New Rituximab ME/CFS open-label phase II study with rituximab maintenance treatment

[Jonathan Edwards]

Well, I learned a new word today.

I hoped the spellchecker was right when it didn't give me a red line.

 

[perrier]

Is there some way to summarize what sort if patient responds to RTX?

What sort of symptoms did these patients have?

Were they " classical" CFS presentation: PEM, OI, gut issues, sleep issues, severe weakness, toxic feeling. Flu feeling, adrenal insufficiency, cognitive issues.

 

[Jonathan Edwards]

Is there some way to summarize what sort if patient responds to RTX?

What sort of symptoms did these patients have?

Were they " classical" CFS presentation: PEM, OI, gut issues, sleep issues, severe weakness, toxic feeling. Flu feeling, adrenal insufficiency, cognitive issues.

As far as we know there are no pointers to who responds. All that has been suggested is that very severe cases may not be the best responders.

 

[panckage]

As far as we know there are no pointers to who responds. All that has been suggested is that very severe cases may not be the best responders.

What about the lady in video? She seemed to be very sure that the responders had certain measurable differences as compared to those who didn't. Was she just making hypothesis' or did she know what she was talking about?

 

[A.B.]

What about the lady in video? She seemed to be very sure that the responders had certain measurable differences as compared to those who didn't. Was she just making hypothesis' or did she know what she was talking about?

She gets basic things very wrong. I think she is just saying whatever sounds good at the moment.

 

[Riley]

What about the lady in video? She seemed to be very sure that the responders had certain measurable differences as compared to those who didn't. Was she just making hypothesis' or did she know what she was talking about?

The lady in the video is Dr. Judy Mikovits. That's all I'm going to say about that.

I would encourage you to read the previously linked discussion of that video.

 

[perrier]

As far as we know there are no pointers to who responds. All that has been suggested is that very severe cases may not be the best responders.

I have to ask: what is really a severe case?

Someone who is always bed bound? Someone who is primarily house bound, like Laura Hillenbrand?

Everyone that I know looks très très souffrante : sure sometimes they are a bit better, but I don't know any young person with this who is on a stable platform.

 

[Bob]

I have to ask: what is really a severe case?

A very severe case is someone who is permanently bed bound, unable to take care of themselves, often needing a stimulus-free environment (i.e. darkened room etc.) See the video of Whitney Dafoe and his family for an example.

A severe case is someone who is bed bound or almost entirely bed bound or sofa bound, unable to leave the home except for exceptional circumstances.

A moderate case is someone who is mainly house bound, but can walk or move around the home and can leave the home occasionally or regularly for short periods.

Obviously there are fluctuations for each individual, and each label (mild, moderate, severe etc) doesn't paint a complete picture of each individual. Everyone manages their health in their own way, and different people have different symptoms to deal with. i.e. some are more affected by brain fog and cognitive or neurological issues than others, whereas some may have more pain than others. Some may have more joint pain and joint inflammation than others. And some may have more orthostatic intolerance issues than others. etc.

 

[BurnA]

As far as we know there are no pointers to who responds. All that has been suggested is that very severe cases may not be the best responders.

Can it be determined or concluded that the responders have an autoimmune disease ?
Could it be possible some non responders also have an autoimmune disease but just don't respond for some reason ?
In other words could rituximab work in a subset of the subset of ME/CFS patients with an autoimmune dysfunction ?

 

[Bob]

Can it be determined or concluded that the responders have an autoimmune disease?

Autoimmunity seems to be the best hypothesis we have so far, based on the time it takes for patients to respond to rituximab. Until new evidence comes to light, that's the best we have to go on.

Could it be possible some non responders also have an autoimmune disease but just don't respond for some reason?

I think so. Not all rheumatoid arthritis patients respond to rituximab in the same way, as far as I understand. Also, I think I read (but maybe my brain has failed me, and maybe I'm inventing this) that Fluge and Mella will be looking out for responders with an even greater time delay in the phase iii trial.

 

[BurnA]

Autoimmunity seems to be the best hypothesis we have so far, based on the time it takes for patients to respond to rituximab. Until new evidence comes to light, that's the best we have to go on.


Yes. Not all rheumatoid arthritis patients respond to rituximab in the same way.

I wonder if @Jonathan Edwards can add anything ? can anything be learnt from RA in that it is an autoimmune disease yet different patients repsond to different treatments ? Could there me any similarities to ME/CFS or could it explain why some patients respond and others don't despite similar symptoms?

 

[BurnA]

I wonder if @Jonathan Edwards can add anything ? can anything be learnt from RA in that it is an autoimmune disease yet different patients repsond to different treatments ? Could there me any similarities to ME/CFS or could it explain why some patients respond and others don't despite similar symptoms?

Would the onset of symptoms be more gradual than sudden if autoimmunity is the issue ?
Is there any relationship between the duration for response to kick in ( typically 4-6 months) and length of time for symptoms to develop in the first place ?

 

[Bob]

Could there me any similarities to ME/CFS or could it explain why some patients respond and others don't despite similar symptoms?

ME (even using CCC or ICC) may be heterogeneous because we don't have any biomarkers that can confirm or refute its heterogeneity or homogeneity. I think Jonathan Edwards has said that rheumatoid arthritis is heterogeneous, but I'm going from my very unreliable memory.

 

[Bob]

Would the onset of symptoms be more gradual than sudden if autoimmunity is the issue?

ME has various onset patterns. It's not always clear to the patient exactly when the illness started. And I believe that other autoimmunity issues can first present themselves gradually or suddenly.

Is there any relationship between the duration for response to kick in ( typically 4-6 months) and length of time for symptoms to develop in the first place ?

Do you mean in relation to ME or other illnesses? For ME we don't have enough data, as there have only been two or three small trials. And I don't think we have any data in relation to your specific question.

 

[Jonathan Edwards]

Would the onset of symptoms be more gradual than sudden if autoimmunity is the issue ?
Is there any relationship between the duration for response to kick in ( typically 4-6 months) and length of time for symptoms to develop in the first place ?

The problem with drawing parallels within autoimmunity is that each autoantibody produces its particular disease in a completely different way, so there are almost no rules. And since autoantibodies accumulate by a gradual process of expansion of B cell clones over many years the disease onset can be sudden or gradual. Moreover, the susceptibility of autoantibody producing cells to rituximab varies so response varies.

 

[Valentijn]

Would the onset of symptoms be more gradual than sudden if autoimmunity is the issue ?

In the case of Type I Diabetes (autoimmune), the apparent onset is pretty sudden. There might be something going on before it's noticeable, but it can go from "feeling normal" one week, to "sick as a dog" the next week, to "in the hospital getting stabilized" for the following week.

So sudden onset seems like it shouldn't rule out autoimmune disease.

 

[BurnA]

The problem with drawing parallels within autoimmunity is that each autoantibody produces its particular disease in a completely different way, so there are almost no rules. And since autoantibodies accumulate by a gradual process of expansion of B cell clones over many years the disease onset can be sudden or gradual. Moreover, the susceptibility of autoantibody producing cells to rituximab varies so response varies.

OK so if i understand correctly, even if it is an autoimmunity disease, rituximab may or may not be effective depending on the patient even if the both have the same problem?
How would this relate to the work in UCL ? Is their focus on finding an autoimmune biomarker or finding a rituximab response biomarker ?

 

[Jonathan Edwards]

OK so if i understand correctly, even if it is an autoimmunity disease, rituximab may or may not be effective depending on the patient even if the both have the same problem?
How would this relate to the work in UCL ? Is their focus on finding an autoimmune biomarker or finding a rituximab response biomarker ?

There are often several reasons for doing any particular experiment in science so there may be no specific answer to your last question. The focus is in getting a handhold of whatever sort that might get us towards an effective treatment. And the methodology is dictated by what one can measure.

 

[beaker]

[

I have to ask: what is really a severe case?

Someone who is always bed bound? Someone who is primarily house bound, like Laura Hillenbrand?

Everyone that I know looks très très souffrante : sure sometimes they are a bit better, but I don't know any young person with this who is on a stable platform.

Here is David Bell's Scale that is often used as guideline.

It was expanded upon by The Hummingbird Foundation for ME
(Byron Hyde's group)

Others have expanded and adapted it.(He first published it in the early 90s)
But At least these will give you an idea at how most MECFS docs look at it. I've been in studies that have used it along w/ other measures of functioning.

 

[perrier]

[


Here is David Bell's Scale that is often used as guideline.

It was expanded upon by The Hummingbird Foundation for ME
(Byron Hyde's group)

Others have expanded and adapted it.(He first published it in the early 90s)
But At least these will give you an idea at how most MECFS docs look at it. I've been in studies that have used it along w/ other measures of functioning.

Thanks. Yes, I reminder the Bell scale from way back. Of course, the issue is that the illness is not stable,there are somewhat better hours and days and then horrific ones.

I have trouble understanding relapses. Does it mean B cells increase in those dreadful periods. I don't have a scientific background,so please overlook the naive questioning.