Intravenous Cyclophosphamide in ME/CFS, An Open-Label Phase II Study. (Rekeland, Fluge, Mella, 2020)

[hunter1899]

Should this:

“There were 11 serious adverse events in eight patients.”

be of any concern?

 

[Wishful]

“There were 11 serious adverse events in eight patients.”

Why is the image of a giant mutant parasite ripping its way out of a patient's body what comes to my mind first?

 

[joshualevy]

Should this:
“There were 11 serious adverse events in eight patients.”
be of any concern?

I think that safety is a personal decision, and no one except you can decide what is safe and what is not. However, In the US a "serious adverse event" is one that requires immediate treatment. That is, a non-scheduled / no-appointment trip to a doctor, clinic, emergency room, or admission to a hospital. If you have time to schedule an appointment, the the issue is not a serious adverse event. I'm pretty sure the EU uses similar criteria.

I think a bigger issue with this study is that Fluge and Mella have made exactly the same mistake her that they made with the previous treatment. A no control group phase-II study leads to false hopes for the phase-III study. Researchers have a lot more influence on a no-control group study, so you get a lot more false positives. This is exactly what happened before. Even if they don't learn from their previous mistakes, we should.

 

[jaybee00]

They note the lack of control in the paper. For a further study, the issue is that it’s difficult to blind cyclophosphamide because it makes you sick—patients will know whether they have gotten the treatment or control.

 

[Wishful]

the issue is that it’s difficult to blind cyclophosphamide because it makes you sick

It's easy enough to find things that make people feel sick. I suppose it's a problem finding something that makes the patients sick in an indistiguishable way.

Does cyclophosphamide make people feel as bad as listening to rap?

 

[joshualevy]

They note the lack of control in the paper. For a further study, the issue is that it’s difficult to blind cyclophosphamide because it makes you sick—patients will know whether they have gotten the treatment or control.

Yes, but they didn't even try. An imperfect control group is still much better than no control group at all.
Also the combination of a unblinded treatment and all patient-reported outcomes is particularly bad. Not even PACE was that bad.

 

[jaybee00]

But it was a phase II trial. Phase 2 aren’t placebo controlled.

https://www.cancer.org/treatment/tr...u-need-to-know/phases-of-clinical-trials.html

 

[sometexan84]

I wonder whether the patients had something else in common

Funny you should say that. I think this was the first study where they first discovered those HLA alleles:

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

In that article, what I found very interesting was how those w/ the HLA risk alleles, had the following autoimmune diseases, ordered by frequency:

1) Hashimoto’s thyreoiditis/hypothyreosis
2) psoriasis
3) rheumatoid arthritis
4)alopecia areata
5)Crohn’s disease or ulcerative colitis

The reason it interested me so much, is that I have had 2 and only 2 autoimmune conditions. Those are Hashimoto's, and psoriasis.

Needless to say, I gotta get this testing done. Haven't looked much into where do to these tests yet. I just now that in the test they used HLA genotyping by next generation sequencing.

 

[jaybee00]

@sometexan84

I used these guys https://www.bonemarrowtest.com/

I was happy with them.

 

[sometexan84]

@jaybee00 sorry if you said this already. But did your results show anything significant?

That is a fantastic reference btw. And it's not that expensive.

 

[pattismith]

Should this:

“There were 11 serious adverse events in eight patients.”

be of any concern?

yes, I would like to know if adverse events happened in the non responder group or the responder one.

And also what was the immune profile of the patients with adverse events? MBL level? CD4/CD8 ratios? etc

 

[pattismith]

Funny you should say that. I think this was the first study where they first discovered those HLA alleles:

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

In that article, what I found very interesting was how those w/ the HLA risk alleles, had the following autoimmune diseases, ordered by frequency:

1) Hashimoto’s thyreoiditis/hypothyreosis
2) psoriasis
3) rheumatoid arthritis
4)alopecia areata
5)Crohn’s disease or ulcerative colitis

The reason it interested me so much, is that I have had 2 and only 2 autoimmune conditions. Those are Hashimoto's, and psoriasis.

Needless to say, I gotta get this testing done. Haven't looked much into where do to these tests yet. I just now that in the test they used HLA genotyping by next generation sequencing.

...interestingly, Association between HLA DQB1*0303 and central nervous system affection in Sjogren has been reported!

So I wonder if the DQB1*0303 subset Fluge and Mella found may have been SS...

View attachment 41659


Oxford Textbook of Sjögren's Syndrome - Elizabeth J. Price - Google Books

Also HLA-C*07 is a risk allele for Psoriasis at the IMD laboratory and I am homozygous for it;

(neuropathy is a known psoriasis associated condition)