De Meirleir is using Rituximab?

[NL93]

I just read this in another topic about De Meirleir. Post from @dadouv47 (Thanks for sharing)

Last thing I wanted to say is about Rituximab because it seemed that you wanted to be treated with that medication. I asked him on the first meeting if he uses that and what he thinks about Rituximab. He said that his opinion changed a bit about that medication, and that he uses a '''prudence'' approach with it. He is using Rituximab for some of his patients ( still don't know if he will recommend it to me) but with really small doses, because he thinks that it could be very dangerous for the body to use higher doses.

This seems quite strange to me? I have never heard of small dose rituximab. I am also curious to know which group of patients he recommends it to.
Does anyone know more about it?

 

[Kati]

I just read this in another topic about De Meirleir. Post from @dadouv47 (Thanks for sharing)



This seems quite strange to me? I have never heard of small dose rituximab. I am also curious to know which group of patients he recommends it to.
Does anyone know more about it?

There is no low doses for this drug. If you want to deplete the B-cell reservoir, you need to deplete it with the dosage that will do the job.
It's not something you just take a little bit of, like Low dose naltrexone. There is no homeopathic doses for this drug and other chemo.

 

[Hip]

@NL93
Very interesting that Dr De Meirleir is now using rituximab. Would you have any web links with more info on this? These really small doses should make rituximab a much more affordable treatment.

And as Dr De Meirleir sometimes publishes papers detailing the results of his treatments, we might get to hear more about his success rate with rituximab, which should add to the rituximab knowledge base.

There is no low doses for this drug. If you want to deplete the B-cell reservoir, you need to deplete it with the dosage that will do the job.

It may actually be feasible to use low doses of rituximab, according to a comment made by @Jonathan Edwards in this post:

Rituximab probably produces complete B cell depletion in most people for three months at a tenth the standard dose and maybe even less.

So low doses may in fact work very well.

 

[Justin30]

@Kati so say if less was given in terms of cc's wouldnt that be considered low dose?

Or even at less cc's would that achieve the same B Cell Depleting agent....

why not use Bellubimab instead cause from what I understand this drug partially depletes B Cells...

OK maybe @Jonathan Edwards can give some feedback as their is another Dr talking about low dose Rituximab as well.....I watched a video where Judy Mikovitz talked with Dr Biegler about this....

I personally think a cocktail of drugs is going to be the ticket to kick this disease.....

The more I think about this and the more I see we are so different...the more I realize we need a center of Excellence using individualuzed therapies like what the Bateman Horne Center was discussing....

 

[Gingergrrl]

One of my doctors also said the ME/CFS protocol is different than the autoimmune protocol and I have now discussed with both a CFS specialist and a rheumy. I do not know anything about dosages or milligrams but I know the number of treatments and possibly the frequency of treatments differs.

 

[Kati]

The chemotherapy (for cancer) treatment usually uses a certain dosage per area of body weight. It's a simple calculation, like 1000 mg/meter square. (Though they usually cap the body surface area at 2)

If after 2 weeks of treatment at a certain dosage all of the B cells are gone, then the treatment goal is achieved. That's what you want achieved.

Edit to add: before deciding what dosage patients should receive, the most pressing question remains 'is this an effective treatment for ME/CFS or a subset of'.

 

[msf]

I have not heard of any of his patients getting Ritux, he may just have been speaking hypothetically.

 

[dadouv47]

Hello there,
I really spoke only 2 minutes with Dr. De Meirleir about rituximab because he's not the kind of doctor that likes to talk a lot ( on the contrary). But yeah, that what he said to me. Maybe it was hypotetically, i can't affirm for sure he's really using it, but that what he said to me. His argument was that high doses of Ritux was like doing a chemotherapy ( he was exaggerating, of course, but he wanted to point out the fact that he considers now that high doses of Ritux are very bad for others parts of the body).
I really can't tell you anything more. That was the brief conversation i had with him about Rituximab.
Regards
David

 

[msf]

Yes, his utterances can be a bit gnomic at times.

 

[msf]

RE: what Kati and Hip have said, perhaps the chemo dose depletes the B-cell population much more quickly than is necessary in RA and possibly ME?

 

[Jonathan Edwards]

Perhaps I should clarify the situation. Kati is basically right. I will try to sort out some of the further confusions. For anyone who is not aware I will just remind people that the autoimmune dose for rituximab was devised by me for very specific reasons to do with mechanisms of autoimmunity.

Firstly, there is no significant difference between standard oncological dose and autoimmune dose. The exact dosages may be calculated differently and the total amount may be divided into four rather than two infusions, but there is no material difference.

Secondly, there is no justification for using a low dose on the basis of 'prudence'. As has been pointed out I have previously noted that the standard dose may be more than a lot of people need to get full depletion for three months. However, to be of much use one needs to deplete for six months and both in routine RA care and in the Haukeland studies doctors have moved towards maintaining B cell depletion for much longer periods, which on balance makes sense, even if there are issues that need keeping an eye on. We also have some quite good evidence for even the standard dose not being as potent as we would really like and not giving full depletion for a small proportion of patients. So justification for reducing the dose would need to be based on a formal dose comparison study.

We have already heard Dr Beiger and Dr Mikovits talking about low doses of rituximab in a way that indicated clearly that neither of them knew what they were talking about. I strongly suspect that Dr De Meirleir has picked up on this. Giving small doses of rituximab is not 'prudent'. In order to break a cycle of autoantibody production even for a period of months you need complete depletion - both on theoretical grounds and based on experience in particular in lupus. Anything less than about 90% depletion tends to have no clinical benefit at all, as one would theoretically expect. The reasons are to do with complicated immunology. However, it is not too difficult to follow. If a self-controlling system has got into a vicious cycle then gentle actions are more likely to interfere with the remaining good functions of the system than hit the vicious cycle. If you blow gently at a snowball rolling down a hill you do not stop the snowball getting bigger, you just blow away the snow around it.

Moreover, the real dangers with rituximab are of post-infusion allergic reactions and pneumonitis and as far as we know these are UNRELATED to dose - they occur after the first infusion, even if small.

So giving small doses for 'prudence' is in my view stupid meddling. I also have reason to be angry about this.When I developed B cell depletion therapy for RA I thought it might do a lot of good but I realised that in the hands of stupid and irresponsible physicians it might do a lot of harm. We went through that with physicians in France and probably Belgium giving rituximab without monitoring adequately. The lesson was learnt but not without harm being done. I consider myself responsible at least in part for harm done by usage of the drug. As a result I am only too happy to act as an expert witness for the plaintiff in cases of negligence in relation to inappropriate use. The very last thing I, and also Oystein Fluge and Olav Meall, want to see in ME/CFS is usage by phsyciains who do not understand what they are doing. I sincerely hope that Dr De Meirleir is not playing around with it.

 

[Kati]

Moreover, the real dangers with rituximab are of post-infusion allergic reactions and pneumonitis and as far as we know these are UNRELATED to dose - they occur after the first infusion, even if small.

So giving small doses for 'prudence' is in my view stupid meddling. I also have reason to be angry about this.When I developed B cell depletion therapy for RA I thought it might do a lot of good but I realised that in the hands of stupid and irresponsible physicians it might do a lot of harm. We went through that with physicians in France and probably Belgium giving rituximab without monitoring adequately. The lesson was learnt but not without harm being done. I consider myself responsible at least in part for harm done by usage of the drug. As a result I am only too happy to act as an expert witness for the defence in cases of negligence in relation to inappropriate use. The very last thing I, and also Oystein Fluge and Olav Meall, want to see in ME/CFS is usage by phsyciains who do not understand what they are doing. I sincerely hope that Dr De Meirleir is not playing around with it.

Absolutely agreed. Nurses giving the infusions need to be aware of the protocol. Infusions should not occur if a doctor is not on the premises, and that staff is aware of infusion reaction procedures. When properly infused, Rituximab is safer than most chemo drugs. But staff must be ready for all eventualities.

Proper follow-up need to be done, and concurrent administration of immunosuppressants like prednisone need to be weighed carefully as it increases the risk of potentially life threatening infections.

As more biologics enters the field, very careful examinations of each drugs must be performed in terms of side effects and risks, because each one is very different in terms of mechanism of action and associated risk. Example: Enbrel is not Rituximab. rituximab is not belimumab, and so on.

 

[Marky90]

If you blow gently at a snowball rolling down a hill you do not stop the snowball getting bigger, you just blow away the snow around it.

That`s not only a great metaphor, but also one that is valid for how we must go about treating ME/CFS, whatever drug(s) that will prove to be the answer.

It`s a complex disease(s), that needs potent interventions.

 

[msf]

Prof. Edwards, would that also be the case if Ritux worked in ME through an anti-inflammatory effect rather than an anti-autoimmune one?

The same thing occured to me about the lack of a dose-dependent effect on hypersensitivity reactions. The only justification I could see for using a smaller dose, therefore, would be to ensure that the B cells weren´t fully depleted.

 

[barbc56]

That`s not only a great metaphor, but also one that is valid for how we must go about treating ME/CFS, whatever drug(s) that will prove to be the answer.

It`s a complex disease(s), that needs potent interventions.

Amen!

Edit. Added original metaphor.

Jonathan Edwards said: ↑
If you blow gently at a snowball rolling down a hill you do not stop the snowball getting bigger, you just blow away the snow around it

.

 

[Jonathan Edwards]

Prof. Edwards, would that also be the case if Ritux worked in ME through an anti-inflammatory effect rather than an anti-autoimmune one?

The same thing occured to me about the lack of a dose-dependent effect on hypersensitivity reactions. The only justification I could see for using a smaller dose, therefore, would be to ensure that the B cells weren´t fully depleted.

I am not sure what anti-inflammatory effect you are thinking of. Rituximab depletes B cells and does nothing else and B cells produce inflammation via antibodies and unwanted inflammation is pretty much associated with autoantibodies. However, there is a possibility that we have discussed in the past - that in ME the symptoms are due to antibodies that may not strictly be auto but may be tickling up central inflammatory signalling pathways for some other reason. (MS would be an example of 'bad antibodies' maybe not necessarily being autoantibodies.)

In this case the argument would seem to be much the same as for autoimmunity. The benefit in autoimmunity seems to come from the fact that autoantibodies are mostly produced by short lived plasma cells, which die off after rituximab leaving useful long lived ones. Maybe there are short lived plasma cells in ME making 'bad' but not 'auto' antibodies. In that case the logical thing to do is fully deplete B cells, otherwise you have a trickle top up of short lived plasma cells carrying on.

 

[msf]

What if Rituximab works in ME mainly by decreasing the level of proinflammatory cytokines in the body, but those cytokines are not being produced against autoantibodies, or ´bad´ antibodies, but rather are just part of an ineffective immune response to an infection?

Here is an example of how this might work, in an infection that gets a lot of attention around here: http://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0461-y

What if Rituximab has little negative effect in terms of reactivating/promoting the spread of an infection, and helps with the symptoms through an antiinflammatory effect? I noticed that someone posted a study of RA and Hep B in which there was little evidence of reactivation in most of the patients.

Of course, if it is used in this way, to reduce the amount of inflammation in the body, it is even more of a sledgehammer than if it is used to target autoantibodies.

 

[Hip]

However, there is a possibility that we have discussed in the past - that in ME the symptoms are due to antibodies that may not strictly be auto but may be tickling up central inflammatory signalling pathways for some other reason. (MS would be an example of 'bad antibodies' maybe not necessarily being autoantibodies.)

That is a very interesting concept: that ME and MS could be driven by such "bad antibodies."

Is there any specific research or literature that further details this concept of antibodies that are not quite autoimmune, but nevertheless interact with the immune system and ramp up inflammation?



When I was pondering on the vagus nerve / sickness behavior hypothesis of ME/CFS, it occurred to me that if there were autoantibodies that target and agonize the IL-1β and/or TNF-α receptors on the vagus nerve (these are the receptors that trigger sickness behavior in the brain), the activation of these receptors alone could produce many of the symptoms of ME/CFS.

The fact that we see evidence for autoantibodies to other vagus nerve receptors in ME/CFS (the muscarinic receptor autoantibodies found my Fluge and Mella and others) suggests that such IL-1β and TNF-α receptor autoantibodies might also occur.

In effect, what I am describing is an autoimmune version of the vagus nerve infection hypothesis of ME/CFS: instead of the vagus nerve IL-1β and TNF-α receptors being activated by an infection of the nerve and thereby triggering sickness behavior (Michael VanElzakker's theory), these receptors might instead be activated by autoantibodies.

 

[Gingergrrl]

@Jonathan Edwards is the original autoimmune dose that you developed a total of two infusions being one week apart?

 

[Jonathan Edwards]

What if Rituximab works in ME mainly by decreasing the level of proinflammatory cytokines in the body.

Because rituximab has no effect on cytokines. Small molecular mass drugs like steroids an anti-inflammatories do also sorts of strange things becuase, being very small, they bind tightly to a whole lot of different molecules. The binding site for rituximab is in comparison like a football pitch and the only thing that fits it at football pitch size is CD20 on B cells. So there is no plausible way that rituximab can work other than by killing B cells. B cells are not in themselves inflammatory cells. They do not occur in the inflammatory response because there job is to undergo natural selection in lymph nodes and then give rise to plasma cells (that have no CD20) that make antibodies that can mediate inflammation.

Basically there is no analogy with the sort of drugs in the quoted paper.