of the European Parliament to ask a parliamentary question on support for research for an improved autoimmune test for adrenergic receptor antibodies; it was never asked.

The Davis (OMF) group seemed to have moved on to T-cell autoimmunity [OMF Symposium September 2017] and metabolism (Phair). Fluge and Mella, as well as rituximab, carried out research which found a reduction in PDH enzymatic activity i.e. impaired metabolism, and endothelial function----. Ron Davis's son is seriously ill; I doubt he would be working with Fluge and Mella unless they were contributing significantly.

I have concerns about how science is funded and there are patents being submitted in relation to discoveries. However, my main concern is that those like Fluge and Mella have access to good quality tests on which to make decisions (e.g. autoantibody tests). Sometimes I've been viewed as challenging doctors; I've tried in vain to explain that I think doctors need proper diagnostic tests etc. Failure to provide proper support to doctors means that it's more likely that the wrong decisions (for patients/doctors) will be made.

I think Fluge and Mella are excellent doctors/medical scientists. We're fortunate to get access to them, and other scientists, but they need support systems (proper tests). We should try to lobby for that i.e. proper tests, rather than complain about the consequences.

Sorry for the (usual) long post!

*[http://www.bbc.co.uk/programmes/art...onditions-be-caused-by-an-immune-malfunction]

 

[FMMM1]

So, my understanding of Rituximab is that it is intended to lower white blood cell count. Because EBV infects these cells, there has been hope that it would relieve ME/CFS symptoms.

It's also my understanding that fasting will lower white blood cell counts. I have tried fasting and I've felt better after 36 hours of a water-only fast. In fact, I've just talked myself into doing it again.

Anybody else?

Paul

Just recalled that I've read that fasting improves your gut flora (microbiome). Maureen Hanson has published a study which indicates increased translocation of bacteria/bacterial proteins in ME/CFS - leaky gut. There have been a number of studies (from Chris Armstrong/Hanson etc?) showing a shift to more pathogenic microbiome in ME/CFS. Chris has suggested that this could be the basis of the chronic sepsis proposed in ME/CFS (https://forums.phoenixrising.me/index.php)?threads/exercise-induced-relapse-autoimmune-theory.52708/) and the post exertional malaise.
In 2017 Hanson participated in a study led by Norweigan researchers (them again) to see if faecal transplants would reset microbiome/reduce fatigue in ME/CFS. Haven't seen results of the faecal transplant trial.
So maybe your fasting improves your gut microbiome/fatigue.

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?

Basically B-cell autoimmunity has slipped back as a research area as rituximab didn't work. Check out the OMF Community Symposium Setember 2017; Mark Davis is proposing T-cell autoimmunity.

Check out Ron Davis's presentation at the symposium and on the OMF site; they are continuing to look for virus's but so far nothing has turned up. However virus's never seem to go away entirely [http://simmaronresearch.com/2018/04/autoimmune-virus-groundbreaking-ebv-finding-help-explain-mecfs/]. Also they are regulators of the microbiome so could potentially be wiping out the good bugs and and thereby allowing the bad ones to increase.

Leaky gut and chronic sepsis/immune activation (Unutmaz/Mark Davis - recent NIH Grant awards), metabolic traps (Pair), HLA & KIR genes i.e.immune/autoimmune genetic research (Ron Davis's - recent NIH Grant award) seem to be hot topics.The breadth of the research is presumably positive.

I've only studied basic chemistry; this stuff is a challenge. Not much settled but Unutmaz (Webinar 19th July?)/Mark Davis/Ron Davis/Chris Armstrong (and others) have been providing hard scientific evidence. Cort Johnson does good reviews of topics.

Suggestion - thinking of lobbying the folks with the money for scientific research (NIH/EU Horizon 2020) possibly via OMF.

Regards