Immunoadsorption in Patients With Chronic Fatigue Syndrome Including Patients With Post-COVID-19 CFS (clinical trial started in 2023)

[kushami]

Clinical trial in Germany:

The goal of this clinical trial is to learn about the effectiveness of repeated immunoadsorption intervention in patients with chronic fatigue syndrome (CFS) including patients with post-acute COVID-19 CFS (PACS-CFS).

The main questions it aims to answer are: (1) Does repeated immunoadsorption relieve fatigue and/or other symptoms associated with CFS and PACS-CFS? (2) Is repeated immunoadsorption safe and tolerable in this patient population? What are the side effects of repeated immunoadsorption, and how common are they?

Participants will be asked to participate for approx. 32 weeks (8 months). After screening, participants will receive assigned intervention of either five immunoadsorption treatments (with Ig adsorber) every other day over 10 days or matching sham treatments (without Ig adsorber), followed by a 6-month follow-up period with three ambulatory visits. Every participant will undergo trial outcome, safety, and monitoring assessments.

The results of this study will provide information on whether repeated immunoadsorption can alleviate symptoms associated with CFS and PACS-CFS, as well as insights into the pathophysiological processes in this condition, which in turn can help to develop new and effective therapies.

Estimated completion date: 2025

https://clinicaltrials.gov/study/NCT05710770

https://pubmed.ncbi.nlm.nih.gov/37835071/

 

[Bobby Peru]

FWIW, Here is a rundown of immunoadsorption, albeit from a study directed towards organ transplants.

Immunoadsorption, also known as immunoapheresis, is an adsorptive procedure in an extracorporeal circuit to remove circulating antibodies and antibody complexes from the blood of patients with different immune disorders or rejection reactions [1].

Autoimmune diseases are conditions in which immune responses are directed toward endogenous cells, tissues, and antigens. Formation of antibodies against the body's own tissue may affect nearly all organ systems.

In organ transplantation, the immune system recognizes the transplanted organ as foreign tissue, and the resulting inflammation associated with a rejection reaction can lead to the loss of the transplanted organ.

Immunoadsorption, in contrast to nonspecific plasma exchange, offers the advantage of specificity, that is, only antibodies and immune complexes are removed and other important plasma constituents, for example, albumin and coagulation factors remain with the patient. An accompanying substitution with plasma or colloidal solutions is thus not required. This allows larger plasma volumes to be treated than with plasma exchange, enhancing reduction rates of IgG antibodies or autoantibodies and immune complexes [2], with a low rate of side effects [3].

Immunoadsorption is considered as a therapeutic option in a wide variety of autoimmune diseases and for desensitization before organ transplantation or at acute antibody mediated rejection [4, 5, 6, 7]. It is indicated in all diseases in which circulating, disease‐causing immune factors have been identified to be involved in the onset and progression of the disease. Usually, the procedure is applied in patients in whom other conventional therapies, such as pharmacological therapies, are not successful [7].
Reported IgG reduction was significant in this study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291474/

 

[kushami]

That’s interesting that immunoadsorption can treat a larger volume in one session.

 

[kushami]

I wonder whether the treatment, if successful, will “stick”. Feeling better would be wonderful, but having to have frequent hospital sessions would not be ideal for the patient or the health system.

Still, that’s what people on dialysis have to do, so there is knowledge out there on how to manage this type of treatment burden.

And perhaps patients would only need to repeat the ten days of intensive treatment once a year or something.

Anyway, I really hope it ends up helping somehow!

 

[cfs since 1998]

I wonder whether the treatment, if successful, will “stick”. Feeling better would be wonderful, but having to have frequent hospital sessions would not be ideal for the patient or the health system.

Probably not unless they can stop the process creating the autoantibodies. In the future, they want to do a trial of IA combined with obinutuzumab (similar to rituximab). I wonder if the "inverse vaccine" concept being worked on for MS could be used as well. I also think there is probably more than one kind of autoantibody, so they will have to find all of them.

 

[dankeen]

Most ME patients who benefit from this very expensive treatment relapse within months and some people have been made permanently worse. This could be because of a viral reactivation when there is no antibodies to fight latent virus or it could be because of a rebound effect where a lack of antibodies triggers the body to quickly produce them and more bad antibodies are produced than good ones. In the trial the rebound effect was prevented with IVIG but this is not always done by the clinics who treat ME patients outside of a trial. When treating autoimmune diseases and transplant patients doctors often combine it with immunosuppressive drugs to prevent a rebound effect.

This technology is only worthwhile in cases where antibodies need to be lowered very quickly or the patient will die like transplant rejection and life threatening autoimmune diseases.

IMO Plasma cell depletion is a more sustainable way of lowering antibodies.

@mitoMAN

 

[cfs since 1998]

Most ME patients who benefit from this very expensive treatment relapse within months and some people have been made permanently worse. This could be because of a viral reactivation when there is no antibodies to fight latent virus or it could be because of a rebound effect where a lack of antibodies triggers the body to quickly produce them and more bad antibodies are produced than good ones. In the trial the rebound effect was prevented with IVIG but this is not always done by the clinics who treat ME patients outside of a trial. When treating autoimmune diseases and transplant patients doctors often combine it with immunosuppressive drugs to prevent a rebound effect.

This technology is only worthwhile in cases where antibodies need to be lowered very quickly or the patient will die like transplant rejection and life threatening autoimmune diseases.

IMO Plasma cell depletion is a more sustainable way of lowering antibodies.

@mitoMAN

That is disappointing to hear. I was under the impression that immunoadsorption was selective and wouldn't filter out "good" antibodies? I guess I don't quite understand how it works. It's not available anywhere in the US, anyway.

Even despite the quick relapses, I think it is just more evidence that the immune system is the key to this illness.

I'm also not sure why there is such resistance among researchers to combine immune modulation with antivirals. My pet theory is that ME/CFS results from an immune system that is trapped between fighting a virus and autoimmunity. Seems wise to attack the illness from both angles when antivirals won't solve the autoimmunity problem and immune suppressants won't solve the virus problem.

I can even speculate how each one by itself might make the condition worse. Antivirals could reverse virus-induced immune suppression and worsen autoimmunity while immune suppressants would obviously worsen any viral infections.

 

[junkcrap50]

I always presumed they would give IVIG after IA (ImmunoAdsorption) since it can lower IgGs quite low (like 20-30% remaining).

But with regard to pwCFS, I had thought that the consensus so far was that immunoadsorption does not help everbody, ie some people notice no change in symptoms at any time, not even temporarily. Do I have that right?

IMO Plasma cell depletion is a more sustainable way of lowering antibodies.

What is it exactly? How do they do it? It doesn't seem very common, particularly in research (so close to nonexistent clinically). Also from my little reading, they seem to be wanting to target plasma cell specifically, only those that express a certain autoantibody, but CFS has no autoantibody or plasma cell type to target.

 

[dankeen]

That is disappointing to hear. I was under the impression that immunoadsorption was selective and wouldn't filter out "good" antibodies?

No it is indiscriminate. I think BC007 is the only way to remove specific auto-antibodies. I don’t think anyone has identified all of the bad antibodies anyway. Lupus, Sorjen’s and RA are believed to be antibody mediated diseases, but not all patients test positive for the particular auto-antibodies known to be associated with these diseases.

But with regard to pwCFS, I had thought that the consensus so far was that immunoadsorption does not help everbody, ie some people notice no change in symptoms at any time, not even temporarily. Do I have that right?

That is correct. I think we can conclude that auto-antibodies are only part of the pathology for a subset of pwME.

What is it exactly? How do they do it? It doesn't seem very common, particularly in research (so close to nonexistent clinically). Also from my little reading, they seem to be wanting to target plasma cell specifically, only those that express a certain autoantibody, but CFS has no autoantibody or plasma cell type to target.

Plasma cells can be depleted with CD38 antibodies like Daratumumab and proteasome inhibitors like bortezomib and carfilzomib. There is research into plasma cell depletion for autoimmune diseases that proves the concept. There is only a small (ongoing) pilot trial of Daratumumab for ME conducted by the Norwegians. They announced in 2023 they had completed treatment with six patients and it went well enough they are recruiting another four. This is the only data they have made public and is presumably the best responder.

They discuss plasma cell depletion in three pwME using bortezomib in the below patent.
https://patents.google.com/patent/WO2021038097A1/en

This paper explains the theory
https://www.jci.org/articles/view/1...At-DMv9JV5nSApnllnLeZwCUC2LwyAm4J68-UzCGa_EEw

 

[cfs since 1998]

No it is indiscriminate. I think BC007 is the only way to remove specific auto-antibodies. I don’t think anyone has identified all of the bad antibodies anyway. Lupus, Sorjen’s and RA are believed to be antibody mediated diseases, but not all patients test positive for the particular auto-antibodies known to be associated with these diseases.

Thank you, dankeen. I read about it more, and it can be "selective" for IgG, for example, but not specific antibodies. I understand it better now. So there isn't really a huge difference between IA, plasma exchange, and IVIG.

I think we can conclude that auto-antibodies are only part of the pathology for a subset of pwME.

I think that there could be cycles of autoantibody production, rather than a continuous process. And when autoantibodies are turned on, tissues (endothelium, small nerve fibers, etc.) become damaged. The longer you are sick or the more severe you are, the more damage. So one would need to suppress the autoantibodies for a prolonged time period, to allow the damage to be repaired. This could take several years, if it can be even repaired at all. A lot of treatments for autoimmune diseases, like MS, can only slow progression or stop relapses, but can't reverse or cure the disease completely.