Open [Tokyo, Japan] Study of the Efficacy and Safety for Rituximab in Myalgia Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

The link doesn’t take me to the press release, but a list of many other ones

 

It’s supposed to be a scale to measure the severity of ME/CFS from 9 to 1, and anything below 6 is probably better than mild.

It’s very different to how the scale for FUNCAP works, where most of the scale is within the range of mild to extreme.

 

edited

 

oh sorry i thought it was a general disability scale for government or something

 

I did as well based on the scale, which is why I was surprised to see that it’s for ME/CFS specifically.

 

The full press release auto-translated. Some line breaks added.

—————

About the investigator-initiated clinical trial targeting myalgic encephalomyelitis/chronic fatigue syndrome

　The National Center of Neurology and Psychiatry (Kodaira City, President: Kazuyuki Nakagome, hereinafter referred to as NCNP) will begin investigator-initiated clinical trials of the drug rituximab (recombinant) (anti-CD20 monoclonal antibody, hereinafter referred to as rituximab), which targets B cells, in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who are outpatients at NCNP Hospital. Rituximab is a mouse-human chimeric monoclonal antibody that targets the CD20 antigen expressed by B cells, and due to its efficacy in depleting B cells, it is covered by insurance for malignant tumors (malignant lymphoma) and various immune diseases (vasculitis, scleroderma, etc.) involving B cells.

Development Background
　ME/CFS is an intractable disease that develops due to viral infections and other factors, and can lead to severe exhaustion and sleep disorders that leave patients bedridden or make it difficult to perform the physical activities necessary for daily social life. Although symptoms can improve to a certain extent, patients face many difficulties before returning to society, as symptoms can rapidly worsen due to stressful lifestyles and physical and mental stress.

In addition, because abnormalities cannot be detected by general blood tests or imaging tests, awareness of the disease is low in the medical field or in the general public, and many patients and their families are in extremely difficult situations.

　The NCNP Neuroscience Institute Immunology Research Department has been carrying out a project to build a medical network for ME/CFS (AMED Yamamura group; 2018-2020) and a research project to develop blood diagnostic methods (AMED Sato group; 2019-2021), and has published results that lead to understanding the pathology of ME/CFS and the development of treatment strategies1 )-4) .

In particular, they have been actively researching B cells, a type of immune cell, and autoantibodies, and have confirmed that autoantibodies against autonomic nervous system molecules (such as β2 adrenergic receptors) are detected in more than 30% of ME/CFS patients, and have further demonstrated that the increase in autonomic nervous system receptor-reactive autoantibodies is related to abnormalities in the neural network in the brain.2 )

In parallel ,
　detailed analysis of the antigen receptor genes of B cells suggested that ME/CFS patients are exposed to specific antigens (such as viruses) and are in a state where the immune system is strongly stimulated.3 ) Based on the above, ME/CFS is a neuroimmune disease (a disease with problems that span both the nervous and immune systems), and it is thought that there is a possibility that the indications of drugs used for neuroimmune diseases may be expanded. In response to this, European researchers have published a series of papers supporting the idea that ME/CFS is an autoimmune disease.
　

Currently, B cells are an important research or treatment target in neuroimmune and autoimmune diseases, and a Norwegian research team conducted a clinical trial in which ME/CFS patients were administered the anti-CD20 antibody rituximab, which removes B cells.
　

This clinical trial was planned based on the clinical observation that when rituximab was administered to patients with malignant lymphoma and ME/CFS for the purpose of treating malignant lymphoma, ME/CFS also improved. In a Phase II trial, efficacy was confirmed in 18 out of 29 patients. In a Phase III multicenter placebo-controlled trial, efficacy could not be demonstrated, but at least some patients were shown to respond to treatment. ME/CFS is expected to include a diverse patient population, and it was suggested that rituximab may be effective in specific patient groups defined by biomarkers.

Development details
　This investigator-initiated clinical trial will exploratory compare the efficacy and safety of rituximab against ME/CFS symptoms in 30 ME/CFS patients attending NCNP Hospital using a placebo-controlled double-blind method (primary evaluation period 24 weeks). In the subsequent secondary evaluation period (24 weeks), patients who received rituximab in the primary evaluation period (hereinafter referred to as the rituximab-first administration group) will be administered a placebo, and the onset and duration of the effects of rituximab will be exploratory examined throughout the entire evaluation period (48 weeks).

In addition, patients who received a placebo in the primary evaluation period (hereinafter referred to as the placebo-first administration group) will be administered rituximab in the secondary evaluation period (24 weeks), and changes in evaluation items before and after switching from placebo to rituximab within the same patients will be exploratory examined.
　
In order to identify the rituximab effective group, an exploratory study will be conducted by adding ME/CFS severity classification based on the Performance Status score defined in Japan for symptom evaluation to the evaluation items used in the Norwegian clinical trial, as well as immune biomarkers that may be related to efficacy. In addition, this investigator-initiated clinical trial is expected to make it easier to detect clinical improvement/deterioration than previous clinical trials by using techniques such as having participants record their daily symptoms using an app stored on their smartphones.

Future developments
　It is expected that the results of this investigator-initiated clinical trial will advance our understanding of the pathology of ME/CFS and the development of biomarkers, leading to the development of new treatments that target B cells.

 

This is a terrible description of ME/CFS. It reads more like CF.

This is a terrible description of PEM and the causes. It reads like BPS babble.

4 is this: https://www.s4me.info/threads/free-...nic-fatigue-syndrome-2023-kimura-et-al.33526/

They are aware øf Fluge and Mella’s work.

 

I'd be careful with machine translating from Japanese, even if it reads quite well. A native or near-native speaker might shed more light on this. The concept of the language is very different to English and often 1:1 translation is not possible and doesn't capture the full meaning of the native sentence.

Though to me it sounds relatable to the quite common concept of spoons & battery charge (which I cannot relate to at all).
My impression was that there is a significant fraction of ME/CFS patients where this description would fit.

 

All those arguments might be relevant if we have reason to think that targeting B cells make sense in the first place. With major risks involved I find it hard to see how any of these approaches are justified at present. If I was on an ethics committee I would not approve I study like this, at least from the information I have.

And even for diseases that respond to rituximab I have not actually seen data suggesting that newer drugs make much difference. They are mostly tried on the basis of getting new patents.

 

Seems an indication that they don't understand trial methodology.

 

That I would like to see some evidence for.

 

Sorry guys, but no.

 

That’s fair enough. I gave the first paragraph to DeepL and this is that it returned:

There are seemingly multiple options in the translation. But none of them are very accurate as a description of ME/CFS or PEM. But I’ll hold my judgement for now due to the lack of an official translation.

 

I believe this is the second source in the press release. It’s paywalled.

https://onlinelibrary.wiley.com/doi/10.1111/jon.12751

 

That looks very much like a couple of cherry picked results from presumably dozens of region options and several antibodies. And, as has been said, these antibodies are present in healthy people to much the same level.

 

I wonder if Andrew Lloyd, Vegard Wyller and Alistair Miller will be as outraged this time and write a letter to the BMJ protesting any medical intervention for ME/CFS are an affront to their business model.

 

Certainly.

Based on your posts I know that you're critical to that theory, but at least for me it's the one (an unusual type of functional "autoimmunity") with the most evidence behind (not only talking about ME/CFS papers but based on the whole picture with related diseases e.g. like Post Covid, Fibromyalgia, POTS). Though I'm biased with most of my disease coming shortly after covid vaccines and significant effects of "immune events" (don't want to detail deeper to stay anonymous).

I just hope that long-lived, bone marrow plasma cells are not the main cause (guess these shouldn't be erradicated in a Rituximab way...).

I don't think we can say this yet, since there are still huge unknowns about ELISA vs ELISA, ELISA vs rat-bioassay and rat-bioassay vs humanized-stem cell (?) bioassay (in work at Univ of Erlangen).
Most studies have been based on non-validated ELISA panels from different private labs.

This older article still has a good overview:
https://www-trillium-de.translate.g..._sl=de&_x_tr_tl=en&_x_tr_hl=de&_x_tr_pto=wapp

And based on experiments in cattle & ferrets, we know that infection with Sars-Cov2 can lead to the production of functional GPCR autoantibodies (in cattle & ferrets):
https://www.mdpi.com/2227-9059/11/10/2668

 

What’s that?

 

Cells are not destroyed but activated / blocked by "functional" autoantibodies, cf. the first article of my last post. Google Translate doesn't let me copy the relevant part of the article, it's in the beginning. But there are many other papers detailing this online.