Effect of Rituximab in ME vs in other autoimmune diseases

[Adele]

The findings from the studies of Mella and Fluge so far suggests that Rituximab has a moderate to very good effect in around 2/3 of ME-patients. Out of that one can speculate about whether the remaining 1/3 might not have an autoimmune disease, or whether their autoimmunity is just of a kind that doesn't respond well to exactly this drug. An interesting question along these thoughts is of course how Rituximab affects patient-populations with a confirmed autoimmune disease. Would a response in 2/3 of the patient-population be similar to what one could find from a certain drug like Rituximab used e.g. in RA or MS? Or would one rather expect to find some response in everyone who receive the drug when autoimmunity is confirmed? I think I have read somewhere that Fluge and Mella continue their research by trying to find new ways of manipulating the immune system to help the non-responders - which of course suggests a hypothesis of finding autoimmunity also in the rest of the group. Any thoughts on this anyone? And does anyone know what treatments are being tried in the "non-responder"-group?

This really is exciting stuff and exciting times. And what a miracle it will be the day someone shows up with "the solution". For my next reincarnation I strongly consider becoming a medical researcher instead of a lawyer

 

[NK17]

Hi @Adele I couldn't agree more with you and your post, on any single possible level !

Everything that comes out of Mella and Fluge is music to my ears. These two are serious and profoundly dedicated doctors turned researchers and everything that will come out of their work will benefit PWME all over the world and other patients' population affected by other overlapping diseases.

 

[funkyqueen]

The findings from the studies of Mella and Fluge so far suggests that Rituximab has a moderate to very good effect in around 2/3 of ME-patients. Out of that one can speculate about whether the remaining 1/3 might not have an autoimmune disease, or whether their autoimmunity is just of a kind that doesn't respond well to exactly this drug.

My Internist Doctor told me, (in essence), that, in studies to demonstrate the efficacy of a molecule / drug for one disease, it was rare that percentages greater than 60% to 70% are found. All studies, all molecules / drugs, all mingled diseases .

In other words, and as that I understood, that it could be considered a response rate to a drug between 60% and 70% * ... would mean in fact amount to almost 100% efficiency.

* (Fluge & Mella 's published Studies respectively reported 67% and 64% of answerers ) ...)

I do not know if I express myself well

Professeur @Jonathan Edwards , I'd love your opinion on this, please ?

 

[Jonathan Edwards]

My Internist Doctor told me, (in essence), that, in studies to demonstrate the efficacy of a molecule / drug for one disease, it was rare that percentages greater than 60% to 70% are found. All studies, all molecules / drugs, all mingled diseases .

In other words, and as that I understood, that it could be considered a response rate to a drug between 60% and 70% * ... would mean in fact amount to almost 100% efficiency.

* (Fluge & Mella 's published Studies respectively reported 67% and 64% of answerers ) ...)

I do not know if I express myself well

Professeur @Jonathan Edwards , I'd love your opinion on this, please ?

60-70% is common for chronic diseases like rheumatoid arthritis or asthma but there are situations where more or less 100% response occurs, and also others where 10-20% occurs. I don;t think you can call 60-70% 100% really. I would be very surprised if all ME responded to B cell targeting because I doubt it is always B cell related.

 

[digital dog]

From what I understand the best responders will be people who have a family history of autoimmune diseases. That is why women tend to be better responders (and more women have ME).

I don't think, however, that they allowed people who have other autoimmune conditions on the trial but I would love to know what the patients family health histories were.

 

[BurnA]

From what I understand the best responders will be people who have a family history of autoimmune diseases. That is why women tend to be better responders

From what I understand there is no evidence for this.

 

[Marky90]

From what I understand there is no evidence for this.

Nope there`s not, if you check the data. There is however more women responders, quite simply because there are more women than men in the trials.

 

[Biarritz13]

Is there any evidence concerning the response and the trigger?

 

[BurnA]

Is there any evidence concerning the response and the trigger?

Nope, there is no evidence for anything - it's something we all want to know. The only data we have is in the open label phase 2 trial, all the information is there however its impossible to draw any conclusions.

The UCL team, as part of iime research, are trying to identify who might respond but no news on that.

 

[Biarritz13]

Thank you BurnA.

 

[BurnA]

60-70% is common for chronic diseases like rheumatoid arthritis or asthma but there are situations where more or less 100% response occurs, and also others where 10-20% occurs. I don;t think you can call 60-70% 100% really. I would be very surprised if all ME responded to B cell targeting because I doubt it is always B cell related.

Is it possible that patients have a b cell related disease ( same as whatever the 60% phase 2 responders have ) but dont respond to rtx ?

So could the prevalence of this b cell related disease be greater than the response rate ?

 

[deleder2k]

As far as I understand professor Fluge, clearing out memory B-cells could be a winning formula.

 

[Biarritz13]

I am curious what would be the result of the rituximab + fasting since it lowers the white blood cells on its own.

 

[perrier]

60-70% is common for chronic diseases like rheumatoid arthritis or asthma but there are situations where more or less 100% response occurs, and also others where 10-20% occurs. I don;t think you can call 60-70% 100% really. I would be very surprised if all ME responded to B cell targeting because I doubt it is always B cell related.

If the illness is not always B cell related,would this mean that we are speaking about different illnesses and patients have been lumped in under one diagnosis? And forgive the ignorance of my question, but how can one tell if the problem is B cell related? Thank you

 

[Jonathan Edwards]

If the illness is not always B cell related,would this mean that we are speaking about different illnesses and patients have been lumped in under one diagnosis? And forgive the ignorance of my question, but how can one tell if the problem is B cell related? Thank you

I think it is very likely that patients with different causes are lumped under one diagnosis. However, if the diagnosis is intended to refer to an effect, just as it is for diabetes or high blood pressure (both of which have many causes) then that would not be unusual.

We can only tell if a problem is B cell related for sure if it responds to B cell targeted treatment. But if we can ind evidence of B cell misbehaviour in the form of autoantibody or other abnormal antibody production then that would give a strong suggestion.

 

[funkyqueen]

60-70% is common for chronic diseases like rheumatoid arthritis or asthma but there are situations where more or less 100% response occurs, and also others where 10-20% occurs. I don;t think you can call 60-70% 100% really. I would be very surprised if all ME responded to B cell targeting because I doubt it is always B cell related.

I share with you the same feeling, Prof. Edwards
Thanks for yours explanations

 

[digital dog]

Im sorry but what I wrote was inaccurate (brain fog). I meant to say that they think ME is autoimmune in nature because of more women having it and more people coming from autoimmune riddled families.

I read this but Im not saying it is correct (did anyone else read this?) What I posted before was not what I read and was definitely incorrect.

 

[leokitten]

Efficacy, or lack thereof, of a particular drug doesn't necessarily disprove the hypothesis you are testing by using that drug.

As I wrote in another thread take the example of relapsing-remitting (RRMS) and primary progressive MS (PPMS). Rituximab has impressive efficacy in RRMS in clinical trials and in practice. Yet in PPMS, which is typically a more severe disease than RRMS, rituximab failed in clinical trials. The MS community thought for a while that these diseases are possibly fundamentally different with different mechanisms. However, recently the more potent CD20 drug ocrelizumab has shown far better efficacy in PPMS in clinical trials. Both rituximab and ocrelizumab work on the exact same principle, they deplete B-cells.

So long story short just because rituximab doesn't work in a subset doesn't mean we can definitively say that they have a completely different disease mechanism.