Rituximab Phase III - Negative result

[Martin aka paused||M.E.]

That was a German soccer player. There was an interview with them, and Miktovits. When they talked she said that with the dosage they gave him that it was no wonder that he became more ill. It's in here somewhere. The intro starts out in German, but the rest is in English.

Yep, it was Olaf Bodden from 1860 Munich.
BTW; Mr. Edwards already explained that her statement about the dosage is total nonsense I think she should stay away from giving medical advices...

 

[Nico]

Yep, it was Olaf Bodden from 1860 Munich.
BTW; Mr. Edwards already explained that her statement about the dosage is total nonsense I think she should stay away from giving medical advices...

Ok, I didn't know that. I just remembered this interview.

 

[Gingergrrl]

@lnester7 my puppy died too ! :-(

I missed this the first time I read the thread and @Dechi, I had no idea that your puppy died and am so sorry. Did this just happen?

Technical speaking that could be due to placebo effect too...

I guess in my case, I don't understand how things could be placebo? I can stand and wash dishes for 30 min and take a shower with zero assistance and have many other examples (and could not do these things for 3+ yrs). But if it is placebo, I will take it and accept it!

 

[Martin aka paused||M.E.]

I guess in my case, I don't understand how things could be placebo? I can stand and wash dishes for 30 min and take a shower with zero assistance and have many other examples (and could not do these things for 3+ yrs). But if it is placebo, I will take it and accept it!

Don’t get me wrong. I didn’t say that your response is placebo! I meant that there are no objective measurements to rule out placebo except from statistics ... but I could be wrong?!?

 

[Gingergrrl]

Don’t get me wrong. I didn’t say that your response is placebo! I meant that there are no objective measurements to rule out placebo except from statistics ... but I could be wrong?!?

Hi Martin, sorry I didn't mean at all that you were saying that my response was placebo! I was just trying to wrap my mind around how objective measurements (for anyone) could be placebo? I understand how questionnaires can be placebo (whether about fatigue, depression, etc) but not how blood tests, CPET tests, spirometry, 6 minute walk test, etc could be placebo?

 

[Murph]

Boy this is some horrible news to wake up to.

The. Worst. Having something to hope for is just so positive and helpful. This study felt like a shortcut to a cure. Now we're back in the biomedical research maze, full of underpowered studies making ambiguous contributions to the primary research.

I suppose we wait to see if some of the substudies or non-primary endpoints show us something.

EDIT: Maybe cyclo is our new target for hope.

 

[suzhannah]

Omg am so dreadfully disappointed.. Wanted my life back after 7 years practically bedbound and definitely housebound and pain for over 20 years this is terrible news

 

[dannybex]

I'm not sure if this question has been asked and answered, but I thought there was a gag order or some such restriction against talking about the study until it is published next spring.

???

 

[bertiedog]

I believe it is autoimmune for a sub-group and that it is not one disease. But I of course could be 100% wrong and have nothing solid to back up my opinion.

I am so pleased that you have had some excellent gains so far.

Did you have any other type of autoimmune condition that you knew of before treatment?

Glad to get some good news today!

Pam

 

[Murph]

One of the ways the study can fail is that the Rituximab helps a decent share of people but the placebo group also produces big gains.

Which is a far more ambiguous way to fail your primary endpoint than if it doesn't help many people. I wonder if this happened?

 

[JES]

There could also be some spontaneous remissions among responders in phase 2 study, which would affect the result when the sample size was so small.

 

[Gingergrrl]

Did you have any other type of autoimmune condition that you knew of before treatment?

I found out that I had Hashimoto's Disease in 2013 (which is autoimmune thyroid disease) but I still feel this is a minor part of my illness. Many docs told me that Hashi's was the gateway to other autoimmune diseases so I guess I should not be surprised.

It was not until 2016 that we discovered I had all of these auto-antibodies (GAD65, N type calcium channel Ab, 7 of the 9 Cell Trend Abs, etc) but in my case they do not form a cohesive disease vs. contribute to a weird cluster of symptoms. My doctors believe some day my disease will have a name and when you fall into the nameless category, most docs label you with "CFS" but without a biomarker, no one really knows what this means.

So to answer your question to the best of my ability, I had "Autoimmune POTS" and "Mast Cell Activation Syndrome" going into treatment plus a bunch of other autoantibodies which correlated with autoimmune illnesses in which I met some of the criteria, but not enough to have the diagnoses. No one wants the answer more than me and if I knew, I believe it could help others.

 

[jaybee00]

For what it’s worth, I did hear of a patient in the placebo arm who was a responder.

 

[Aubry]

Minute 01.23 What do you expect from Rituximab?

 

[FMMM1]

I can't say how sad I am at this initial news, but unfortunately that's good science. My heart is breaking for the wider impact of this but this is what good science does and Fluge and Mella have been extraordinary scientists and I am so grateful for what they have done and continue to do. Would like to see P values etc but , damn damn damn.

EDIT: On a positive note perhaps F and M have elucidated some findings that are important through this research such as PDH, PDK1 etc.....it may still come to fruition.
B

Couldn't agree more sad that this didn't work and grateful. As you say they may have discovered something very useful re PDH, PDK.

 

[pibee]

Minute 01.23 What do you expect from Rituximab?

he is actually expecting Phase III to be successful, based on what he said here Nobody expected it to solve ME for good, so not sure I get you point..in no way was he disagreeing with the hypothesis of the trial... even said it's good diagnostic measure to confim B cells involvement

 

[bertiedog]

I found out that I had Hashimoto's Disease in 2013 (which is autoimmune thyroid disease) but I still feel this is a minor part of my illness. Many docs told me that Hashi's was the gateway to other autoimmune diseases so I guess I should not be surprised.

I was also diagnosed with Hashimotos in 2003 and still have slightly raised antibodies despite treatment. I also have adrenal insufficiency but have never been tested to see if antibodies are involved. I am working at improving my gut at the moment to see if that helps (don't want to derail the thread so will leave it at that).

Good luck with your further treatments and great that you keep us informed of how you react to them.

Pam

 

[Hope123]

I found out that I had Hashimoto's Disease in 2013 (which is autoimmune thyroid disease) but I still feel this is a minor part of my illness. Many docs told me that Hashi's was the gateway to other autoimmune diseases so I guess I should not be surprised.

It was not until 2016 that we discovered I had all of these auto-antibodies (GAD65, N type calcium channel Ab, 7 of the 9 Cell Trend Abs, etc) but in my case they do not form a cohesive disease vs. contribute to a weird cluster of symptoms. My doctors believe some day my disease will have a name and when you fall into the nameless category, most docs label you with "CFS" but without a biomarker, no one really knows what this means.

So to answer your question to the best of my ability, I had "Autoimmune POTS" and "Mast Cell Activation Syndrome" going into treatment plus a bunch of other autoantibodies which correlated with autoimmune illnesses in which I met some of the criteria, but not enough to have the diagnoses. No one wants the answer more than me and if I knew, I believe it could help others.

Now that is interesting. Thanks for sharing your history. You might have posted this before and since I'm mostly off-forum, I likely missed it: did you ever have other signs of inflammation, e.g. elevated ESR, CRP, cytokines?

The news is sad but I do hope that they will follow up on looking at subgroups. In a way, I am not entirely surprised that positive results would be hard to find.

1) The more I examine the ME-ICC and CCC, the more issues I see with them. The number and diversity of symptoms in those criteria are such that the combinations of symptoms patients have greatly exceed those of even Fukuda, which already generates 163 different symptoms combinations. Additionally, a close read of the criteria shows that a patient need not have cognitive issues in either ME-ICC or CCC to qualify and they do not need to have sleep issues to qualify for ME-ICC. This is because both criteria allow for options, e.g. need to have at least one symptom from 3 out of 4 categories. I do not know the symptom makeup of the Fluge/ Mella's group is though -- hope they say something about this in their paper.

2) The work they collaborated on with the Scheibenborgen's group in Germany is interesting. In one paper, they showed about 25% of patients had reduced IgG and 25% of patients had elevated IgG. The elevated IgG group were more likely to have autoantibodies. The former group were prone to infections. In my very simplistic way of thinking, if you have high IgG, reducing your B-cells and consequently antibodies might not be helpful and instead some of this group might benefit from IVIG instead. Whereas the higher IgG group might signal those with autoantibodies and potentially an autoimmune disease or mechanism. However, a twist here is not everyone with elevated autoantibodies responded to Rituximab even; however, those who did showed a reduction in autoantibodies later.

 

[Nickster]

@Marky90 or @deleder2k Is there a link to the study results and I am missing it? Or was it just a press announcement and the results are to follow later?

I have no idea if this is helpful to anyone, but I have responded to Rituximab and I am certain that there are others in the world who must be in the same "sub-group" as me. I know I cannot have a disease that no one else on the planet has and am not that unique.

My doctor feels that I have "Autoimmune POTS" (and he believes that some day this term will be understood by medicine even though it is not at present). He also feels I have something similar to LEMS b/c of the calcium autoantibody that weakened my muscle strength and breathing, in addition to have POTS. Doctors have told me that people with just POTS do not have the level of muscle and breathing issues that I had.

I am absolutely not even close to being cured or near pre-illness levels but my MCAS/allergic reactions remain in remission, my muscle strength is now normal, my breathing is better, POTS better, walking better, etc. I wish I knew why the IVIG and Ritux helped me but am certain it can help others with similar auto-antibody or symptom profiles.

I have no idea what happens when I stop IVIG and Rituximab, and I may be back at square one. The best I hope for is remission, and I do not believe there is a cure.

@Gingergrrl Do you think you had more benefit from IVIG vs Rituximab? Or what about MCAS treatments vs Rituximab? Just curious.
Thanks,

 

[pibee]

2) The work they collaborated on with the Scheibenborgen's group in Germany is interesting. In one paper, they showed about 25% of patients had reduced IgG and 25% of patients had elevated IgG. The elevated IgG group were moce likely to have autoantibodies. The former group were prone to infections. In my very simplistic way of thinking, if you have high IgG, reducing your B-cells and consequently antibodies might not be helpful and instead some of this group might benefit from IVIG instead. Whereas the higher IgG group might signal those with autoantibodies and potentially an autoimmune disease or mechanism. However, a twist here is not everyone with elevated autoantibodies responded to Rituximab even; howevec, those who did showed a reduction in autoantibodies later.

this confuses me, are you actually saying, you'd expect rituximab not to work for those with autoimmunity -high IgG and autoantibodies