B-Lymphocyte Depletion in Patients With ME/cfs: A Randomized, Double-Blind, Placebo-Controlled Trial (2019) Fluge et al

[Adam pwme]

Does the 18.9% serious adverse events in the placebo group suggest that adverse events in PACE were not properly recorded?

 

[ME/CFS Skeptic]

Does the 18.9% serious adverse events in the placebo group suggest that adverse events in PACE were not properly recorded?

Good question. In the PACE-trial only 8% of participants in the GET group and only 4% in the CBT group had serious adverse events. Can't access the Fluge et al. paper yet, but it will be interesting to compare this outcome with what was reported in the PACE-trial.

 

[Peter]

So good to Rituxme finally published. Nice to see such a well conducted study, and what a contrast to Wyller, the people who talks about LP and all that pseudo.

The result is as we all have known for a long time negative, but this is still what it is all about. A hypothesis that can be tested and the method in place. That is exactly what patients want, but the BPS-brigade misses out on this obvious point when talking about patients steering science in a direction. That is just utter rubbish. Patients wants science and that’s all.

Thanks to the team at Haukeland for gaining knowledge and plugging on.

 

[Jonathan Edwards]

Does the 18.9% serious adverse events in the placebo group suggest that adverse events in PACE were not properly recorded?

A reasonable questipn but I think defonition of seripus adverse event is alwaysgoing to vary from trial to trial. I thinl this result may indicate the vigilant approach in Norway. As to PACE I am not sure anything changes!

 

[rvallee]

I agree, kudos to drs Fluge and Mella.

Now we know and now we can move on.

But. I was told by eminent professors that we threw tantrums about research when we don't like the results and should be expected to go on a rampage any minute now. Lock the gates. Hide the kids and pets, you never know what our bloodthirsty hordes will do!

How. How could that be? Surely they did not... *gasp*... lie?! That would be very, very unethical and unbecoming.

Reality shattered

 

[rvallee]

I'm curious about the 18.9% in the placebo group that had "serious adverse events." Would this be the so-called "nocebo" effect, and can that actually produce serious adverse events? Or might these events have been part of the disease process itself and unrelated to the study?

Normal fluctuations of the disease definitely could explain that. Incredibly frustrating to have to take account of this much unpredictability. And it works both ways. No doubt some of the "improvements" in psychosocial studies are explained by some of this randomness, which likely disappeared and fluctuated wildly between the time the self-reported questionnaire was completed and when it was analyzed.

 

[rvallee]

I agree that we should congratulate F and M for not only doing an excellent study but for providing a genuine gold standard for me trials. The futility of unblinded studies becomes transparent.

Absolutely.

Clearly a controversial opinion, sadly, but real objective science > subjective, ideologically-motivated outcome-seeking. Any day of the week. Hell, every planck time unit of the whole of existence.

Guess we riot now? According to Sharpe and Wessely this should be expected any minute.

Any minute...

 

[rvallee]

Sheesh, some people forgot to read The Memo.

I mean, how are we going to keep reinforcing the BPS narrative about us being rabid oppressive anti-science activists if we are going to recognise and praise high quality science like this, and fully accept its results, even if negative for us?

Speak for yourself. I'm so mad with rage I want to destroy erlenmeyer flasks and do controlled chemical burns on periodic tables. That's how anti-science militants rage, with spit by the mole-full while we curse Newton and whack away at Darwin pinatas.

Oh, wait, April fool's was yesterday. Nevermind.

 

[rvallee]

Does the 18.9% serious adverse events in the placebo group suggest that adverse events in PACE were not properly recorded?

I most definitely expect that they were not.

Anyone doubt that?

After all it's in the premise that it is harmless. Can't continue arguing that it's harmless (despite no evidence of that) when you report harm. Bit of a contradiction.

 

[Marky]

I most definitely expect that they were not.

Anyone doubt that?

After all it's in the premise that it is harmless. Can't continue arguing that it's harmless (despite no evidence of that) when you report harm. Bit of a contradiction.

Might also have been more mild cases in PACE considering the criteria they use? Also didn`t a lot of patients drop out of PACE for undisclosed reasons? I dont remember exactly

 

[hinterland]

The 35% response in the placebo group shows how poorly conceived the BPS studies, some of which don't even have good placebo controls, have been.

I agree, but also worth noting that the placebo wasn’t a dummy pill in this study: it was 500ml IV saline, this could conceivably provide some temporary symptom relief in volume depleted patients, a condition that has been shown to occur frequently in pwME. I wonder if, on observing this, some patients suspected they were on active treatment and this biased their self-report?

 

[Marky]

I agree, but also worth noting that the placebo wasn’t a dummy pill in this study: it was 500ml IV saline, this could conceivably provide some temporary symptom relief in volume depleted patients, a condition that has been shown to occur frequently in pwME. I wonder if, on observing this, some patients suspected they were on active treatment and this biased their self-report?

I haven`t gone through the individual data yet, but that effect should disappear anyway in the long term follow up?

 

[Jonathan Edwards]

I agree, but also worth noting that the placebo wasn’t a dummy pill in this study: it was 500ml IV saline, this could conceivably provide some temporary symptom relief in volume depleted patients,

It ought to have the same effect as taking four hours to drink a bowl of rather salty soup, unlikely to last more than afurther hour.
I doubt it could be relevant.

 

[hinterland]

That makes sense. I'd assume that a similar percentage in the rituximab group (~19%) would have adverse effects for the same reason, leaving 7% (or more, due to overlap) to other causes.

Does anyone know if patients in the placebo group got active premedication before their main course of ‘Rituximab’, or were all their meds fakes? Isn’t Ritux usually served following a starter of glucocorticoids, and possibly some other stuff? These might be a possible cause of adverse reaction, in some cases.

 

[hinterland]

Does the 18.9% serious adverse events in the placebo group suggest that adverse events in PACE were not properly recorded?

I suspect that is the case, but also patients in Fluge et al were likely more severely affected with limited mobility.

 

[Kalliope]

Article in Medscape by Miriam Tucker. Log-in is required.
Rituximab Fails to Improve Symptoms in ME/CFS

 

[Milo]

Does anyone know if patients in the placebo group got active premedication before their main course of ‘Rituximab’, or were all their meds fakes? Isn’t Ritux usually served following a starter of glucocorticoids, and possibly some other stuff? These might be a possible cause of adverse reaction, in some cases.

Typically placebo controlled are getting the same premedication as if you were receiving the drug. Nurses do not know what is in the Iv bag when it comes time to infusion.

 

[FMMM1]

It has always seemed to me likely that a small proportion of people diagnosd with ME/CFS have misdiagnosed autoimmune diseases. There will be a few with ANA related disease. However, this trial makes it less likely that any significant prportion do.

The trial does not exclude the possibility of some autoimmune cases that are not rituximab responsive. Fatigue with ANA related autoimmunity often does not respond. But of course that means there is no point in looking for 'hidden responders'. Looking at the people who got beter in this study is I think a waste of time.

Based on a very brief glance, this article seems to suggest that Dr Naith believes autoimmune antibodies play a role in ME (http://simmaronresearch.com/2019/04/nath-chronic-fatigue-syndrome-east-african-disease-model/). The used "a kind of protein chip technology that allowed them to screen for thousands of antibodies at once" i.e. to try to identify the sequence the auto-antibodies are targeting. @Jonathan Edwards what do you make of this technology; are you aware of a disease where it has helped identify the auto-antibodies/there target?

I agree with your statement above i.e. that the results of the rituximab trial mean that it is unlikely that a significant proportion of people with ME have an autoimmune disease.

 

[Milo]

I agree with your statement above i.e. that the results of the rituximab trial mean that it is unlikely that a significant proportion of people with ME have an autoimmune disease

Rituximab is not a treatment of “all” autoimmune diseases...

 

[Snow Leopard]

I'm curious about the 18.9% in the placebo group that had "serious adverse events." Would this be the so-called "nocebo" effect, and can that actually produce serious adverse events? Or might these events have been part of the disease process itself and unrelated to the study?

Mostly unrelated to the study. This is one of the key reasons why control groups are used...

Does the 18.9% serious adverse events in the placebo group suggest that adverse events in PACE were not properly recorded?

Politely, I'd say the difference in reported adverse effects is certainly in part due to methodological differences.