Phase III Rituximab Trial - News

Scarecrow said:
@Jonathan Edwards Do you recall saying on PR that Jo Cambridge's team had identified an abnormality in B cells that looked like the opposite of autoimmunity?

You weren't able to tell us more at the time but did anything ever come of that?
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I think this was about something called Vh4 heavy chain usage, which came up as opposite. I have not heard more from Jo on this. It may not have proved consistent.
 
Justy said:
Whoop whoop! If true - great news. I always thought there would be a third who might respond.

Do please Jorgen Jelsted's Blog post about it. He talks about low response rates in Lupus studies, a disease known to involve B cells. It didnt turn out to be the hoped for treatment in Lupus at all. So, it doesnt mean something serious isnt going on, or that we dont have autoimmune issues. It will be interesting to see what they did learn from the study...
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Responses in lupus are actually high (remember I introduced rituximab for lupus). The problem with rituximab in lupus is that the initial company sponsored trials excluded anyone with significant disease. The design shot itself in the foot. Rituximab is widely used lupus.

Failure to respond to rituximab does exclude autoimmunity. Scleroderma does not respond much. But this result really takes away the main reason for thinking that the illness is often autoimmune.
 
Perrier said:
These are, are they not Dr Edwards, areas of research? Are any meds/ treatments being looked at?
RTX disappointment is huge, as you know, because folks and younger people thought, I'll scrimp my pennies together and get the RTX and get my life back.
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Yes, areas of research. And that is chiefly hoe F&M saw rituximab, rather than as an instant treatment. Things take time I am afraid.
 
Jonathan Edwards said:
But I do not think there is any reason to do further rituximab trials in ME. We need to follow other leads.
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Thanks.

General query, do you think the very original responders ( cancer patients) may actually have responded, but to something different in their chemotherapy ? Or any thoughts on this ?

It's unlikely placebo played a part in those patients I would say.
 
BurnA said:
Thanks.

General query, do you think the very original responders ( cancer patients) may actually have responded, but to something different in their chemotherapy ? Or any thoughts on this ?

It's unlikely placebo played a part in those patients I would say.
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A true placebo response is only one of several reasons why people get better following treatments. I think it most likely that the original responses do not tell us anything useful about ME. They may have had immune dysfunction associated with lymphoma. The time course of immune dysfunction does not alaways follow the lymphoma in an obvious way so may appear to be a separate illness.
 
Sunshine3 said:
@Jonathan Edwards yet, there seems to be reasonable response to cyclophosphamide if they have moved onto stage B of the CycloME trial, giving it to the more severe patients. Would that not indicate autoimmunity for a subset?
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The problem with cyclophosphamide is that you cannot blind it because of the side effects. So the cyclo studies alone are not solid evidence.
 
Jonathan Edwards said:
A true placebo response is only one of several reasons why people get better following treatments. I think it most likely that the original responses do not tell us anything useful about ME. They may have had immune dysfunction associated with lymphoma. The time course of immune dysfunction does not alaways follow the lymphoma in an obvious way so may appear to be a separate illness.
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This sort of situation has been playing on my mind.

It's tough for us to take the news that the trial was negative but we have to accept the facts.

What bothers me is that there is going to be an admittedly very small percentage of pwME who have been misdiagnosed and confined to our little wastebasket without extensive testing. The adage "if you hear hoof beats, think horses" is all very well but if you don't actually take a look, you might miss the funny stripy creature disappearing over the horizon.

Do we need to push for more comprehensive investigation in the revised NICE guidelines?

How many times do we hear of someone formerly diagnosed with ME/CFS who finds out that something else was wrong all along and they are now getting treatment? It's tragic for everyone who has an ME/CFS diagnosis but how wasteful to lose years of your life on a misdiagnosis.
 
Isn't PEM exclusive to ME. If you don't get pem, you don't have ME. I don't understand confusion about who has or hasn't the disease. I could diagnose it and I ain't a doctor. No doctor diagnosed me until I diagnosed myself...the crashing was key plus the energy depletion. For people with ME, it is one disease with varying symptoms just like MS patients vary in their symptoms. The notion that ME is an umbrella over a number of different diseases makes no sense to me. I had acute onset, I hardly got struck down with a load of different illnesses at the same time. What we so need to find is what the hell is driving the illness. It always seemed to me that it was immune dysfunction as immune system never settled back after trigger.
 
Sunshine3 said:
Isn't PEM exclusive to ME. If you don't get pem, you don't have ME.
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Without getting into a prolonged discussion about various criteria, yes and no. ME/CFS (CCC) does, CFS/ME (NICE) does, ME (ICC) does, SEID (IOM - clinical only) does, CFS (Fukuda/CDC1994) doesn't, [CFS (Oxford) doesn't but who cares, it's nonsense and for research only].

There must be a lot of people out there diagnosed under Fukuda who don't have PEM.

Post Exertional Malaise and/or Fatigue is also something of a grey area (CCC and NICE).
 
Scarecrow said:
Without getting into a prolonged discussion about various criteria, yes and no. ME/CFS (CCC) does, CFS/ME (NICE) does, ME (ICC) does, SEID (IOM - clinical only) does, CFS (Fukuda/CDC1994) doesn't, [CFS (Oxford) doesn't but who cares, it's nonsense and for research only].

There must be a lot of people out there diagnosed under Fukuda who don't have PEM.

Post Exertional Malaise and/or Fatigue is also something of a grey area (CCC and NICE).
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Well if they don't have PEM....they don't have ME. PEM is the crucifying part of ME that restricts our lives so much. I know any researcher with any knowledge of ME would not be using Oxford Criteria, that should be binned long ago.
 
Over your last few posts you seem to be assuming that those with PEM must have ME, this may not be a valid assumption, especially given the confounding influence that some people seem to have been making the reverse assumption, when told they have ME.

PEM is, in one sense, just a series of words, who is to say it means the same to all.
 
Sunshine3 said:
Well if they don't have PEM....they don't have ME. PEM is the crucifying part of ME that restricts our lives so much. I know any researcher with any knowledge of ME would not be using Oxford Criteria, that should be binned long ago.
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Yes but the crucial thing is that even though I was careful to use ME, CFS, ME/CFS and CFS/ME appropriately in this instance, terms are commonly used interchangeably.
 
Sunshine3 said:
Well if they don't have PEM....they don't have ME
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Even if we confine the definition of ME to people who have PEM (which I think we should do), and even if we define PEM very carefully, I think it is still possible that there could be more than one biochemical pathway that leads to rapid energy depletion and slow energy recovery which in turn leads to PEM.

If there's one thing that has really come home to me in all the biomedical studies I've read and tried to understand in relation to ME it is just how complex biochemistry and cell functions are.

So I still think it's possible that ME defined with PEM could be a group of conditions with different biochemical malfunctions, rather than a single one, and that therefore one treatment is not likely to help all of us.
 
Perrier said:
Watching a family member very closely, I see PEM with any exertion: mental, physical, emotion,cognitive. Depending on the intensity of the exertion, the PEM comes immediately, or a day after. It lasts very long, from a day or two until two weeks or more. PEM is also often present non stop, if our beloved tries to do minimal activities not to go insane: buy some thing on line, read, etc.

She has PEM, OI, flu feeling almost non stop, sick feeling, toxic feeling, weakness.

However, I spoke with a CFS/ Lyme doctor with decades of experience whom I'll leave unnamed who told me he doesn't think PEM is specific to this illness. I was not in a position to question further. But he went on to say other illnesses also have this. Is this true?

The obvious question: do cardiac patients get it?

I'm so heartbroken by the lack of diagnostics, lack of help, lack of treatments. It's like living in a time of TB consumption, before antibiotics.
I think of young John Keats often and his dying in Italy, and his unrealized personal life with Fanny Brawne. Now my daughter is in the identical agony, so is Whitney, so is Tom C., and thousands of other young people.
When will there be some help? Time is not on our side...
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Ive spent time on Lupus, MS, thyroid and Lyme boards in an attempt to get to the bottom of my ilness and a lot of people with htose illnesses report something similar to PEM.

In terms of M.E and autoimmunity - of course quite a few of us have positive ANA titres, which have been brushed off by medical professionals. Im also keen to find out if the EDS/MCAS subset (group?) is different and if we actually have a different disease? Having said that my illness meets all criteria of M.E and looks like M.E and feels like M.E, without the severe pain symptoms some others have (i do get pain, its just not a major part of my illness).
 
Jenny TipsforME said:
I think we need to allow ourselves to feel the disappointment but this quote in the Invest in ME response is one to remember

we-must-accept.png


One day the research will get there but ok to :cry: today because it isn’t imminent

Re different phases:
Do we think there’s a placebo/demand characteristic type thing going on? If they were expecting positive results up until the unblinding it perhaps points to that? Did people in the placebo arm also respond?

But I always thought placebo was unlikely in the first two phases because of the weird delayed response, which I don’t think participants would know to expect. Need to wait for more info.

I guess my question is: does this work at a biological level for fewer pwme than we hoped OR was it a false positive that it worked in the previous studies?

Will other studies now not go ahead? @Jonathan Edwards @Jo Best
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Hi @Jenny TipsforME yes I agree with your good point about the delayed response in the Phase II trial,

Invest in ME Research commented on Facebook -

We would caution that nothing is certain yet. We hope to meet with the researchers and there are still grounds for optimism. One of the reasons that an early statement was made by the Haukeland team was to avoid patients going for treatment outside of clinical trials and with unselected patients . One of the reasons for the delay in the UK trial of this drug has been due to the desire to find likely responders and it is this caution that the Norwegian researchers have brought out in their results. So we await more news. Stay hopeful until we hear more.
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That Facebook post links to their statement: http://www.investinme.org/IIMER-Newslet-1711-03.shtml - extract below -

We have an excellent research team in Norway which has served the ME patient community and their families with honesty, integrity, professionalism, determination and an empathy which had never been seen before in this field.

We have established good working relationships between the Norwegian researchers and the UK Centre with input from UCL and UEA/Quadram Institute.

We have data now – more than before.

We have research which IiMER has established and a foundation for the Centre of Excellence for ME.

We have international collaboration in research into ME that will continue.

And we have new plans – already in the making.

The researchers from Haukeland will give more detail on their results and publish a paper or two which will benefit all studying ME.

For us, we have invited the Haukeland team to Norwich to discuss the way forward.

We remain positive. Another setback, another day.

We have already been in discussion with our advisors and with the Norwegian team and we will meet to clarify the best way forward in the near future with our major funder and researchers.

We still have much good research being funded and being planned and feel our stategy is, and will pay off and lead to the most rapid route to finding cause(s) of ME and effective treatments.

http://www.investinme.org/IIMER-Newslet-1711-03.shtml
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