Rituximab Phase III - Negative result

[FMMM1]

Thanks for your reply; I had a look at article. Here's hoping they come up with something.

The United Kingdoms leaving the European Union so a possible source of science funding may not be available (EU Horizon 2020); it will be interesting to see whether the EU starts/increases funding ME/CFS research.

 

[FMMM1]

So much to get through and so little time.
I had 2 full remissions in laat 6 year both after extended h-pylori treatment that probably wiped out my microbiome.....or some other hidden bacteria...who knows.

For around 4 weeks both times was bliss. After that i guess body finds its own natural biome again as natural gut flora repopulates. Then cfs begins all over again.
No amount of probiotics seem to sway it. Maybe its is lower GI.
Bizarrely i never had any GI issues during my cfs.

Couldn't agree more but keep an eye out for Maureen Hanson's collaborative study (with a Norwegian group) on probiotics it's due to end this year i.e. 2017 (check out Hanson's talk at the symposium for details) .

I think the science is complicated and presumably the more important question is how do we get it funded (and fast)?

 

[FMMM1]

It would be nice if you could start a thread with this presentation, this theory deserves much attention, thank you for sharing!

edit: I tryed to move the discussion into this thread about last scientific paper from Neil Mac Gregor, for those who might interested...

Thank you for this I hadn't realised there was a 2016 paper dealing with "changes in kidney's handling of electrolytes". This is also in one of the slides (12 minutes in) it's also covered in the transcript "In patients with pain, there’s a change in kidney function. When the pain is worse, they have lost a lot of amino acids and electrolytes through the urine.".

He also issues a health warning "This is preliminary data. Clearly, this data may still be nothing. But we have to make sure that this makes sense, and that it’s not “no-sense”.

 

[jaybee00]

Some good news though...
A slide showed they found p-001 decreases in flow mediated dilation in both RITUXME-baseline patients and pilot patients, and also a prolonged systemic hyperemia response after a POHR-test (http://www.perimed-instruments.com/post-occlusive-reactive-hyperemia)

They ask why? This is normally seen in patients with severe hypertension. Is the NO-production compromised? And by what? Autoantibodies? (which still is possible, there are other autoantibody-producing cells, and it might be going on in tissue too). Other negative bloodflow-regulators in bloodstream? And how does these findings relate with exercise or brain activity, e.g. reading).

@Marky90

or whomever

Did they suggest anything to treat this decrease in flow mediated dilation? The arginine/citrulline mixture?

 

[Marky90]

@Marky90

or whomever

Did they suggest anything to treat this decrease in flow mediated dilation? The arginine/citrulline mixture?

Cant treat an unknown cause..

 

[msf]

Re "recent KDM paper" could you give the title, I'm interested in having a brief look. Thanks

I have an interest in autoimmune antibodies and can think of one scientist who reckons there's potentially a subgroup of people with ME/CFS where this could be relevant. I'd like to think Prof. Edwards would be around.

http://forums.phoenixrising.me/index.php?threads/dr-de-meirlier-april-and-baff-iga-study.44919/

 

[IThinkImTurningJapanese]

Posts on Neil McGregor's presentation at Open Medicine Foundation's Community Symposium have been moved to this thread,

Neil McGregor’s presentation at Open Medicine Foundation’s Community Symposium

 

[FMMM1]

Some good news though...
A slide showed they found p-001 decreases in flow mediated dilation in both RITUXME-baseline patients and pilot patients, and also a prolonged systemic hyperemia response after a POHR-test (http://www.perimed-instruments.com/post-occlusive-reactive-hyperemia)

They ask why? This is normally seen in patients with severe hypertension. Is the NO-production compromised? And by what? Autoantibodies? (which still is possible, there are other autoantibody-producing cells, and it might be going on in tissue too). Other negative bloodflow-regulators in bloodstream? And how does these findings relate with exercise or brain activity, e.g. reading).

Findings yet to be published..

View attachment 25178

Did a little plagiarism myself; although this is likely from Fluge and Mella themselves: “Fluge and Mella are pursuing autoantibodies in their Rituximab work, and autoantibodies appear to play major role in some cases of postural orthostatic intolerance syndrome (POTS)” [from another webpage - dated October 7, 2017]. So perhaps this subgroup have causal/contributing autoantibodies.

Haven't read your comments or those of others, but just maybe this will help to understand some cases.

Was the "p-001 decreases in flow mediated dilation" a positive response to Rituximab and if so what % of patients responded?

I guess "pilot patients" are participants in previous studies.

Sorry if you've already explained this in previous posts.

 

[Gingergrrl]

Did a little plagiarism myself; although this is likely from Fluge and Mella themselves: “Fluge and Mella are pursuing autoantibodies in their Rituximab work, and autoantibodies appear to play major role in some cases of postural orthostatic intolerance syndrome (POTS)” [from another webpage - dated October 7, 2017]. So perhaps this subgroup have causal/contributing autoantibodies.

@FMMM1 I was curious where your quote came from re: Fluge & Mella from 10/7/17? I am thrilled (from the quote) if they are pursuing autoantibodies in their Rituximab work and the role that they play in some cases in autoimmune POTS b/c this is exactly MY situation! I would love to read more about this. Thank you in advance!

 

[Murph]

@FMMM1 I was curious where your quote came from re: Fluge & Mella from 10/7/17? I am thrilled (from the quote) if they are pursuing autoantibodies in their Rituximab work and the role that they play in some cases in autoimmune POTS b/c this is exactly MY situation! I would love to read more about this. Thank you in advance!

I used a special database exploitattion algorithm I know of and am able to confirm the quote comes from Simarron research, i.e. Cort.

 

[Gingergrrl]

I used a special database exploitattion algorithm I know of and am able to confirm the quote comes from Simarron research, i.e. Cort.

My utter lack of computer skills is unclear if you are joking about the "special database exploitattion algorithm" or if this is a quote from Fluge & Mella that was reported on by Cort? How would I find the original if it is out there?

 

[IThinkImTurningJapanese]

How would I find the original if it is out there?

Special Database Exploitation Algorithm

 

[FMMM1]

I used a special database exploitattion algorithm I know of and am able to confirm the quote comes from Simarron research, i.e. Cort.

Yea but I'm a little worried in case the quote comes from an earlier conversation i.e. before the study was unblinded (September 2017). However, if "p-001 decreases in flow mediated dilation" is a positive response to Rituximab then this quote could provide a possible answer i.e. "autoantibodies appear to play major role in some cases of postural orthostatic intolerance syndrome (POTS)”.

Hopefully, I haven't falsely raised peoples hopes.

 

[Learner1]

Yea but I'm a little worried in case the quote comes from an earlier conversation i.e. before the study was unblinded (September 2017). However, if "p-001 decreases in flow mediated dilation" is a positive response to Rituximab then this quote could provide a possible answer i.e. "autoantibodies appear to play major role in some cases of postural orthostatic intolerance syndrome (POTS).

That is what I was understanding and my hope for Rituximab treatment.

Even with the failure of the trial, it seems that it does help a few patients. Which subset would benefit and why?

Or are there other B cell strategies (like bortezomib) which may be more effective for certain patients? And what are the risks?

The devil is in the details, and it doest seem like there a "one size fits all" solution.

 

[andyguitar]

Somewhere in the dim and distant past there was a reference to CFS being called "T Cell disease" This was years ago. Anyone heard it called that?

 

[jaybee00]

So could use clarification if the difference in flow mediated dilation referred to differences between the control and the treatment group at 24 months in the phase III study or if this is referring to differences between PWCFS in this study versus non-CFS controls...

 

[Gingergrrl]

@FMMM1 What does "decreases in flow mediated dilation" as a study measurement with Rituximab mean vs. the mechanism of Ritux killing the B cells? Thanks!

 

[FMMM1]

@FMMM1 What does "decreases in flow mediated dilation" as a study measurement with Rituximab mean vs. the mechanism of Ritux killing the B cells? Thanks!

Reverting to plagiarism (again)!

I came across this elsewhere on the web "Fluge and Mella believe ME/CFS may be an autoimmune disorder that attacks the blood vessels".

Treatment with Rituximab resulted in better regulation of blood flow in some of those who were treated (%?). I.e. increased blood flow resulted in increased widening of blood vessels (dilation) in these patients.

Treatment with Rituximab wipes out your B-cells. B-cells produce antibodies, including autoimmune antibodies. Therefore, better regulation of blood flow following treatment with Rituximab suggests that some people with ME/CFS may have "an autoimmune disorder that attacks the blood vessels".

I suggest that we are cautious (not necessarily how I am all of the time) and wait to see the paper i.e. have the views of those (Fluge and Mella) who have a better understanding.

 

[FMMM1]

Somewhere in the dim and distant past there was a reference to CFS being called "T Cell disease" This was years ago. Anyone heard it called that?

Google "community symposium on the molecular basis of me/cfs mark davis" and select the YouTube video. It's about 18 minutes long; check out 15.30 minutes [it shows activated T-cells in ME/CFS, Lyme and MS] and 16.40 minutes [summarises findings].

Plagiarism again "The working hypothesis at Stanford University is that ME is an autoimmune disease" [from "Follow ME in Denmark" - check out the article re Mark Davis's presentation].

 

[Learner1]

Today, I'm going to an Immune Deficiency Foundation conference in my city. In digging around in their website, I found this video from their conference earlier this year.

Its a very easy to understand tutorial on the immune system and how autoimmunity can develop in people with immune system defects. Starting at around1:00 he discusses treatment, including high dose IVIG, Rituximab, Bortizimub, and plasmapherisis.

For a subset of patients, it looks like from this angle, Rituximab might work. But likely not everyone here on PR fits this profile. And, as he says, there are risks involved.