Rituximab Phase III - Negative result

[jaybee00]

ughhh

What was the endpoint in this study? Were they looking at response 6 months post first infusion? 1 year?


Maybe they had an abnormally large number of responders in the placebo group?.........

 

[Starlight]

This is disappointing news,hugely so,but it is honest science ,science at its best.there was no attempt to spin anything and it can be looked at.,examined for what is of value in it and we know it is the truth. I am sad but I can take it purely because of this..I'm not even sure the impact has really hit me because I had so much hope for this,I had felt sure it would be the answer for some of us,I hope Fluge and Mella will stay with us. It is refreshing that it is not lies we are reading and hearing about today as we have had to put up with from other quarters for so many years and which are still being g foisted on us. I feel devastated when I think of how different today would be if these results had gone our way. But knowing this is truth helps.

 

[jaybee00]

To answer my own question....

The difference in course of Fatigue score during 24 months follow-up, between the rituximab and placebo groups, will constitute the primary endpoint

 

[Dechi]

I am so disappointed. I feel really down now. @lnester7 my puppy died too ! :-(

 

[KristenSF]

I expected at least to see the 30% of autoimmune as positive results. This is very bizarre disappointing and unexpected, I feel as if my Puppy died.

So does a negative result mean none of the patients improved? I'm so confused!

 

[Hajnalka]

Statement from Invest in ME (mentions @Jonathan Edwards):
http://www.investinme.org/IIMER-Newslet-1711-03.shtml

 

[Gingergrrl]

@Marky90 or @deleder2k Is there a link to the study results and I am missing it? Or was it just a press announcement and the results are to follow later?

I have no idea if this is helpful to anyone, but I have responded to Rituximab and I am certain that there are others in the world who must be in the same "sub-group" as me. I know I cannot have a disease that no one else on the planet has and am not that unique.

My doctor feels that I have "Autoimmune POTS" (and he believes that some day this term will be understood by medicine even though it is not at present). He also feels I have something similar to LEMS b/c of the calcium autoantibody that weakened my muscle strength and breathing, in addition to have POTS. Doctors have told me that people with just POTS do not have the level of muscle and breathing issues that I had.

I am absolutely not even close to being cured or near pre-illness levels but my MCAS/allergic reactions remain in remission, my muscle strength is now normal, my breathing is better, POTS better, walking better, etc. I wish I knew why the IVIG and Ritux helped me but am certain it can help others with similar auto-antibody or symptom profiles.

I have no idea what happens when I stop IVIG and Rituximab, and I may be back at square one. The best I hope for is remission, and I do not believe there is a cure.

 

[Nic S.]

It's just awful news, just so drenching, so demoralizing.
But now more and more I'm starting to wonder maybe folks don't all have the same illness at all.

Yeah, ditto. I'm inclined to think we've got a situation somewhat similar to a lot of cancers. Even when you have what the general public think of as a single illness (e.g. "breast cancer" or "brain tumour"), when you start looking deeper in order to figure out a treatment more complicated than the brute force "surgically remove the problem and encourage the body to police its own cells" (which of course you can't do with ME!), suddenly you find that there are actually multiple mechanisms, many of which are starting from completely different places - and the only point of similarity is the way that they all end up having the same end effect on the body.

So yeah. Subgroups. We really need to start sorting that out.

And that might well explain a few of the other research fade-outs we've had over the years, when a researcher does a small-scale limited study, possibly accidentally ending up with a cluster of the same subgroup, and then when it's repeated on a larger scale or in a different location, hey presto, the results disappear!

 

[Aubry]

KDM told me Rituximab wouldn't work longterm. But I wonder what will ever

 

[pibee]

Was I the only one who questioned her own sanity for at least a second when I read the results are negative..
identity..crisis . is it even autoimmune...is it one disease.. racing thoughts...

 

[Gingergrrl]

Sorry I was typing while @Joh posted the link and have now read it. It sounds like they are saying the results are negative for ME/CFS but they did not give specifics re: percentages or the group that were responders. Wasn't there a group from the study (1/3) who were responders or am I totally mis-remembering this?

 

[Gingergrrl]

is it even autoimmune...is it one disease.. racing thoughts...

I believe it is autoimmune for a sub-group and that it is not one disease. But I of course could be 100% wrong and have nothing solid to back up my opinion.

 

[thijs]

Odd how this Fluge and Mella phase III trial failed to find any positive effect, yet Kolibri Medical clinic in Norway reported that rituximab treatment cures ⅓ of ME/CFS patients, makes an improvement in another ⅓ of patients, and has no effect in the final ⅓ of patients. Ref: 1

This Kolibri's results are consistent with the phase II study, which found 60% of patients made a major improvement.

Phase 2&3 results don't have to contradict each other.

The placebo response in the new study could have been high.

ME/CFS placebo responses were low in the past, but there wasn't much to be optimistic about. Patients had high expectations for this treatment.

 

[Gingergrrl]

ME/CFS placebo responses were low in the past, but there wasn't much to be optimistic about. Patients had high expectations for this treatment.

Did they measure anything that was purely objective and could not be placebo? In my case we measure different blood markers, how long I can stand and walk without wheelchair, spirometry/breathing tests, HR & BP and autonomic measurements, muscle strength, etc. I don't have fatigue (which is hard to "measure" IMO anyway) so I was wondering how they determined if someone was a responder? Was it purely by questionnaires or something objective and measurable?

 

[pibee]

I believe it is autoimmune for a sub-group and that it is not one disease. But I of course could be 100% wrong and have nothing solid to back up my opinion.

I think rituximab works for only 40% of RA, which is universally considered AI, as much as I know
Also for PPMS, progressive MS, only ocrezulimab works fo ˇ20%.
I always wondered why ME rarely shows relapsing remitting subset like RRMS, at least i don't see it much, I know papers say it is RR form but seems like most of us crash and stay so...
paralel w PPMS, SPMS

But by questioning my sanity I meant simply because there is no biomarker, model of autoimmunity is closest we've got so far and now again not confirmed.

Hope at least p was close to significance, p < 0.10, but they'd mention that

 

[Martin aka paused||M.E.]

Did they measure anything that was purely objective and could not be placebo? In my case we measure different blood markers, how long I can stand and walk without wheelchair, spirometry/breathing tests, HR & BP and autonomic measurements, muscle strength, etc.

Technical speaking that could be due to placebo effect too...

 

[thijs]

Did they measure anything that was purely objective and could not be placebo? In my case we measure different blood markers, how long I can stand and walk without wheelchair, spirometry/breathing tests, HR & BP and autonomic measurements, muscle strength, etc. I don't have fatigue (which is hard to "measure" IMO anyway) so I was wondering how they determined if someone was a responder? Was it purely by questionnaires or something objective and measurable?

There were objective measures, but it's unclear if they were negative as well, or if they were referring to only the questionaires. https://clinicaltrials.gov/ct2/show/NCT02229942

But i'm not sure if it's possible to exclude placebo effects completely. Like this post states, objective measures sometimes still show some improvement. There is also a natural course.

 

[Scarecrow]

Did they measure anything that was purely objective and could not be placebo?

I don't know about purely objective but they did use Sensewear Armbands but only for a limited period of time.
https://clinicaltrials.gov/ct2/show/NCT022299

Physical activity (Sensewear armband) [ Time Frame: Analyzed at baseline and at interval 17-21 months ]
The patients' physical activity level, in a home setting for 7 consecutive days, is recorded using Sensewear armbands, with registration at baseline and repeated in the time interval 17-21 months follow-up. Changes from baseline to analysis during the time interval 17-21 months, for mean number of steps per 24h, maximum number of steps per 24h, mean duration per 24h with activity level at least 3.5 METs, max duration per 24h with activity level at least 3.5 METs, are recorded. The difference between rituximab and placebo groups will constitute secondary endpoints.

Also the conducted further studies in parallel to the trial.

Three substudies will be performed:

Endothelial function: assessment of Flow-Mediated Dilation and skin microcirculation at baseline and repeated during the time interval 17-21 months.

Cardiopulmonary exercise test for two following days: assessment at baseline and repeated during the time interval 17-21 months.

Gastrointestinal function: assessment at baseline and repeated during the time interval 17-21 months.

deleder2k said that they have observed Flow-Mediated Dilation but I'm not sure if he means previously or during this current trial.

 

[Simon]

Yes. Failures teach science almost as much as successes.

Almost

I'd rather a real success to a real failure. But I'd rather have a real failure than a gamed success - yes, I'm talking about the PACE trial, of course, but about much biomedical research too.

Progress in science is like slowly building a house, brick by brick. If some of the brick crumble then the house never rises. I honestly think that's a big reason progress has been so limited over the years, despite thousands of studies. Yes, apalling lack of funding is a huge problem, but brick-quality has never seemed to be taken very seriously either. This new brick looks solid.

I think my metaphor collapsed a while ago so I'll leave it there.

 

[Nico]

There is a German doc in Munich who is treating a CFS-patient that got much worse under Rituximab. He is completely disabled due to only one injection. I don't know if he has ever recovered... But I think he did not!

That was a German soccer player. There was an interview with them, and Miktovits. When they talked she said that with the dosage they gave him that it was no wonder that he became more ill. It's in here somewhere. The intro starts out in German, but the rest is in English.