New German Trial for Rituximab? (High Dose)

[siobhanfirestone]

Hi all, its appears a German Dr, Dr Habets who is an Oncologist, is undertaking a trial (or just randomly treating its very hard to tell) with Rituximab in Long COVID and Me/cfs patients who test positive for GCPR aabs via bioassay (ie not ELISA). Its REALLY hard to fully understand what is happening and as it seems to be a private clinic it feels very sus, but im wondering what peoples thoughts are. I dont even know if this will result in legitimate data being published?
Here is what i can find;
https://habets-aachen.com/wp-content/uploads/2023/09/Stellungnahme-zu-Rituximab.pdf and his website is https://habets-aachen.com/
His basis seems to be two fold
1) retroactive studies showed GCPR patients are the ones who responded well in first trial
2) he doesnt think dose was enough in phase 3

His twitter posts (translated via google)
the trial/approach: Today we start with Rituximab therapy in patients with ME CFS and Post Covid. It takes a somewhat atypical form because we had severe side effects in one patient in the first two weeks after the first administration of 1400 mg. We will now divide it up, the therapy is carried out weekly with 350 mg subcutaneously for eight weeks. We then monitor the decrease in GPCR autoantibodies. If the decrease is sufficient, we continue the treatment as maintenance therapy every three months, initially for one year. Then further decision about continuing the therapy.

for dose he said: 1400 mg subcutaneously is equivalent to 1000 mg . This is the effective dose for autoimmune diseases.

in responce to fluge failing: The crucial error in the randomized Norwegian study times the maintenance therapy, which was limited to 500 mg In the small study it was 500 mg per square. We first have it tested at ERDE. The therapy controls with Elisa at IMD or biovis. We check beforehand whether there is activated EBV using EBV DNA PCR


If this is all being done privately and outside of a trial this feels like a huge amount of data going to waste tbh

 

[Jonathan Edwards]

This looks like total pseudoscience from my perspective as the person who invented this as a treatment for autoimmunity.

There is no good evidence that antibodies to GPCR have anything to do with ME.
He clearly does not understand the toxicity issues with rituximab so I would recommend people steer well clear of this.

 

[siobhanfirestone]

This looks like total pseudoscience from my perspective as the person who invented this as a treatment for autoimmunity.

There is no good evidence that antibodies to GPCR have anything to do with ME.
He clearly does not understand the toxicity issues with rituximab so I would recommend people steer well clear of this.

im sceptical as well and would say im sure the norwegians are trialing dara for a reason and the reason is that ritux didnt work

out of interest though why is it that you think the hard core chemo worked in some patients for the norwegian trial if its not something to do with antibodies and the immune system? i am certain the norwegians are trialing more drugs because they dont want me and lc patients to have to suffer from chemo which is horrid

in terms of aabs i think the recent finding of dr carmen schebebogen who is one of the main proponents actually shows it didnt correlate so i cant imagine its as simple as GCPR aabs no.

 

[Jonathan Edwards]

out of interest though why is it that you think the hard core chemo worked in some patients for the norwegian trial

I don't think we know that cyclophosphamide did anything, since we do not have a randomised double blind trial. Even if it did something it need not have been through B cellos antibodies since cyclo poisons pretty much everything. The patients with cancer may have had remission in cancer-related fatigue too.

It is quite possible that many PWME have an immune disturbance susceptible to cyclophosphamide but it cannot be a sensible drug to use.

 

[TheBassist]

This looks like total pseudoscience from my perspective as the person who invented this as a treatment for autoimmunity.

There is no good evidence that antibodies to GPCR have anything to do with ME.
He clearly does not understand the toxicity issues with rituximab so I would recommend people steer well clear of this.

Oh boy. Here we go. I wish her a lot of luck, so far it doesn’t sound pleasant https://twitter.com/user/status/1752250122228912283

 

[Marky]

I don't think we know that cyclophosphamide did anything, since we do not have a randomised double blind trial. Even if it did something it need not have been through B cellos antibodies since cyclo poisons pretty much everything. The patients with cancer may have had remission in cancer-related fatigue too.

It is quite possible that many PWME have an immune disturbance susceptible to cyclophosphamide but it cannot be a sensible drug to use.

Yeah, they didn't want to do a double blind trial because they thought the reported side effects seemed too big, especially concerns about the effect on fertility if I remember correctly

 

[RedFox]

Yeah, they didn't want to do a double blind trial because they thought the reported side effects seemed too big, especially concerns about the effect on fertility if I remember correctly

That's ridiculous. PwME should be allowed to decide what treatments they want. If it works but renders people infertile I would take it. I don't care because I never want children.

 

[Solstice]

That's ridiculous. PwME should be allowed to decide what treatments they want. If it works but renders people infertile I would take it. I don't care because I never want children.

If there was something out there that'd fix me up but made me sterile I'd bite their hand of. Can always adopt a couple of those little turds. Or at the age I'm at(40) any woman that I manage to attract will likely already have a few. That said, Cyclophosphamide does seem a bit like a horror-drug.

 

[siobhanfirestone]

Oh boy. Here we go. I wish her a lot of luck, so far it doesn’t sound pleasant https://twitter.com/user/status/1752250122228912283

Even non ME/CFs patients are VERY likely to get transiently worse as these Mabs kick in, hopefully her doctor is helping her through a likely short but intense flare. As we know this is a long term game, fingers crossed for her.

Cyclo clearly cant be blinded so yes, the data we have is the data we have. I will be doing it if the b cell approach i am currently taking does not work (ritux mixed with bort)

 

[Jaybee00]

That's ridiculous. PwME should be allowed to decide what treatments they want.

Yes of course. But @Marky was referring to the decision by Haukeland not to pursue further research on cyclo, which is a different issue.

 

[Marky]

That's ridiculous. PwME should be allowed to decide what treatments they want. If it works but renders people infertile I would take it. I don't care because I never want children.

I dont disagree. If I were to guess the results weren't convincing enough as well.

 

[Marky]

If there was something out there that'd fix me up but made me sterile I'd bite their hand of. Can always adopt a couple of those little turds. Or at the age I'm at(40) any woman that I manage to attract will likely already have a few. That said, Cyclophosphamide does seem a bit like a horror-drug.

Haha. The problem with Cyclo is that it's not a cure, so patients would relapse. I would guess you can't take Cyclo for many years before it starts causing some serious damage, not only to fertility.

 

[Jonathan Edwards]

Even non ME/CFs patients are VERY likely to get transiently worse as these Mabs kick in,

Do you actually have any evidence of your own to base that on? Or any published evidence?

I routinely followed up over 200 patients treated with rituximab, for half a dozen different diseases. I cannot remember a case of the original condition getting worse. There are certainly serious side effects but that is something different.

 

[siobhanfirestone]

Do you actually have any evidence of your own to base that on? Or any published evidence?

I routinely followed up over 200 patients treated with rituximab, for half a dozen different diseases. I cannot remember a case of the original condition getting worse. There are certainly serious side effects but that is something different.

for clarity not the condition, side effects of the mab that feel crap and similar to a flu.....and therefore similar to ME
just reports from patients i know who have takwn it, and reported side effects from infusions are here but many fold: https://www.rituxan.com/ra/treatment/side-effects.html

 

[siobhanfirestone]

Haha. The problem with Cyclo is that it's not a cure, so patients would relapse. I would guess you can't take Cyclo for many years before it starts causing some serious damage, not only to fertility.

i believe in the long term data melle published which was years iirc, the remissions patients were still doing very well and on the whole even better than the original ritx patients, placebo had the worse worsening as you can imagine

 

[EndME]

i believe in the long term data melle published which was years iirc, the remissions patients were still doing very well and on the whole even better than the original ritx patients, placebo had the worse worsening as you can imagine

The published follow-up data is for 4 years, which is long but possibly not sufficiently long enough from what I've gathered. I believe the unpublished follow-up data will be for 6 years. According to that 18% got back to normal healthy levels in the unblinded Cyclo trial, that is more than for both groups in the placebo controlled RTX trial, however it is also less than in the originial unblinded RTX trial if I recall correctly.

I actually wasn't under the impression that they'd given up on this end, especially on a possible role of long-lived plasma cells. They just can't do a placebo-controlled Cyclo trial because the effect isn't sufficiently large, the blinding of Cyclo is sufficiently hard due to it killing off everything (Cyclo trials aren't placebo controlled and in ME/CFS there is no useful control substance), there'll always be toxicity concerns and because it kills everything you don't learn what is involved and what isn't.

I was under the impression that they had moved on to Daratumumab and studying microcirculation.

 

[Jonathan Edwards]

for clarity not the condition, side effects of the mab that feel crap and similar to a flu.....and therefore similar to ME
just reports from patients i know who have takwn it,

OK, but in general the side effects of rituximab are nothing like ME. ME patients may well get PEM from the rigmarole of having an infusion, so I don't see that as to be blamed on the drug itself.

 

[Jonathan Edwards]

reported side effects from infusions are here but many fold: https://www.rituxan.com/ra/treatment/side-effects.html

That is an interesting document but if I remember rightly it was put out by Genentech at the time when rituximab was made available for RA. Genentech really didn't like the idea of rituximab being used in RA. I had to persuade them it was useful and get Roche to do the trial. I suspect the risk of litigation in the US threatened the lucrative market for lymphoma, where serious side effects could be brushed aside.

The text mentions the rare complications that occur in less than 0.1%. It actually misses the most important common problem which is sterile pneumonitis. The commonest side effect is a prickling throat, probably due ti effective activity in tonsillar tissue.

 

[Marky]

for clarity not the condition, side effects of the mab that feel crap and similar to a flu.....and therefore similar to ME
just reports from patients i know who have takwn it, and reported side effects from infusions are here but many fold: https://www.rituxan.com/ra/treatment/side-effects.html

I only had a very mild flu. I coordinated a group for people taking it privately. It was my impression that the side effects people reported actually were PEM due to overexertion cause of travelling.

 

[Sid]

The published follow-up data is for 4 years, which is long but possibly not sufficiently long enough from what I've gathered. I believe the unpublished follow-up data will be for 6 years. According to that 18% got back to normal healthy levels in the unblinded Cyclo trial, that is more than for both groups in the placebo controlled RTX trial, however it is also less than in the originial unblinded RTX trial if I recall correctly.

I know of a case who had ME/CFS and fibromyalgia for 20+ years, got cancer, received cyclo and was unexpectedly cured of ME/CFS in the process. This was years before the Norwegian rituximab and cyclo studies so probably not placebo/expectation bias. However, the symptoms returned 18 months later. Nonetheless, it's encouraging that even very long-term cases are reversible.