IVIG Treatment

[Rooney]

Jonathan,
Thank you so much for jumping in. I have missed your thoughts.

I am moderate in severity. I was approved for IVIG last spring due to supporting poor labs showing low globulins, high lymphs, ect. No autoimmunity. After several months of Gamunex, each infusion would give me a few weeks of encephalitis. The only benefit was improved labs and skin healing. I never discussed steroid pre-med with my Dr. and he never suggested it. It's a pickle. Thoughts dare I ask?

 

[Gingergrrl]

Sorry GG, I respect your approach and your need to find a solution but your case is no proof of anything. That is the raw truth. Science does not make use of uncontrolled observations like that, except to set up proper studies.

By "proof" I meant that my case shows that IVIG and Rituximab have been effective treatments for me and I don't want others who could be potential responders to one or both treatments to be lost forever b/c of research studies with subjects who may be entirely different than them. Four doctors who treat me and ran extensive labs and other tests (ME/CFS doc, MCAS doc, Endo, and Cardio) all feel that I am on the right path and that these treatments have been effective for me.

But the true test is my improvement in symptoms both subjective and objective (number of steps walked without wheelchair, muscle strength, autoantibody testing, spirometry testing, complete remission of allergic reactions, etc). If this is placebo, or whatever you want to call it, I will take it gladly (even though none of my doctors believe that and would consider the idea absurd).

If it brings you joy to publicly state that the "raw truth" is that I am not proof of anything, that is fine. I can deal with it because it does not change the incredible outcome that I have had thus far. I should note that you are not my doctor and have never examined or run labs on me and the ones who have (all four respected doctors) believe my improvements are directly related to these treatments (IVIG for 1.5 years and thus far, three infusions of Rituximab).

 

[RYO]

I tried SC Gammagard during summer of 2016. It definitely didn't help. I've had severe relapse with prominent brain fog. It is unclear if symptoms related to Gammagard.

Those of us with moderate to severe symptoms are desperate. Results of rituximab trial are disappointing but I am also relieved. I was always apprehensive about potential side effects.

Unfortunately, we will all be relegated to shotgun approach and quack treatments unless there is progress in quality research.

When they asked Dr Nath at the NIH to become the PI for intramural study, he started by looking the existing research. He came to the same conclusion as many scientists, that existing studies are limited in size and quality.

Realistically, I would be ecstatic if within 5 years we finally develop a basic understanding of the pathophysiology of ME/CFS (biomarker, differentiate subsets, tissue level findings etc)

They have known about the intricacies of sickle cells disease over 50 years. Sickle cell patients often endure a lifetime of severe pain with most succumbing in their 40s. It's only recently that there is hope with stem cell transplants and possible gene based therapy.

We need more disease advocacy and funding. We Need More Disease Advocacy and Funding. WE NEED MORE DISEASE ADVOCACY AND FUNDING!!!

We need someone with considerable resources to be personally affected by this disease.

 

[Ema]

It relies on the notion that patients in studies are carefully selected identical widgets, with identical genes, hormone and nutrient status, toxic and infectious exposures, health histories, and comorbidities. Unfortunately, this is impossible, even with twin studies. People are not identical widgets and studies can't be repeated exactly.

THIS ^^^.

“Although evidence based medicine has reshaped medicine, nursing, and allied health professions into knowledge driven, scientific (sometimes pseudoscientific) professions, it fails to tackle the multifactorial reality of what actually happens to patients—the “art” of helping humans. The science of evidence based medicine is largely reliant on consistent, reproducible conditions, but humans are not consistent, reproducible creatures, be they patients or practitioners.”

– Catherine J Welch

Welch CJ (2017). Evidence based medicine misses the “art” of helping humans. BMJ 2017: 358:j3426.

 

[RYO]

@Ema
We need both. They are not mutually exclusive. I would like good science delivered by caring practitioners.

 

[Jonathan Edwards]

Jonathan,
Thank you so much for jumping in. I have missed your thoughts.

I am moderate in severity. I was approved for IVIG last spring due to supporting poor labs showing low globulins, high lymphs, ect. No autoimmunity. After several months of Gamunex, each infusion would give me a few weeks of encephalitis. The only benefit was improved labs and skin healing. I never discussed steroid pre-med with my Dr. and he never suggested it. It's a pickle. Thoughts dare I ask?

Using IVIG for low immunoglobulin levels is a completely different situation from using it for autoimmunity, or indeed in ME/CFS. In autoimmunity the use has nothing to do with low levels. If immunoglobulins are low then IVIG protects against infection but for the great majority of people with slightly low levels it is almost certainly unnecessary.

 

[Jesse2233]

@Jonathan Edwards happy to agree to disagree with you on the value of clinical experience and patient anecdote.

I am curious what you make of the other IVIG studies I referenced, and how you might conceptialize treating a multifaceted heterogeneous diagnosis if studies do not agree on an evidence based path forward.

Also, given the negative endpoint of RituxME 3, I’d be curious to know your thoughts on the next area of investigation ME researchers should take.

 

[Jonathan Edwards]

If it brings you joy to publicly state that the "raw truth" is that I am not proof of anything, that is fine. I can deal with it because it does not change the incredible outcome that I have had thus far. I should note that you are not my doctor and have never examined or run labs on me and the ones who have (all four respected doctors) believe my improvements are directly related to these treatments (IVIG for 1.5 years and thus far, three infusions of Rituximab).

It does not give me joy to say this. I say it in the hope of making it clear to other patients that they may be wasting tens of thousands of dollars on unproven therapies. Your case is obviously very unusual and indeed I do not know the detail. It does not sound like ME/CFS from what you say - rather as you have said yourself. And we still have to face the fact that there are other reasons why you might have got better. That is the hard reality that scientific medicine has to keep in mind if it is going to produce reliable treatments.

 

[Jonathan Edwards]

I am curious what you make of the other IVIG studies I referenced, and how you might conceptialize treating a multifaceted heterogeneous diagnosis if studies do not agree on an evidence based path forward.

You generate the evidence from decent research, as I did for RA. You don't hand out untried treatments without any monitoring or publication - simple.

Also, given the negative endpoint of RituxME 3, I’d be curious to know your thoughts on the next area of investigation ME researchers should take.

I would spend a lot of effort on brain imaging of various sorts. I would also try and pin down whether or not there is really a metabolic defect. I doubt there is because the symptoms of the illness do not seem to fit but there might be. I would also look at T cells carefully and probably T cell related genetic markers.

 

[JeanneD]

@Ema
We need both. They are not mutually exclusive. I would like good science delivered by caring practitioners.

Of course! As a research scientist myself, I very much value research and its contribution to society. But because I am (was) a researcher, I am also well aware of its limitations.

No research study is a perfect representation of the situation. It is a clue among many clues about a complex situation. It's a close-in look at a limited aspect of the situation. This is particularly true in medicine where the sample set is far from clean or absolutely representative, and the individual members of the sample set are extremely complex with many confounding factors that cannot be eliminated.

We need the best research possible. When the scientific data is severely limited, as it is in ME, clinical experience provides highly valuable data which should not be ignored.

Evidence-based medicine as originally conceived, does not suggest that _only_ DBPC studies be used to inform clinical decisions. It said the best scientific data should be given the most weight. That does not mean ignoring all other data. True evidence-based medicine is about ranking evidence, not tossing 90% it in the trash because it's not gold standard. There is very little truly gold-standard research, especially in medicine where confounding factors are numerous and impossible to control.

 

[Jesse2233]

I would also look at T cells carefully and probably T cell related genetic markers.

Interesting. Not to get too off course, but what are your thoughts on the theoretic therapeutic application of extracorporeal photopheresis in ME?

 

[Gingergrrl]

I say it in the hope of making it clear to other patients that they may be wasting tens of thousands of dollars on unproven therapies.

I got insurance approval for both treatments and my doctor wrote a letter to my insurance company which cited six journal articles backing these treatments. I did not pay tens of thousands of dollars, not even remotely close.

Your case is obviously very unusual and indeed I do not know the detail.

That is my point, and it seems like dismissing my case without knowing the details could make others decide these treatments are not useful when they may indeed help (some) people. High dose IVIG for autoimmunity is pretty well established, at least in the US.

And we still have to face the fact that there are other reasons why you might have got better.

There are not in my case. I was declining to the point that my Endo (who knows nothing re: ME/CFS, and treats my Hashimoto's Disease, and objectively works with blood tests and other markers) told me at the end of 2015, if my breathing and muscle weakness did not plateau and continued to progress, he was afraid I would end up on a ventilator and he had tears in his eyes when he said this.

When I began IVIG in mid 2016, this was the very first thing that stopped the progression and I had tried every med and treatment under the sun from Jan 2013 until IVIG. I kept my expectations and hope low and with each step (from as small as being able to open a bottle of water and cut paper with a scissors, to a year later being able to take a shower and cook meals on my own, to 1.5 years later (now) being able to walk without wheelchair), there is no other explanation. I did not have a relapsing & remitting illness. From the day it started, it progressed and nothing turned it around until IVIG and Rituximab.

I am not cured and the best I can hope for is remission. My MCAS is in remission. While it is better, I still have POTS. I still cannot drive a car or climb up more than two stairs. But I believe I will get there. My family, friends, and doctors are very hopeful, as are all the nurses at my infusion center, and everyone who has seen me. There will be disbelievers like you, but everyone who knows me in person, is in awe at what they are witnessing. I will probably stop posting here soon b/c I don't need to keep defending myself or my experience. But every time I do, people ask me to please continue and if my story helps just one person, it is worth it.

You don't hand out untried treatments without any monitoring or publication - simple.

I guess you just wait for people to die then? And I am not sure what you mean "without any monitoring" b/c in my case, I was very closely monitored with blood work every four weeks and ongoing appts with two doctors. My MCAS doctor (who is the actual prescriber of both treatments so I can do them locally) said that he prescribes IVIG all the time and it is very common for him. He did not see it as a risk as long as I did the pre-meds, 3-day split dose, and very slow infusion speed as a precaution and he was 100% correct. It was as personalized as you could get b/c he has other patients who can infuse at a speed of 300 but my speed is 40. My case actually may be published in a journal one day (with my doctor here and a doctor in Germany both very interested in it). But I am sure you would dismiss that, too?

 

[Jesse2233]

Very true @Gingergrrl

There are probably many other patients out there like you who were given an ME diagnosis and who could greatly benefit from your protocol. Afterall your clinical picture is post-infectious onset leading to “unexplainable” symptoms.

And it’s certainly not a placebo when you literally cannot walk or eat normal food without treatment

 

[RYO]

You generate the evidence from decent research, as I did for RA. You don't hand out untried treatments without any monitoring or publication - simple.




I would spend a lot of effort on brain imaging of various sorts. I would also try and pin down whether or not there is really a metabolic defect. I doubt there is because the symptoms of the illness do not seem to fit but there might be. I would also look at T cells carefully and probably T cell related genetic markers.

They are performing fMRI before and after exercise challenge at NIH Intramural study. Also TMS (transcranial magnetic stimulation). I wish NIH could add PET-MRI.

Cytophoresis already performed. NIH is looking very closely at T cells. They recently added skin and muscle biopsy. They are planning mitochondrial genetic studies on muscle tissue.
Metabolic studies being performed using Seahorse analyzer.
Also mass spectrometry and other studies to look for autoantibodies on CSF samples.

 

[Gingergrrl]

Very true @Gingergrrl There are probably many other patients out there like you who were given an ME diagnosis and who could greatly benefit from your protocol. Afterall your clinical picture is post-infectious onset leading to “unexplainable” symptoms. And it’s certainly not a placebo when you literally cannot walk or eat normal food without treatment

Thanks @Jesse2233 and I know that you understand as you have met me, you have also researched every treatment known to man to try to figure out what could improve your symptoms, and you are not afraid to take risks to get your life back. Ironically the people who have dismissed my symptoms were never family or friends, nor fellow peers from this board, but were all doctors. And the person on PR who continues to dismiss it is also a doctor.

I have to let it go, this is not worth my energy. At one point I was getting 2-3 new PM's per day from people asking me about my treatments (and I NEVER give medical advice but answer questions re: my own experience). I am now getting 2-3 new PM's per week, which is much more manageable, and the over-arching theme is patients who have been disbelieved, dismissed, or even suffered PTSD/trauma from doctors who did not believe how ill they were. The biggest issue doctors seem to dismiss is allergic reactions to food and meds (although I do not understand why).

I have two amazing doctors who are saving my life. I am NOT anti-doctor even remotely. I just lose patience for doctors who dismiss my case when there might possibly be something to learn from it. I have put endless hours into researching treatments, actually doing the treatments, and responding to every single PM that I have ever received. If certain doctors want to believe these treatments are useless for everyone, they are not listening, but there is nothing further that I can say or do.

 

[geraldt52]

...When the scientific data is severely limited, as it is in ME, clinical experience provides highly valuable data which should not be ignored...

That is where we find ourselves, and where we have found ourselves for decades on end. I do worry that doctors don't follow and document their patients who they prescribe "treatments" to carefully enough, but many do what they feel they can do given the limitations of time and money. Patients and doctors can't be blamed for scrounging for crumbs when that's all they have. We can thank the CDC, and until recently the NIH, for all of this, as they've stigmatized the illness and provided no money or incentive for anyone to study or treat it.

 

[RYO]

That is where we find ourselves, and where we have found ourselves for decades on end. I do worry that doctors don't follow and document their patients who they prescribe "treatments" to carefully enough, but many do what they feel they can do given the limitations of time and money. Patients and doctors can't be blamed for scrounging for crumbs when that's all they have. We can thank the CDC, and until recently the NIH, for all of this, as they've stigmatized the illness and provided no money or incentive for anyone to study or treat it.

It's a perfect storm. A devastating illness that leaves you powerless to advocate for yourself. An illness that is invisible to conventional medical testing and a modern society that has weakened the fabric of family life.

If the NIH Intramural study for ME/CFS fails, we are truly screwed...

 

[Jesse2233]

If the NIH Intramural study for ME/CFS fails, we are truly screwed...

There is still the prospect of individualized and multi-pronged treatment from doctors willing to dig deep

 

[Learner1]

Personalised medicine has nothing to do with handing out unproven treatments and relying on subjective accounts of benefit. It is to do with tailoring drugs based on scientific evidence.

Actually, this view is a bit narrow. There's a lot of work being done in personalizing medicine, which goes far beyond matching up drugs to patients with particular diseases. It's an evolving field, but this gives an idea of the philosophy behind personalising medicine, which seems to track with what many of the ME/CFS researchers are doing:

http://p4mi.org/what-we-do

If you read my papers you will see that I paid detailed attention to personalising the use of rituximab in relation to autoantibody profiles and other things.

Sorry but I am insulted to be criticised from a position of complete ignorance of my work.

I've read them. You seem to be in complete ignorance of my reading list. I'm just a patient trying to find a way to wellness and read a lot of medical journals, textbooks, etc. in pursuit of a cure.

There are many potentially beneficial treatments out there. The challenge is figuring out which patients may benefit, when in the treatment process they might benefit, and dependencies and cofactors needed for success.

This is a very complex disease and most doctors and researchers don't have the patience, creativity, curiosity, and persistence to help us, which is why patients are dismissed and mistreated by many doctors.

Evidence-based medicine as originally conceived, does not suggest that _only_ DBPC studies be used to inform clinical decisions. It said the best scientific data should be given the most weight. That does not mean ignoring all other data. True evidence-based medicine is about ranking evidence, not tossing 90% it in the trash because it's not gold standard. There is very little truly gold-standard research, especially in medicine where confounding factors are numerous and impossible to control.

This is very true. We need progress on all fronts, and as in the war on cancer, doctors who are creative and willing to try new treatment approaches.

 

[Nickster]

I am teleconferencing with Dr Chheda tomorrow and will bring this up to her and get her input. In the past she said that parovirus is difficult to treat. My son did test positive for cocksackie b as well.
Thank you for your information!

Dr Chheda was encouraging IVIG and starting off very slowly. So we will see we're this takes us. The treatment plan is still forming with the group of docs.