IVIG Treatment

[Ema]

I have found subQ IgG replacement (Hizentra) extremely helpful myself. Of all the treatments I've tried, it's one of the few that I've found successful enough to carry on with for years.

Recently I started infusing it once every 3 months at 144g to more closely approximate the high dose IVIG used for autoimmune disease and the results have even been better. It is a pain to infuse that many days in a row, but then it's over for a while. I can definitely tell when it's getting close to time to infuse again.

 

[Hip]

Dr Chia told my son that he liked using ivig, but, it was hard to convince the insurance to cover it.

Yes, that's what I heard also, from watching Dr Chia's Invest in ME London Conference DVDs, that IVIG was usually not covered by insurance. But the impression I got from Dr Chia was that IVIG was sometimes helpful but nothing dramatic. That is to say, he offered no stories of severe bedbound ME/CFS patients going back to work after IVIG; whereas for his oxymatrine treatment, he does relate such stories.

This Phoenix Rising article provides some info about IVIG treatment:

Chronic Fatigue Syndrome (ME/CFS)/Fibromyalgia (FM) Studies

IVIG therapy cured several parvovirus-B19 associated cases of chronic fatigue syndrome. On the other hand a large place-controlled, double-blinded, randomized Australian trial using a variety of doses found no specific therapeutic benefits. FM patients with evidence of nerve demyelination caused by immune dysfunction responded positively (reduced pain, tenderness, increased strength) to a short-term IVIG trial.

Chronic Fatigue Syndrome (ME/CFS) Doctors Report

Given its expense Dr. Teitelbaum turns to IVIG only after other means of fighting chronic infections have been exhausted. He has, however, found that IVIG can ‘dramatically help’ some patients. Dr Tae Park of Korea uses IVIG extensively and reports high levels of success. Dr. Peterson finds it very helpful in some of his patients. Dr. Chia has found it helpful for fibromyalgia patients.

My son has tested positive for parovirus and I did not realize that ivig helped patients with this condition.

I think your son would have to have an active parvovirus B19 infection (ie, high titers to the virus) for IVIG to work for that virus, not just parvovirus B19 as a past dormant infection.

ME/CFS caused by active parvovirus B19 infection is quite interesting, as there is a clear link between the viral infection and the ME/CFS symptoms the infection produces, because in the case of parvovirus B19, there is viremia (the presence of the virus in the blood), which you don't get with enterovirus or herpesvirus ME/CFS.

In fact Dr Jonathan Kerr thought it might be good to study parvovirus B19-induced ME/CFS as a viral model to understand the other more common forms of ME/CFS, the enterovirus-associated ME/CFS and herpesvirus-associated ME/CFS, in which there isn't any viremia.

 

[Nickster]

Yes, that's what I heard also, from watching Dr Chia's Invest in ME London Conference DVDs, that IVIG was usually not covered by insurance. But the impression I got from Dr Chia was that IVIG was sometimes helpful but nothing dramatic. That is to say, he offered no stories of severe bedbound ME/CFS patients going back to work after IVIG; whereas for his oxymatrine treatment, he does relate such stories.

This Phoenix Rising article provides some info about IVIG treatment:






I think your son would have to have an active parvovirus B19 infection (ie, high titers to the virus) for IVIG to work for that virus, not just parvovirus B19 as a past dormant infection.

ME/CFS caused by active parvovirus B19 infection is quite interesting, as there is a clear link between the viral infection and the ME/CFS symptoms the infection produces, because in the case of parvovirus B19, there is viremia (the presence of the virus in the blood), which you don't get with enterovirus or herpesvirus ME/CFS.

In fact Dr Jonathan Kerr thought it might be good to study parvovirus B19-induced ME/CFS as a viral model to understand the other more common forms of ME/CFS, the enterovirus-associated ME/CFS and herpesvirus-associated ME/CFS, in which there isn't any viremia.

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!

 

[Gingergrrl]

Are there other PWME on the board who actually got better with IVIG besides Gingergrrl?

I have had many people PM me who have benefitted from IVIG and just in this thread alone, we have myself, Learner1, and Ema. I belong to two private IVIG groups on FB and one of them is called "IVIG saved my life" and I can honestly say that this has been the case for me.

We have evidence of absence of an effect for IVIG - from at least one formal trial that failed to confirm an effect.

I have no doubt that there were IVIG trials which were not effective, and I am not even sure what this means anymore since the PACE trial is shown as effective. My mast cell specialist, who is an extremely well respected allergist and immunologist, has had many patients go into complete remission from MCAS from high dose IVIG and this is exactly what happened to me approx 1.5 years ago. It also returned my muscle strength back to about 90% normal and eliminated many long-standing symptoms.

But then it reached a plateau that was only broken 2-3 months after I did Rituximab. I am not promoting any treatment for anyone but am telling my story b/c I believe there is a group of us (either a sub-group or a misdiagnosed group) for whom these treatments are life-changing and I cannot believe that I am the only person on earth in that category. I actually know I am not b/c of the number of people from this board, and my IVIG and autoantibody groups, who have had similar experiences to me.

If I had their permission, I would post their stories but most do not want to be put under the scrutiny that I am willing to accept if my story can help someone else down the line. I took my dog to the vet today without a wheelchair (minus I did not drive the car) and with the level of severe POTS and dyspnea/angina that I had prior to IVIG and Ritux, I could not stand up without a wheelchair for more than 30-60 seconds for 3+ years. If people want proof, I am the proof.

My ME/CFS doctor, who is associated with one of the new US Centers of Excellence, explained that likely Epstein Barr had caused the weird antibodies he'd found in me. One month later, at the OMF Stanford symposium, the researchers said the same thing. Not sure it's bullshit.

Thank you @Learner1, and we have the same doctor, and I find it so disrespectful for another doctor to refer to him, or his colleagues, as "bullshit" without knowing the full details.

It is becoming quite clear that ME/CFS is an umbrella diagnosis with patients who share symptoms but who may have different underlying causes, biochemistry, and comorbidities. Mady Hornig did a nice job of explaining this in her talk last month in Norway.

I agree it is an umbrella diagnosis with endless causes (virus, bacteria, mycotoxins, other physical stressors to the body, etc) as well as various co-morbidities (POTS, MCAS, EDS, Lyme, etc).

There are a few patients who have been helped by Rituximab. There are many who haven't. There are a lot of unanswered questions. I was struck by this presentation at this year's Immune Deficiency Foundation conference, where, beginning at 1:00 the use of Rituximab, Bortezomib, and plasmapheresis are used as newer strategies to attack autoimmunity in dysfunctional immune systems.

Thank you for posting that presentation re: how Ritux and Bortezomib as well as PP are being used to attack autoimmunity. I think Dr. Jill Schofield's presentation from "Dysautonomia International" is also excellent in explaining how this works in POTS and other conditions.

Autoantibodies of some sort are present in a high proportion of normal people.

I agree that there are many healthy people who will test positive for autoantibodies but I am not sure this is true for ALL autoantibodies, especially the paraneoplastic ones. I was tested by the head Neuro at Stanford (in a one-off consult and he is not my doctor) and he sent the blood to Mayo Clinic and absolutely insisted that everything would be negative but then I was positive for two autoantibodies. The first thing he recommended was high dose IVIG.

It is also crucial with some of these autoantibodies to check for the cancers that they correlate with (in my case small cell lung cancer) and my doctor takes this very seriously and orders the scans (which so far have all been negative). While other autoantibodies that I have are not dangerous (like the two Hashimoto's abs), they led to me being put on thyroid med and being monitored 3-4x a year. I do not see how autoantibodies can be discounted, and the only way to know you have them is through testing.

The reason why autoantibodies arise is as far as we know nothing to do with infections but rather a spontaneous random process that relates to the spontaneous random nature of antibody genesis as a whole.

My doctor feels differently, and I understand that doctors disagree as I encountered many on my search in the last 4+ years. But I do not understand publicly referring to another doctor's ideas as "bullshit".

Sure, rituximab is useful in all sorts of autoimmune conditions . But as far as I know it has never been shown to work where there is not other good evidence for autoantibodies - moreover it makes several T cell mediated disease worse.

This is the point I am trying to make, that in cases of proven B-cell driven autoantibodies, high dose IVIG and Ritux can be helpful. I agree it is not the right course for a T-cell mediated disease. It is easy to dismiss treatments as "high risk" when you are totally healthy and able to live a normal life. But once you have lost everything (in my case this included the ability to walk without wheelchair, to breathe, and to eat food without anaphylaxis) you view things in a different light.

On this site, the have been a number of patients who were leading normal lives, got a viral illness, became horrifically ill, and after a journey through doctors offices and hospitals, doctors identified strange auto antibodies which seemed to me causing their symptoms, and then underwent treatments like high dose IVIG, Rituximab, Bortezomib, etc. and their symptoms reversed.

This is exactly what happened to me and you could be explaining my case. I had a normal life with a 16 year very successful career. I then had three immune triggers back to back (med reaction, severe mono from EBV, and toxic mold exposure) and then a final respiratory virus which two weeks later led to POTS and I never recovered. I was horrifically ill as you said and it was not until the autoantibodies were discovered in 2016 and I began these treatments, that I started to recover. I had tried two anti-virals and everything under the sun which either had no effect or made me worse. (I am not discounting anti-virals, only that they did not work in my case).

 

[mrquasar]

One can sit around reading studies, or one can be an N=1 study and work with a doctor to personalize care.

That makes it sound so easy. But if you're already moderate/severe and have had bad reactions to medicines in the past, it is a HUGE gamble to put a new compound in your system with no idea what will happen.

I've taken that gamble several times, and every time had a bad reaction. A couple of these reactions took months to fully clear.

At this point I can't afford to gamble on any new treatment unless there really is legitimate science to back it up. The stakes are too high for me. I can't be non-functional for very long if it goes wrong. I have no safety net to fall back on.

 

[JeanneD]

And, here in the US, we need to convince our insurance that we need an expensive treatment like IVIG. My doctors did all the appropriate testing and submitted it along with an appropriate ICD10 code, and it was approved. Not everyone on this site will be able to do this, but I've noticed there are others around here in the very same situation who have also benefited from it.

Put me in that club. I had the appropriate testing. IVIG was recommended by my ME specialist and my hematologist. It was approved by my insurance, which does not happen with an expensive treatment like IVIG unless the evidence for it is beyond question. I, too, am benefiting from IVIG.

I think it is disingenuous to suggest that just because a particular treatment is not effective for some patients, it is inappropriate for all ME patients. This is especially true given the different and sometimes wildly divergent diagnosis criteria used in ME/CFS. Any single research study cannot be said to be fully representative of all ME patients.

Any good scientist knows that a single study is not a sound basis from which to draw a general and universal conclusion. This is particularly true with ME where there is not a single clear diagnosis criteria and the illness may actually be a number of different conditions currently grouped under the same umbrella.

 

[Jonathan Edwards]

It was approved by my insurance, which does not happen with an expensive treatment like IVIG unless the evidence for it is beyond question.

You have accused me of being disingenuous, which I think is disrespect because it implies being deliberately misleading. I may be wrong but I am certainly not deliberately trying to mislead. The above quote seems to me closer to being disingenuous because we all know that there is no reliable evidence about this - nobody is quoting any here but instead clutching at straws about individual cases and no universal conclusion...

Good scientists routinely take note of a single study if it is set up to confirm or disconfirm a series of prior studies of doubtful quality - as is the case here and as is the case for rituximab phase 3. If someone specifically sets up a study to confirm and it fails that is usually taken as pretty good evidence for not much to find. And that is why studies of IVIG in ME stopped.

There is absolutely no evidence for individual responses if there is no overall response in a blinded study.

There may indeed be some people who have been given the diagnosis of ME/CFS who in fact have an autoimmune disease but IVIG is of no proven use in most autoimmune diseases.

If patients want serious scientists to take an interest in ME they need to realise that personal experiences of feeling better with treatments are of no interest to rigorous science, other than as triggers to doing proper studies. Everyone knows that in reality, but it seems it has to be repeated.

 

[Jonathan Edwards]

If people want proof, I am the proof.

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.

 

[Jesse2233]

There seem to be several paradoxes here that can be resolved by accepting that ME/CFS is a heterogeneous disorder with many subtypes as John Edwards has previously stated. Luckily the work that Drs Davis, Lipkin, and Nath are doing may soon lead to a better understanding of what those subtypes are.

Also, it’s an open secret that high dose IVIG works in many (though not all) cases of ME/CFS. Yes Lloyd’s second study was negative, but you should also consider Rowe’s study, Lloyd’s first study, and the clinical experiences of Drs Chia, Chheda, Kaufman, Peterson, Park, and Frid along with the patients reporting results on this forum. A very visceral example is the Norwegian documentary Perversely Dark. A completely bedbound young woman with mono induced ME recovers completely with SCIG (while another patient does not). You cannot in good conscience (or for that matter with a critical mind) watch that documentary and say her response to SCIG was a placebo.

The same is likely true of rituximab though to what degree we do not yet know. What we do now know is that when you lump a significant amount of patients together with symptoms matching Canadian Consensus Criteria they do not show collective benefit from rituximab beyond that of a similarly matched control group. That is not proof it has no benefit for individuals with unique clinical profiles who happen to have a ME diagnosis because no other disease could be identified that explains their symptoms. That said there are cautionary tales such as the German soccer player Olaf Borden with ME who got much worse after receiving rituximab.

 

[Learner1]

If patients want serious scientists to take an interest in ME they need to realise that personal experiences of feeling better with treatments are of no interest to rigorous science, other than as triggers to doing proper studies. Everyone knows that in reality, but it seems it has to be repeated

Your "rigorous science" of studies is problematic.

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.

Having reacted badly to different drugs that worked well on other people and had a stage and type of cancer that I didn't fit the profile for, which puzzled my oncologist to no end, it became clear to me that relying on studies of other patients was a bad strategy for me, especially when it seems that my cancer treatment whacked my mitochondria and immune system, triggering my ME/CFS, when other patients with the same treatment didn't get ME/CFS.

"Personalized medicine" has gotten a lot of press recently, where it is recognized that patients with the same diagnosis have underlying differences making certain treatments a better choice for them than for other patients. In the cancer world, carefully matching treatments to patients based on their genetics, tumor characteristics, etc. is becoming common practice, especially with lung and breast cancers, but others, too.

What we need are studies on methodology of diagnosing and categorizing patients and matching them with personalized treatments, not overly simplistic "one size fits all" treatments that don't really fit a bunch of unique patients. (A lot of people die every year taking drugs as prescribed by their doctors for the FDA approved diagnosis.)

It's more complex to do. and inconvenient for pharmaceutical companies who do a lot of research - their interest is getting their drug approved for a particular diagnosis to make billions. This is how drugs with very little advantage over simple lifestyle interventions get approved... they don't test the lifestyle intervention, they just test drug vs placebo, then publish the results with great fanfare and send armies of sales reps to share the good news about their profitable product while the promising lifestyle interventions are ignored.

And a lot of published research is on male patients only, which means that if you're female, your results can be quite different. (Statins are a good example. Viagra and testosterone, too...)

The best we can hope for as patients is for there to be a plethora of research out there on every conceivable topic, then to read it all picking out those which are the best match to the patient's idiosyncrasies and the situation at hand and interpolating between them to make an educated guess for what will work best for a particular patient.

 

[Jonathan Edwards]

There seem to be several paradoxes here

I do not see any paradoxes, just the usual problems of poorly conducted research.

Also, it’s an open secret that high dose IVIG works in many (though not all) cases of ME/CFS.

All we have is anecdotal hearsay and some inconclusive studies. 'Clinical experience' counts for nothing, as we learnt in the 1970s. I have no problem in watching the Perversely Dark documentary and considering that improvement following IVIG is most likely not due to any specific action of IVIG. This is something I have come across routinely as a physician doing treatment trials over the years. I doubt you have ever been in that position. People are often convinced they have improved because of a treatment when there are very good reasons to think they have improved for other reasons. This is just basic science quality control that every student gets taught.

The same is likely true of rituximab though to what degree we do not yet know.

The rituximab studies are interesting because they demonstrate just how easy it is for results to be biased by hope.

In the first blinded phase 2 study neither the physicians nor the patients knew when an improvement should be expected or how long it might last. The results from that study were all over the place. My main misgiving about the result at six months being significant was that there was no pattern to the improvements.

Then in the open label extension both the physicians and the patients had been made aware by my letter to PlosONE that improvements in other autoimmune disorders tended to begin slowly and last for the six month period of B cell depletion or maybe longer. The patterns of improvements in this open label study were often very similar - following exactly what was predicted with relapse after about six months.

Then with the further blinded study (phase 3) there was no difference between rituximab and placebo.

What this shows is the irony of having very careful sympathetic physicians forming close relationships of trust with patients - the placebo effect climbs steeply. The difference between Drs F and M and others is that they mix their care and attention with scientific rigour and admit that they have fund the drug to have no effect.

 

[Jonathan Edwards]

"Personalized medicine" has gotten a lot of press recently, where it is recognized that patients with the same diagnosis have underlying differences making certain treatments a better choice for them than for other patients.

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.

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.

 

[PinkPanda]

'Clinical experience' counts for nothing, as we learnt in the 1970s.

No, clininical experience is evidence that needs to be further investigated, analyzed and understood. Then, when you have more of a feel for/ understanding of the matter and effects at hand, you can conduct a trial, which might bring proof.

 

[Jonathan Edwards]

No, clininical experience is evidence that needs to be further investigated, analyzed and understood. Then, when you have more of a feel for/ understanding of the matter and effects at hand, you can conduct a trial, which might bring proof.

Presumably you have not been reading the posts. This is exactly what I have said in full previously in the sense of clinical experience without scare quotes. But 'clinical experience' with scare quotes is a phrase specifically used by clinicians who cannot be bothered to do things properly these days. Physicians who do things properly avoid using the term.

 

[jpcv]

@Jonathan Edwards many issues here related to the ME definition, clinical care and medical research.
First, I fullfil many ME criteria and I have rising ANA titers ( 1/320 now) and high CMV IgG \titers.
can we say that I have an auto immune disease? Or my ANA titers are just some random finding?
How can we curently define that a disease is an auto immune one ?
Thank you.

 

[Jonathan Edwards]

@Jonathan Edwards many issues here related to the ME definition, clinical care and medical research.
First, I fullfil many ME criteria and I have rising ANA titers ( 1/320 now) and high CMV IgG \titers.
can we say that I have an auto immune disease? Or my ANA titers are just some random finding?
How can we curently define that a disease is an auto immune one ?
Thank you.

To be able to define an illness as autoimmune one needs to have evidence of autoantibodies and a reasonably convincing story about how those antibodies are producing symptoms. For lupus we have had that for fifty years - we can find immune complexes and evidence for direct antibody attack on cells. For RA the story really only became clear around 1996 with the realisation that small immune complexes will cause cytokine release in joints rather than complement fixation in kidney glomeruli. For thyroid and gastric parietal cell antibodies the story has been easy for a long time. For the other ANA related disorders things remain unclear but the fact that people get better if their antibodies are lowered by rituximab is pretty good evidence.

For ME at present we do not have any such story. One of the problems is that ANA almost certainly cause fatigue but it is not easy to pin down. People with fatigue and high titre ANA should maybe be considered to have ANA-fatigue syndrome, not CFS, but there is no obvious way to draw the line. And a small number of normal people have high titre ANA that does no harm at all. So it remains a grey area.

 

[PinkPanda]

@Jonathan Edwards
Yeah, sorry I hadn't read all of the posts word for word. I tried now, but please correct me if I missed something.

I honestly don't have much appreciation for the approach of using extensive trials to figure out a disease. To me it seems a bit naive, to try and solve a disease by asking one question that a trial can answer/ testing one single hypothesis. Many diseases seem more complex than that.
But I guess that's how medicine often works, you try some medications in hope for the magic bullet, often without having really understood the disease or having a clear idea on how the medication might affect it.

Some helpful medications have been found with this approach, but I don't think you get around getting a better understanding of disease mechanisms, subgroups,..in some illnesses.

People with fatigue and high titre ANA should maybe be considered to have ANA-fatigue syndrome, not CFS, but there is no obvious way to draw the line.

There is no thing like ANA-fatigue syndrome, is there? So people with high ANA are probably also in the CFS umbrella.

Would you see a chance of medications like IVIG, rituximab having an effect for these people? Would you think autoimmunity plays a role in these people?

 

[Jonathan Edwards]

There is no thing like ANA-fatigue syndrome, is there? So people with high ANA are probably also in the CFS umbrella.

Would you see a chance of medications like IVIG, rituximab having an effect for these people? Would you think autoimmunity plays a role in these people?

Oh sure, there are people with ANA-fatigue. People with so-called primary Sjögren's syndrome can have an ANA (Ro in this case) and terrible fatigue and maybe some dryness of the eyes and mouth they might not have noticed much. In any lupus clinic there will be a substantial minority of patients who do not fully fit the diagnostic criteria but have ANA and fatigue and maybe some suggestive features. Whether these people get put under a CFS umbrella I think depends on the approach of the physician.

RItuximab might be expected to help people with genuine ANA-fatigue (in the sense of an illness where the fatigue is due to ANA). However, sadly, the sorts of ANA that produce fatigue look to be the ones that do not shift with standard rituximab therapy - things like Ro, Sm, RNP. Rituximab can have a major impact on kidney and blood involvement but not so much for fatigue I suspect, although a lot more work could be done on that.

 

[PinkPanda]

So there are cases where people with high ANA suffer from fatigue, but a clear cause for the high ANA cannot be pinned down, and they get sorted into one or another disease?

I don't know whether your posts are messy or my head, but this subject is making me dizzy

Rituximab can have a major impact on kidney and blood involvement but not so much for fatigue I suspect, although a lot more work could be done on that.

But then
a) a number of people with high ANA and fatigue get sorted into ME/CFS, since there is no own condition like 'high ANA and fatigue but not clearly fitting into any known autoimmune disease' (that's what I meant with there is no ANA-chronic fatigue syndrome, as in an own condition for people who don't fit into other autoimmune diseases).
And b) You suspect rituximab doesn't have an effect for fatigue? Then that isn't sure?

So can we be sure that not people with some autoimmune processes going on, that have been grouped into ME/CFS, might have reacted to Rituximab?

Does high ANA indicate autoimmune disease only for these certain identified diseases or might it also indicate ongoing autoimmune processes in general?
Because that seems a little going in circles. As long as you haven't identified a condition it indicates nothing and then, when you have identified it, it's an indicator?

 

[Jonathan Edwards]

Because that seems a little going in circles. As long as you haven't identified a condition it indicates nothing and then, when you have identified it, it's an indicator?

It isn't so much indetifying a condition as identifying a plausible causal link between the antibody and an effect on a tissue or organ system. We presumably always have to assume that even some people with obvious autoimmune disease have additional irrelevant autoantibodies in the way that normal people do but since those are relatively uncommon they probably do not cause too much confusion.

There is no doubt that the whole thing is very confusing. Most rheumatologists do not really know how to make sense of it. I spent my entire career trying to pice together the evidence for rheumatic autoimmune disease and ended up with a reasonably clear picture but it took me the best part of twenty years.