Attack on Lipkin/Hornig and Fluge in a medical magazine

[Gijs]

I forgot; i would never use RTX if you are longer sick then 3 years because the data of Lipkin shows the immunesystem is burnout.

 

[deleder2k]

The Rituximab trials are interesting, but they still don't imply autoimmunity. The overactivity of B-cells and swelling of lymph nodes could be simply because an impairment of lymphatic functioning and/or an increase in extra-cellular debris from chronic tissue damage (physically caused, like tissue injury, not autoimmune).

Plus from what I've heard, Rituximab doesn't seem to be curative, as many just relapse. I don't know what the rate is or the quality of improvement, though. Does it just temporarily reduce cytokines or can it create a lasting change? Guess they'll find out.

The Rituximab trials do imply autoimmunity. How can I say that? It is because of the delayed effect. It usually takes 3 months before one see any effect at all. B-cells die almost immediately. That rules out a B-cell virus. As months go by antibodies start to die, and new ones are not being produced anymore. The reason it works is almost certainly the fact that autoantibodies die out.

Rituximab looks curative for 50% of those who gets 6 infusions. Several patients has been in remission for many years without RTX now.

You also say that:

There is absolutely no reason to believe something is wrong primarily with the immune system in CFS/ME

Are you serious? Here is IOM's conclusion:

Sufficient evidence supports the finding of immune dysfunction in ME/CFS.

 

[deleder2k]

I must say that i think there is nothing primarly wrong with our immune system either. I agree with this doctor at some point, sorry. I would never use RTX as this moment ( according the scienetific data) as a patiënt. My mother used it an she almost died after 6 infusions, she did get a terrible shock! Very dangerous. The problem of ME is in the brain.

Brain?? And what proof do you have?

 

[A.B.]

The Rituximab trials are interesting, but they still don't imply autoimmunity. The overactivity of B-cells and swelling of lymph nodes could be simply because an impairment of lymphatic functioning and/or an increase in extra-cellular debris from chronic tissue damage (physically caused, like tissue injury, not autoimmune)

There has been discussion on this. From my memory the conclusion was that autoimmunity is the most likely explanation for the observed results.

 

[Sidereal]

My mother used it an she almost died after 6 infusions, she did get a terrible shock! Very dangerous.

Was your mother treated with rituximab for ME/CFS or another illness?

 

[Gijs]

Brain?? And what proof do you have?

PET scan Japanese study and the Stanford MRI study. It must be replicated that will be done soon.

 

[Gijs]

The Rituximab trials do imply autoimmunity. How can I say that? It is because of the delayed effect. It usually takes 3 months before one see any effect at all. B-cells die almost immediately. That rules out a B-cell virus. As months go by antibodies start to die, and new ones are not being produced anymore. The reason it works is almost certainly the fact that autoantibodies die out.

Rituximab looks curative for 50% of those who gets 6 infusions. Several patients has been in remission for many years without RTX now.

You also say that:


Are you serious? Here is IOM's conclusion:

In Germany they did a study with RTX (not publiced yet) it didn''t work at all. Only POTS patiënts will be benefit from RTX because it is ''proven'' that this disorder is autoimmunity against receptors.

 

[Gijs]

Was your mother treated with rituximab for ME/CFS or another illness?

Another illness.

 

[Jonathan Edwards]

The bias on these forums is pretty staggering sometimes. Mads Reimer makes some good points. There is absolutely no reason to believe something is wrong primarily with the immune system in CFS/ME. There are certainly differences in cytokines and NK cells and whatever else, but to think their manipulation would fix anything is still just shooting in the dark.

Of course they can try, but it does seem stupid and maybe even unethical to try such a damaging drug. Some side-effects of Cyclophosphamide: nausea, vomiting, stomach ache, diarrhea, joint pain, unusual tiredness tiredness or weakness, and lethargy.

What the fuck are they thinking?

I agree that there is bias all over the place but I think there may be a more constructive way out of this one. Dr Reimer contacted me and I think he is at least interested in comments.

Reimer makes some valid point but they are not new to us and I think the problem is that they are gathered up in an unduly negative (or at least unhelpful) overall interpretation. And we cannot say 'There is absolutely no reason to believe something is wrong primarily with the immune system in CFS/ME. ' There are lots of reasons to think there might be something wrong in at least a proportion of cases (which allows others to come under Gijs's reasonable analysis). Lots of people have found strange NK cell data and historically there has been evidence for an increase in autoantibodies. I am not sure that targeting the NK cells will help but to think that manipulation migh tfix things is not shooting in the dark if we already have a trial suggesting it might work. We are just shooting in bad light.

On the other hand, to be honest, I d not think we should accept the IOM statement 'Sufficient evidence supports the finding of immune dysfunction in ME/CFS.' because it is too strong the other way and tends to imply (although not explicitly) that immune dysfunction is general to all cases.

Sensible progress requires accepting a high degree of uncertainty and assessment of probabilities that research strategies may be fruitful. I am not at all sure that Dr Fluge and Dr Mella are convinced that even a subset of ME/CFS is autoimmune. In our discussions we have talked of the initial observations suggesting that a subset is 'B cell dependent'. The kinetics of the phase II response does suggest that this is because of 'antibody dependence' but that still leaves room for some mechanism we do not understand that is antibody mediated but not autoimmune. People tend to try to run before they can walk. We are still uncertain of the basic mechanisms even of the common 'autoimmune diseases'. The Norwegians always take the view that 'we have these data which suggest these possibilities...' and no more.

Cyclophosphamide causes nasty symptoms for a day or two but oncologists and rheumatologists know that it can save lives and remove symptoms for years. I used for RA, but it turned out to be redundant. To suggest it cannot be appropriate for ME/CFS is effectively to deny that ME/CFS causes major disability or distress. It is a bit like saying ECT is not suitable for psychotic depression. I am very glad that ECT brought my wife back to life. The alternative was visiting a cachectic ghost in a prison cell twice a week for thirty years.

So I think everybody can be right to a degree. What I think is a pity is to criticise research work without have met the scientists who are involved, or at least seen the way they present their work, and without a good level of knowledge in the technology of the field. We used to live in a world where nobody commented in public at all. Now we live in a world where comment is popular - I think that is a good thing but commentators need to be prepared to back up their point of view.

 

[Bob]

The problem of ME is in the brain.

We'd all agree that ME affects the brain, to varying degrees, but I think many would question, or disagree with, the assertion that THE problem with ME is in the brain. Perhaps this reflects the fact that many of us have different subjective experiences of the illness, and that there is a degree of heterogeneity in patients who receive an ME or CFS diagnosis? Patients who regularly experience flu-like symptoms may interpret it as indicating a primary immunological disease. Patients who experience primarily cognitive symptoms may interpret it as indicating a neurological disease. My personal bias is that the answers do not lie solely within the brain but lie primarily within the immune system which affects the nervous system and the brain (e.g. immune cells within the brain.) And I think that mitochondrial dysfunction may play a central role: mitochondrial dysfunction could potentially be caused by immunological abnormalities or it could cause immunological and neurological dysfunction.

 

[Bob]

I forgot; i would never use RTX if you are longer sick then 3 years because the data of Lipkin shows the immunesystem is burnout.

That's a hypothesis/observation that can easily be tested in the rituximab trials.

 

[Blue]

In Germany they did a study with RTX (not publiced yet) it didn''t work at all.

No, there wasn't any study. There were a couple of patients who received RTX as an Off-Label treatment. It's hard to draw any conclusions from that. Only clinical trials will tell.

 

[deleder2k]

I think that's an interesting hypothesis/observation that needs to be tested in the rituximab trials.

Rituximab has made several patients healthy again including dr. Maria Gjerpe who had ME for 20 years.

 

[Gijs]

Rituximab has made several patients healthy again including dr. Maria Gjerpe who had ME for 20 years.

Placebo effect deleder? Just kidding

 

[deleder2k]

Placebo effect deleder? Just kidding

Hehe. Some who got better was in a double-blinded RCT: B-lymphocyte Depletion Using Rituximab in Chronic Fatigue ...

 

[alex3619]

I am not convinced the problem is autoimmunity, but I am not convinced it isn't either. An autoimmune hypothesis and a brain hypothesis are not necessarily mutually contradictory either. An immune attack on the brain, or tissues closely associated with the brain, could potentially drive the brain problems. Non cytopathic viral pathogens could potentially drive the autoimmunity. Its a mess.

The autoimmune hypothesis is a good one but as yet unproven. I will be very pleased to see more science on both immune issues and brain pathology.

Let me remind people the most common trigger for ME is a viral infection, and the most common pathogens (according to a study I don't recall the name of right now, reviewed here on PR several years back) also infect B cells.

We are still trying to understand the immune system. We are even further from figuring out the brain. I want to see all reasonable avenues investigated until we have answers. For now that includes Rituximab and neuroimaging.

Indeed I just got the forms to go for a qEEG myself. Unlike CPET or TTT its relatively risk free ... provided I can find the energy to get there.

 

[Bob]

Rituximab has made several patients healthy again including dr. Maria Gjerpe who had ME for 20 years.

Thanks deleder. Maria Gjerpe's response to rituximab clearly indicates that long-term patients can respond to rituximab.

 

[Bob]

No, there wasn't any study. There were a couple of patients who received RTX as an Off-Label treatment. It's hard to draw any conclusions from that. Only clinical trials will tell.

In the Mikovits/Bieger video, Dr Bieger said that they'd prescribed rituximab to 10 patients. None of the patients experienced an improvement and two experienced deterioration. As you say, I was under the impression that this was off-label prescription rather than a clinical trial. It would be helpful to understand why they're getting different results to Fluge and Mella. They might be using a different diagnostic/selection criteria, or they might have used different doses and different infusion time intervals to Fluge and Mella. Buy it's the clinical trials that carry the weight in terms of the evidence. The off-label prescription anecdotes are interesting, but they don't tell us much in themselves.

 

[alex3619]

It would be helpful to understand why they're getting different results to Fkuge and Mella.

Sometimes things like this can lead to new understanding. Recruitment criteria, different protocols, different complications ... when this is examined by those involved sometimes they find out something new.

However with 10 patients on a therapy that can take more than 3 months to kick in, and only about a 70% success rate (I don't think its 66% any more, but I could be wrong) could be due to these factors plus chance.

Indeed, any small study could be due to chance factors. That is why the phase 3 trial is necessary. If this gets a positive result, as expected, it is much less likely to be due to chance. If its then replicated by the UK study then the robustness of the finding would be strong.

If however the Norwegian study and the UK study are in conflict then there is a problem and there will be many late nights trying to figure out what happened.

 

[Snow Leopard]

There is absolutely no reason to believe something is wrong primarily with the immune system in CFS/ME.

Versus what? Genetic disorders? Chronic infection? Please offer a better hypothesis if you disagree with this one.

It is these studies sorts of studies that will help demonstrate whether there is such a thing wrong with the immune system or not.