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

Males responded more strongly to placebo treatment​

A systematic review of sex differences in the placebo and the nocebo effect​


A systematic review of sex differences in the placebo and the nocebo effect - PMC

The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect. A literature search was conducted in multiple electronic databases. Studies were included if the study compared a group or condition ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
 
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Also this is good news….

Probably don’t have to live in a plastic bubble for the rest of your life.

Protective antibodies (Diphtheria, Tetanus, SARS-CoV2) were analysed at baseline and after 12 months follow-up. All patients had SARS-CoV-2 antibodies in line with either a previous infection or vaccination. All patients had protective or probably protective levels of antibodies to SARS-CoV-2, Diphtheria and Tetanus, both at baseline and after 12 months.
 
What’s interesting is some of the graphs don’t look that “noisy” or “random”. Like it doesn’t seem far fetched to me to make out the two groups “responders” and “non-responders” Fluge and Mella propose.

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Yann04 said:
What’s interesting is some of the graphs don’t look that “noisy” or “random”. Like it doesn’t seem far fetched to me to make out the two groups “responders” and “non-responders” Fluge and Mella propose.
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Given that nobody knows whether there even is a signal or noise or what is what I don't think you can see anything in such graphs. If they'd all just gotten a placebo the differences between "responders" and "non-responders" might just look similar. I wouldn't be suprised if you could take some snapshot of people in the Rituximab trial that weren't given the drug and find a similar image. Defining someone to be a "responder" by saying they got better and then retrospectively suggesting a differentiation between "responder" and "non-responder" seems entirely circular.
 
Jaybee00 said:
Why does the 4 Dara line extend further in time than the 4 + 3 line? Did the 4 + 3 start later?
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Yes, four patients were added later:
After observation of these first six patients, no serious adverse events (SAE) were recorded. Two patients experienced sustained and marked clinical improvement, and one a more transient, moderate improvement. To further explore dose–response relationships, an amendment was filed and four additional patients were included from June 2023 to December 2023. These four received the initial four injections 2 weeks apart and, provided there were any clinical signs of benefit 6 weeks after the fourth injection, a further three additional injections at weeks 14, 22 and 30.

All 10 patients received the planned number of subcutaneous Darzalex injections, in total 52. The first six patients completed follow-up from week −12 to week 40, and added follow-up visits according to protocol amendment at weeks 66 and 92. The last four patients completed follow-up from week −12 to week 48, and have yet to complete extended follow-up.
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Jaybee00 said:

Males responded more strongly to placebo treatment​

A systematic review of sex differences in the placebo and the nocebo effect​


A systematic review of sex differences in the placebo and the nocebo effect - PMC

The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect. A literature search was conducted in multiple electronic databases. Studies were included if the study compared a group or condition ...
pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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I don't see how that would of any relevance to ME/CFS, because you have so many other placebo-like effects in ME/CFS (Hawthorne effect, natural fluctuations etc) that could easily dominate the observations of the above studies but for which there is no evidence to suggest that they are somehow sex dominated.

I think the only interesting scenario is where there would say be a set of 2 illnesses falling under the ME/CFS label with different sex proportions and a different response to Daratumab. But in that case you're anyways not going to get any answers from a small open-label trial and any other patterns would hopefully become visible in the larger follow-up (and if such patterns still remain hidden in the larger follow-up then inclucing additional males in your open-label obviously also wouldn't make any difference to begin with). Paradoxically I'm wandering whether that possibly means, retrospectivelly because they got a positive result, that it might have actually been advantageous to not include any males in the open-label trial (if one was to ignore effects of a mediciation that ends up being ineffective for both illness groups, which is a very bold assumption because these drugs are very heavy so that's a massive caviat, especially because the authors have seen things before that turned out to not be related to drug efficacy ) precisely because the authors believed to have found a signal that they are now examining further (if males are more likely to suffer from an illness not responsive to the drug this might have deliuted effects such that there would be no follow-up and if there is a follow-up effects or non-effects of different illness clusters can anyways be examined which would be beneficial to both groups irrespective to which group they belong to).
 
EndME said:
You're only going to get any answers from the following study.
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The problem is that there are risks in waiting for the perfect flawless study. If you are willing to the 5-6 years or so for the phase 2 Dara results to be published you risk having your NK cells fry out (lower than ~150) at which point the phase 2 trial won’t be relevant to you. At that point you are probably going to have to wait another 10 years or so for a trial of something like Teclistamab or CAR T cell therapy (or cyclo), all of which are significantly more dangerous than Daratumumab.
 
Jaybee00 said:
The problem is that there are risks in waiting for the perfect flawless study. If you are willing to the 5-6 years or so for the phase 2 Dara results to be published you risk having your NK cells fry out (lower than ~150) at which point the phase 2 trial won’t be relevant to you. At that point you are probably going to have to wait another 10 years or so for a trial of something like Teclistamab or CAR T cell therapy (or cyclo), all of which are significantly more dangerous than Daratumumab.
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Although it says 2030 completion on the clinical trial site are we really sure it's going to take that long? Seems ages for a relatively small phase 2.
 
EndME said:
Given that nobody knows whether there even is a signal or noise or what is what I don't think you can see anything in such graphs. If they'd all just gotten a placebo the differences between "responders" and "non-responders" might just look similar. I wouldn't be suprised if you could take some snapshot of people in the Rituximab trial that weren't given the drug and find a similar image. Defining someone to be a "responder" by saying they got better and then retrospectively suggesting a differentiation between "responder" and "non-responder" seems entirely circular.
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Agreed. I’m not saying the logic checks out. I’m saying the graph doesn’t look especially noisy it looks almost bimodal. So I kind of understand where the idea of dividing into those two groups came from.

But I think obviously no one is claiming anyone had a genuine response to the drug for sure. Just that the graph doesn’t match the sort of “in betweeners” you seem to see in some placebo effects. Though that could of course all be fairly likely randomness effects in themselves, cherry picking, or just the fact the sample is miniscule.
 
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V.R.T. said:
Although it says 2030 completion on the clinical trial site are we really sure it's going to take that long? Seems ages for a relatively small phase 2.
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Probably yes. The only recent drugs where it seems like they are able to complete large clinical trials quickly are the GLP1 trials, where there is huge money resting on outcomes.
 
OrganicChilli said:
Does that really happen? Because it would mean dara is not an option for anyone who got sick pre-covid.
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No. If NK cells "frying out" was a property of ME/CFS duration we'd know by now. This is all just pure conjecture and of course it doesnt even match the data of the pilot study, in fact it is the opposite of what the data of the pilot study says.
 
The planned followup for phase 2 is 72 weeks. Recruitment is uprn until Dec’26, but participants will never be a bottle neck (they could probably do 10x).

My guess is that the results will be out in 2027 if they get the funding sorted.
 
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