Rituximab Phase III - Negative result

[Wishful]

EDIT: Maybe cyclo is our new target for hope.

If you mean cyclosporin, it didn't do anything for me when I tried it many years ago, so I wouldn't consider it a contender for a genuine ME/CFS treatment. Since none of the immunosuppressants I tried, except for the first two tries of prednisone, had any effect on my symptoms, I didn't have any faith that rituximab was going to prove an effective treatment either, so I'm not surprised at the announcement.

I think research has to focus more on the effects of cytokines on our cells, rather than on trying to reduce cytokine production. One of the recent research findings was that our cytokine levels are only slightly elevated or even 'normal', even though the patients were suffering symptoms, so the problem seems to be other than elevated cytokines.

 

[Hope123]

this confuses me, are you actually saying, you'd expect rituximab not to work for those with autoimmunity -high IgG and autoantibodies

There was a typo in my original quote which is why you found it confusing! It should say, "if you have LOW IgG...........some of this group might benefit from IVIG." Interestingly in pediatric CFS, there is a 1997 trial by Kathy Rowe showing benefit but has not been replicated. For adults, the results are more mixed but when you think about the differences in IgGs the Germans found, it makes me wonder if again the issue is one of IgG levels and subgroups.

 

[Gingergrrl]

I truly do not want to take this thread off-track but also want to reply to questions that I have been asked which relate to Rituximab.

I was also diagnosed with Hashimotos in 2003 and still have slightly raised antibodies despite treatment.

Good luck with your further treatments and great that you keep us informed of how you react to them.

Bertie, my Hashi's autoantibodies do not go down and I do not expect that they ever will. Thank you for the good wishes and I have tried to report everything re: my story in my Rituximab thread.

Now that is interesting. Thanks for sharing your history. You might have posted this before and since I'm mostly off-forum, I likely missed it: did you ever have other signs of inflammation, e.g. elevated ESR, CRP, cytokines?

Hope, I have never had elevated ESR or CRP and I have strangely never been tested for cytokines.

The more I examine the ME-ICC and CCC, the more issues I see with them.

I agree.

Additionally, a close read of the criteria shows that a patient need not have cognitive issues in either ME-ICC or CCC

I have never had cognitive issues with my illness but my lack of science background and stupid questions that I ask probably appears that I do LOL.

The work they collaborated on with the Scheibenborgen's group in Germany is interesting.

Dr. Scheibenbogen's work is fascinating to me along with Cell Trend and her IVIG/ immunoadsorption study (which I still do not know the results of unless I missed it)?

@Gingergrrl Do you think you had more benefit from IVIG vs Rituximab? Or what about MCAS treatments vs Rituximab? Just curious.

It is a great question and the MCAS meds saved my life but I was still having very frequent allergic reactions. The IVIG put my MCAS into remission 16 months ago and all reactions to food/smells are gone. The IVIG improved my blood pressure, eliminated my startle reflex and some symptoms that we wondered if were SPS, and started to improve my muscle strength. But it was not until after Ritux that I could walk around my apt without wheelchair, and walk for short distances outside. I guess each treatment built upon each other. I really do not know how to separate them b/c I still take MCAS meds (although a fraction of what I took in 2015), I am still getting IVIG, and I am still getting Ritux every 3 months.

this confuses me, are you actually saying, you'd expect rituximab not to wok with those with autoimmunity -high IgG and autoantibodies

This confuses me, too, and I would think that those with autoimmunity/auto-antibodies would be more likely to respond to Ritux (regardless if they had high IgG). I did not have high IgG starting treatment, but my IgG is a little above normal now b/c of the IVIG (but my doctor not concerned about this).

 

[jpcv]

Minute 01.23 What do you expect from Rituximab?

What language is he speaking? German?
Very good vídeo series from Dr DeMeirleir

 

[jpcv]

If you mean cyclosporin, it didn't do anything for me when I tried it many years ago, so I wouldn't consider it a contender for a genuine ME/CFS treatment. Since none of the immunosuppressants I tried, except for the first two tries of prednisone, had any effect on my symptoms, I didn't have any faith that rituximab was going to prove an effective treatment either, so I'm not surprised at the announcement.

I think research has to focus more on the effects of cytokines on our cells, rather than on trying to reduce cytokine production. One of the recent research findings was that our cytokine levels are only slightly elevated or even 'normal', even though the patients were suffering symptoms, so the problem seems to be other than elevated cytokines.

Cyclo= Cyclophosphamide

 

[Jesse2233]

Perhaps what this tells us is that a multisystem condition with large heterogeneity requires a personalized and multi-pronged treatment approach

 

[pibee]

This confuses me, too, and I would think that those with autoimmunity/auto-antibodies would be more likely to respond to Ritux (regardless if they had high IgG). I did not have high IgG starting treatment, but my IgG is a little above normal now b/c of the IVIG (but my doctor not concerned about this).

i think i understood later what he meant.. our high IgG prevent us fom catching infections so better not to beak that down... but in my own case.. i have cold every 3 weeks... i didnt have this before i had complications with unproven teatments... i never got colds.. but i dont know how high my antibodies would be then, maybe even higher, than now , which is hard to imagine. but my disease changed a lot last years.. fom never colds to constant.

 

[Gingergrrl]

i think i understood later what he meant.. our high IgG prevent us fom catching infections so better not to beak that down... but in my own case.. i have cold every 3 weeks..

Thx for explaining and I still have not had a cold, flu, or traditional illness since Jan 2013 (almost five years) in spite of doing the first three doses of Rituximab. And I really have no idea what this means except my immune system must remain in some kind of hyper-drive state?

 

[Lynne B]

Hi, everyone,

I haven't posted for a long while as I came down with acute myeloid leukemia earlier this year and have been under intensive treatment with chemotherapy and blood transfusions. In the beginning I asked if I could have Rituximab but was told this is only for those with lympocytic leukemia, not myeloid. This may have some bearing on subgroup response for Fluge and Mella's Phase III trial.

I'm now in remission but chemotheraphy continues at a lesser rate. Throughout, as part of a two year trial, I've been treated with two earlier drugs—Theoguanine and Cytarabine. I'm not suggesting either of these are potential treatment for our disease, which I've had for over 20 years. In all that time I've only had pain relief for my small fibre neuropathy and sleep disturbance. Right now I'm focused on the leukemia treatment rather than anything else but am so grateful that others continue the fight for us regardless of setbacks.

 

[Murph]

If you mean cyclosporin, it didn't do anything for me when I tried it many years ago, so I wouldn't consider it a contender for a genuine ME/CFS treatment. Since none of the immunosuppressants I tried, except for the first two tries of prednisone, had any effect on my symptoms, I didn't have any faith that rituximab was going to prove an effective treatment either, so I'm not surprised at the announcement.

I think research has to focus more on the effects of cytokines on our cells, rather than on trying to reduce cytokine production. One of the recent research findings was that our cytokine levels are only slightly elevated or even 'normal', even though the patients were suffering symptoms, so the problem seems to be other than elevated cytokines.

whoops sorry no, cyclophosphamide. The same Norwegian researchers have a big trial on that ongoing. It actually got unblinded before the Rituximab trial so the fact they haven't poured cold water all over it suggests maybe it is going to report positive results??

cyclo kills b cells and t cells, and t cells have recently been implicated in the disease.

 

[Murph]

In the context of today, a thought on whether forums like this can help people distinguish effective treatments.

Maybe they can. As it turned out, @Hip's non-blinded, non-ethics approved, non-funded roundup of people who claimed to have tried rituximab may have given us the best heads-up into the prospects of Phase III. (Hip found far more non-responders than responders.) Hip had nothing to sell, no prizes or promotions to win, and only sought the truth.

It lends some credence to the Julie Rehmeyer school of exploiting the non-structured information you can find online, rather than only waiting for the formal and highly structured information that emanates from randomised controlled trials. RCTs are great quality evidence but awfully rare. You can do science starting with non-structured information. You just have to be careful.

I've been pondering @Jesse2233 's discovery of a large group of people with an improvement from mhbot. On the one hand, it's not formal science. On the other hand, it is evidence of a kind. Today's result makes me more inclined toward carefully placing belief in patient self-reports, (if they're numerous and dispersed enough and you can find reason to believe they're not affected by a common error such as a charismatic clinician or LP style brainwashing process .)

 

[helperofearth123]

 

[Aubry]

Another 5? years lost... They might as well give us euthanasia papers now ...

 

[msf]

Two things:

One, I am very disappointed for those with severe ME. The silver lining for me is this: either cyclo works, and everyone is happy, or we know this is a blind alley, and research efforts are concentrated on the areas being studied by the American and Belgian researchers, which I feel is based on a better understanding of the disease.

Two (much less important, but something I feel I need to say anyway): the way those who put their faith in Rituximab criticised those researchers and ME patients with alternative, non-autoimmune theories for the disease now looks somewhat premature, and I hope in future people treat alternative scientific approaches with more respect. Some may think that I am just referring to KDM here, but I am not: I am referring to all those who did biomedical research in ME before Fluge and Mella came along (by the way, I do not include either of them amongst those who ignored the achievements of other researchers).

 

[pibee]

I've been pondering @Jesse2233 's discovery of a large group of peo

In the context of today, a thought on whether forums like this can help people distinguish effective treatments.

Maybe they can. As it turned out, @Hip's non-blinded, non-ethics approved, non-funded roundup of people who claimed to have tried rituximab may have given us the best heads-up into the prospects of Phase III. (Hip found far more non-responders than responders.) Hip had nothing to sell, no prizes or promotions to win, and only sought the truth.

It lends some credence to the Julie Rehmeyer school of exploiting the non-structured information you can find online, rather than only waiting for the formal and highly structured information that emanates from randomised controlled trials. RCTs are great quality evidence but awfully rare. You can do science starting with non-structured information. You just have to be careful.

I've been pondering @Jesse2233 's discovery of a large group of people with an improvement from mhbot. On the one hand, it's not formal science. On the other hand, it is evidence of a kind. Today's result makes me more inclined toward carefully placing belief in patient self-reports, (if they're numerous and dispersed enough and you can find reason to believe they're not affected by a common error such as a charismatic clinician or LP style brainwashing process .)

I relied on forum/Facebook groups methods for 3 years, in a lack of doctors and finances, got me nowhere. Even after seeing 5000 reports on success w autoimmune illnesses on Coimbra protocol with high dose vitamin D, it managed to mess me up.
And I read a lot before and couldnt find real negative experience. 3 people warned me Lyme responds badly to it, but that was 3 vs 5000 success stories
And I was 4th
And now I know some more, most have likely infecions

P.S. I did have also amazing improvements w 50% of symptoms but worsened most of my cognitive symptoms except apraxia(psychomotor)which imoved extemel, but all in all end result was worsening ....

now I like self reports on groups but only if it really cant damage

mHBOT is I believe worth trying but even that you cant exclude possible negative effects. I spent lot of times on ozone groups too, I am not too eager to play with that either


Just saying we should be very careful with online reports, I learned the hard way.

I never ever seen so high level of reported success as with Coimra protocol online. Documentaies too.

It has 100+ doctors doing it, so many patients stories, so many Facebook groups..worldwide. They said it cant hurt

 

[Hip]

It's of interest that in both Fluge and Mella's doubled-blinded phase II trial (30 patients, 67% response rate) and their open label phase II trial (29 patients, 64% response rate), the CDC Fukuda definition was used to recruit patients.

Whereas in the phase III trial, they used the stricter Canadian consensus criteria.

EDIT: actually the above statment is in error, as was pointed out to me in this later post. In fact in all the trials, patients mostly satisfied the CDC Fukuda and the CCC.


This returns us to the idea that ME and CFS may be different diseases, and that rituximab works for CFS but not ME.

Although I don't myself tend to subscribe to this idea that ME and CFS are different.

 

[pamojja]

I relied on forum/Facebook groups methods for 3 years, in a lack of doctors and finances, got me nowhere. Even after seeing 5000 reports on success w autoimmune illnesses on Coimbra protocol with high dose vitamin D, it managed to mess me up.
...
It has 100+ doctors doing it, so many patients stories, so many Facebook groups..worldwide. They said it cant hurt.

If one reads the actual Coimbra protocol against MS, it's very clear that one precedes on very thin ice without supervision of a knowledgeable doc and regular lab testing. It is very clearly said without doc it can hurt.

And that is the assessment of someone very proficient in mega-dose vitamin/mineral/amino acid therapy ala Linus Pauling for 9 years with great results against PAD, and a number of minor conditions. Not ME/CFS though.

However, with my experience with PAD, a form of CVD every second of us will die from, and the complete inability of medical science to make much progress with all the money thrown at it for half a century - makes me totally disbelieve that the same kind of science thrown at ME/CFS would be any more successful.

Think with such multi-factorial diseases, like cancer, CVD or ME/CFS, it's very unlikely to be cured by one magic pill, but by a multi-thronged approach only. At least that's my experience with one such merciless disease, which gives me hope. Most likely here also much more than a single patentable compound is needed.

 

[pibee]

It's of interest that in both Fluge and Mella's doubled-blinded phase II trial (30 patients, 67% response rate) and their open label phase II trial (29 patients, 64% response rate), the CDC Fukuda definition was used to recruit patients.

Whereas in the phase III trial, they used the stricter Canadian consensus criteria.


This returns us to the idea that ME and CFS may be different diseases, and that rituximab works for CFS but not ME.

Although I don't myself tend to subscribe to this idea that ME and CFS are different.

Now, why did they do that

If one reads the actual cprotocol against MS, it's very clear that one precedes on very thin ice without supervision of a knowledgeable doc and regular lab testing. It is very clearly said without doc it can hurt.

And that is the assessment of someone very proficient in mega-dose vitamin/mineral/amino acid therapy ala Linus Pauling for 9 years with great results against PAD, and a number of minor conditions. Not ME/CFS though.

I had Coimbra trained, 'knowledgeable' doctor...and regular labs... but they dont know much since no studies..I spoke to Coimbra personally several times, he is your classical know-it-all quack and never gave answer to any of my science related questions ...
all other people i know that had poblems with potocol, most have MS, were all under doctor's supevision.

my point was, online they onl report good outcomes...not sure why you think its thin ice if pactically no negative reports and thousands positive..cant look better
and othe point is, that dose was too high, i still believe it can somehow work but without studies you basically dont know what it does and why some impove and othes get worse....

i had initially very good response.. so it was a bite. dont want to derail this thread, if you have any questions send me PM

 

[maybe some day]

sad..but not surprising..i'm done reading about me/cfs,it's pointless , every study research is in vane ,simply because it s not the same disease for everyone..simillar symptoms ,but different disease needing differrent people..i need to free myself from this, this road will never lead to anywhere

I agree..if they figure it out in my life time so be it. But I dont have my hopes up thats going to happen. Besides if it did show promise, its not like insurance companies will gladly hand it out. Thats a whole different battle.

 

[Snoozermcsleepsalot]