Trial Report Plasma cell targeting with the anti-CD38 antibody daratumumab in ME/CFS -a clinical pilot study, 2025, Fluge et al

neophyte32 said:
It s my last hope... What do we have in the near future besides daratumumab? SequencEM won't be available for at least five years, and it won't be a treatment... we have nothing.
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The thing I have my eye on other than dara is the JAK inhibitor trials. If members here are right that interferons are involved, I figure some JAK inhibitor might do something. Dara looks the most interesting to me, but I don’t think it’s our only hope.
 
V.R.T. said:
And that's also why I have so much hope riding on the dara trial, try as I might to not put too much hope into it
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It might be interesting to discuss what a failed trial means, not necessarily only in terms of biology but also in terms of trials. Would it mean that in the current state, without any pathological understanding of ME/CFS, that non-placebo controlled trials with positive results would be even more worthless or perhaps even useless because multiple trials have shown both subjective and certain measurements like step count improving despite no efficacy? What would that mean for drug trials in ME/CFS in general? Go straight to a blinded phase or dose-response trials? F&M's response to RTX seems to have been paying attention to fluctuations and step count. Could there be another learning? Why did PACE not show such improvements, or did it do exactly that?
 
neophyte32 said:
It s my last hope... What do we have in the near future besides daratumumab? SequencEM won't be available for at least five years, and it won't be a treatment... we have nothing.
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I don’t know your situation but there will be more causes for hope.

There is a good thread on Rational Hope of treatment: https://s4me.info/threads/rational-hope-of-treatment.42417/

As discussed on that thread, there are many more people with the requisite brains getting involved with ME/CFS research. They will come up with more ideas. The problem will be solved – and as Jo has said, it may come sooner than we think.
 
neophyte32 said:
It s my last hope... What do we have in the near future besides daratumumab? SequencEM won't be available for at least five years, and it won't be a treatment... we have nothing.
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There is a lot of research underway and I daresay a lot of more targeted stuff from new blood that will commence in the wake of efforts such as DecodeME. Any of it could blow the door open.
 
neophyte32 said:
Thank you, Professor. Regarding mitochondria, many of us have had tests done in Germany or England, and they're completely depleted... RNA sequencing shows that numerous pathways appear to be totally dysregulated. Shouldn't we be concerned about this, in your opinion?
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As far as I know all mitochondrial test used on people with ME/CFS are discredited. We have no reliable evidence of mitochondrial abnormalities. I don't know what RNA studies you are referring to but I have not seen anything consistently abnormal. 'Dysregulated' is nearly always an unjustified term for finding some differences in RNA expression in a particular cell population.

If any of this showed a consistent abnormality I would be overjoyed that we have something to go on but the combined efforts of all the intelligent people here on S4ME lead us to think that nothing ever turns out to be convincing. Researchers have got into the habit of writing papers that hype fashionable stories but all we ever see are tiny inconsistent shifts.
 
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Dude said:
Not sure if this was a paper or just a Presentation:
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Interesting technique but the summary table of results so far didn't seem to be significant for TSPO, so we will have to see what they find, and it seems to be more a marker of damage/stress to the brain or inflammation elsewhere than anything else as far as I can tell from a scan through. (Apparently it is also elevated in inflamed synovium)

Given that we do not have evidence of localised inflammation in pwME - no rubor, calor, tumor - I don't know what this may find outside the brain. And it may show nothing in the brain based on recent discussions especially around the edema paper this week that now seem to potentially suggest the opposite

I'm not convinced that mito discussion etc is relevant to the dara work and this may need a thread split
 
V.R.T. said:
I think this should be standard. If F&M had done this with dara we'd be much further on by now.
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Which part would be standard? I think this may be an oversimplification. A small placebo-controlled trial might not have told us much more (just like it didn’t in RTX) and a larger trial placebo-controlled trial is not always that easy to justify and find funding for when there is no other data. Would people have as willingly donated to the current trial had there been no open label study?
 
EndME said:
Which part would be standard? I think this may be an oversimplification. A small placebo-controlled trial might not have told us much more (just like it didn’t in RTX) and a larger trial placebo-controlled trial is not always that easy to justify and find funding for when there is no other data. Would people have as willingly donated to the current trial had there been no open label study?
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I mean that F&M should have included controls in the pilot. If none of the controls had had sustained improvements like the improvers who got the drug did, we could be a good deal more confident that the results are not placebo.
 
V.R.T. said:
I mean that F&M should have included controls in the pilot. If none of the controls had had sustained improvements like the improvers who got the drug did, we could be a good deal more confident that the results are not placebo.
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What sample sizes are we talking about? Because from RTX we know that a portion of people on placebo do report sustained improvement. Other than that it was the negative but maybe positive results at a different timepoint of the small placebo-controlled RTX study that launched the negative larger trial, so I'm a bit sceptical that just adding a few controls to the open label study would have given us much more knowledge.
 
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EndME said:
What sample sizes are we talking about? Because from RTX we know that a portion of people on placebo do report sustained improvement. Other than that it was the negative but maybe positive results at a different timepoint of the small placebo-controlled RTX study that launched the negative larger trial, so I'm a bit sceptical that just adding a few controls to the open label study would have given is much more knowledge.
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I think we could debate this til the cows come home but I disagree.
 
V.R.T. said:
I think we could debate this til the cows come home but I disagree.
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Quite possibly.

At the same time one must also consider the opposite scenario for which there is already a known history in ME/CFS: Smaller placebo-controlled trial with negative results still sometimes need a large follow-up because of Type II errors or post-hoc analyses showing something interesting.
 
EndME said:
Quite possibly.

At the same time one must also consider the opposite scenario for which there is already a known history in ME/CFS: Smaller placebo-controlled trial with negative results still sometimes need a large follow-up because of Type II errors or post-hoc analyses showing something interesting.
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The responses in the ritux pilot do not look like the dara ones - someone posted them in one of these threads the other day. They are not anything like as sustained or as large.

In phase 2 ritux failed in its primary outcomes but they went ahead because of secondary stuff iirc.

I'm not saying dara definitely works but the scenario is not identical.

If F&M had included controls, We would at least have some information on whether sustained 'responses' like in the dara pilot occur in ten pwME who recieve a placebo. And I think that would be valuble whatever it said.
 
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