Yes, Dara is used for b-cell depletion, but it has many other effects, some known and some unknown. Cell depletion per se might be irrelevant for ME/CFS.
I understand. Seeing the correlation between improvement and NK cells, a sustained drop in IgG, as well as early data on immunoadsorption, I became excited about the hypotheses of Fluge/Mella and Scheinbogen.
I think the «responders» had a similar step count with Ritux, when you correct for the different types of sensors. See e.g. this
comment.
From what I saw, F/M were not very clear about the difference in step counts between those who improved and those who did not in the previous studies. Here, it seems they tried to rely on more objective data.
There are also some
anecdotes about long-lasting but eventually unsustainable increases in activity following Lightning Process courses.
I don’t know for how long improvements were reported, but I’m not aware of any that lasted 12–24 months. Everything about LP and Born Free is very suspicious (reports of improvement that were probably not genuine / people angry about having been misled).
And of course the spontaneous recoveries in the NIH study (the effort preference one).
Patients with recent-onset disease, mild enough to undergo a 1-day CPET (people with more severe PEM would tend not to be included in the study). There is a higher chance of false diagnoses and of selecting people who mainly want to take a test to find out what they have (indeed, 20% left the study after receiving alternative diagnoses), and the paper does not describe with any score or metric how patients were at baseline and how they ended the study.
On the other hand, Fluge and Mella selected patients with moderate to severe disease, most of them ill for more than a decade, and people willing to use a potent immunosuppressant. A different selection profile. I know, it was the same with Ritux.
It seems to me that the odds would be against spontaneous recovery in 4/17, as well as in 6/10. Of course I'm just hoping that the synchronized improvement after 6–8 weeks (or 2–4 weeks after the last dose of daratumumab, as in the five cases in the extension study), together with the correlation with NK cells and IgG, might mean something.
But I understand. These are small studies of a disease without a biomarker, and without a control group. Any analysis in this direction is ultimately just wishful thinking — or, at best, a reasonable starting point.
Yes, it might be a bit too soon for those discussions because there are still so many unknowns.
If Fluge and Mella are thinking autoimmune, it’s hard to imagine a long-lasting autoimmune disease that doesn’t require a maintenance treatment regimen (as they tried in phase II Rituximab studies). But you’re right, they first need to prove autoimmunity or the efficacy of an inducing drug before considering how to treat those ‘relapses’ (even though they are already doing so in one patient by repeating Dara).
