Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study - 2020 - Rekeland, Mella, Fluge et al

I dont know how u can reach the conclusion that "They were mildly improved at best" after reading this study

I mean look at the graphs https://www.frontiersin.org/files/Articles/502145/fmed-07-00162-HTML/image_m/fmed-07-00162-g003.jpg

Any of those jumps for me in functioning level would be HUGE even if i didnt recover completely.

Edit: Also, what u say about rituximab is not factually correct. I was a moderator for one of the fb-groups where hundreds tried rituximab, and only 10-20 had serious side effects, usually a worsening of ME due to overexertion.

 

I think this is an unhelpful generalisation. Having treated many chronic diseases with many drugs I would say cyclophosphamide is the one I would be most keen to avoid. Bladder cancer is one of the most awful things to cope with -often over many years. Rituximab may produce lethal side effects in one person in about ten thousand. For cyclophosphamide the long term chance of cancer may be as high as one in twenty.

In autoimmune disease in general cyclophosphamide has become almost obsolete because physicians pretty much all feel the same way. If cyclo can help then something more specific and less directly toxic should do the job much better. And more specific drugs are available.

Unfortunately I do not think the results of this trial tell us anything at all. The cruelest irony is that Drs Fluge and Mella are such committed, trustworthy and sympathetic physicians that I strongly suspect the motivation for patients to say they are better is far more powerful than in a trial of psychotherapy.

 

Rituximab is a very safe drug taken in isolation (not with other immunosuppressives), contrary to what many claim here. All the serious adverse effects in phase 3 were treatble infections and gastrointestinal events. To put things in perspective the placebo group had around 16 SAE`s and the rtx group 30.

 

It is for sure not higher than 5 perc with CCC, im not gonna bother having a technical argument about this sorry.

 

As the person who introduced rituximab for autoimmune disease I do not actually agree with that @Marky. It quite commonly produces quite major problems, not well documented in the data sheet. And if used by a physician who is not an expert on B cell biology (i.e. many physicians) there is a significant risk of serious immunodeficiency. Early use in France produced a lot of major problems.

But cyclophosphamide is much worse.

 

Which more specific drugs?

Just as an aside; I do wish fluge and/or Mella would be able to come on this forum or there was a way to contact them so we could put these queries and discussions to them.

 

I mean, ill take ur word for it Jonathan, but when reading up on it before trying it, what made me decide to go for it was the very low death rate and mostly treatable infection-related side effects. The scary side effect for me was PML, but that mainly occurred when rtx was taken together with other immunosuppressives.

If there is a side effect profile that is not documented, then I guess thats a problem

 

Anti-B cell drugs for B cells, anti-T cell drugs for T cells, anti-cytokine drugs for cytokines, increasingly bioengineered antibodies or receptor or enzyme blockers - Rituximab, campath, etanercept, tocilizumab, kinase inhibitors - all sorts. Cyclo is just a broad spectrum chemical poison that happens to kill immune cells a bit more than others.

 

The commonest serious side effect is pneumonitis but documentation of this has been consistently glossed over. I have seen two deaths from it - the only deaths in my department due to rituximab as far as I can remember.

 

There is more serious adverse events involved with Cyclophosphamide, notably the neutropenia which makes patients vulnerable to all kinds of opportunistic infections, which can be deadly. It is not a casual drug and i know Jonathan that you know that, something that can be difficult to grasp for unsuspecting and keen patients.

 

Not directly about the study, but interesting to see from the supplementary material Table 2 (link at the end of the article) under previous treatments reported at baseline, 13 patients had previously gone through the Lightning Process.

 

Were they also responders

 

I can't tell from that table, not sure if the information is there?

 

I’d like to see results from CycloME Part B (severe/very severe ME) when available, the sooner the better :

https://helse-bergen.no/en/avdeling...ysikk/research-and-development/cyclome-part-b

 

The Kavli Trust, who has supported this research team over several years with funding, has an article today about this study.

They've written about the research team before, and provided English translations. But for now we'll have to make do with a google translation.

- Although the study alone does not provide a basis for providing cyclophosphamide outside clinical trials, it, along with an increasing number of basal studies, provides another indication that the immune system is central to the disease mechanisms of ME. Therefore, a key focus in the current phase is to better understand the role of the highly complex immune system, comments Olav Mella.

Kavlifondet: Lovende resultater fra forsøk med kreftmedisinen ved ME/CFS
google translation: Promising results from trial with cancer medicine on ME/CFS

 

I very much appreciate the work of Fluge and MeIla and the rest of the team. They’ve done a heck of a job for many years in a professional, cautious and emphatic way. Gained knowledge and also built a valuable bio bank. Hope they’ll stick around, if able to get the necessary funding for future projects.

Had a brief look, but don’t know what to make of the results? Maybe results make way for further studies? I don’t want to spoil any excitement with a minor anecdote, but still thought I could share a little from my personal experience. For what its worth, I know that this drug can be very potent. In my case, unfortunately not for the better. Let’s just say that I am quite the opposite of a responder. Could speculate extensively about the reasons a major deteriration. There could be other co-existing reasons/explanations, as a natural decline per year, a very big permanent relapse in no connection to cyclo and so on. But given the magnitude of the deterioration, it seems quite likely that cyclo must have played a (significant) part. In my case.

I could add for the curious one, that when enrolled, I was a >10 year patient, moderate/severe. Mostly housebound. If I were to describe my course of illness in general terms, it’s been an endless journey of push-crash. Using every neuron of mental strength and going on pushing through as best possible, read: way beyond limits. In the aftermath from beginning of disease to May 2020; if I knew from the start what I knew many years ago, I would NOT have done the same thing over again, the approach of pushing on. And that’s about the only thing I’m sure of after all these years.

Another thing worth mentioning is that I personally have tried to achieve steps almost at any cost, after the idea of trying to maintain some of my rest health, the silent things, the things you don’t necessarily get symptoms from, but that obviously takes a massive blow, when going from active to non-active, such as hypertension, cholesterol, insulin and god knows what. But as we all know, pushing through in every circumstance that requires energy, in this case walking, is the mother of all catch-22’s. You may delay other bad things that comes as a result of inactivity, but the effort, when having to push through it, even if it is very gentle/slow walking, it will often or always make your ME-symptoms (a lot) worse, if being in or close to the so-called severe spectrum. To put it in another way: I have done a whole lot of walking that I should not have done from a ME perspective. That means fighting for every step no matter how hard it may be. If that make any sense? But how is one supposed to choose from 100% non-active and maybe better ME symptom-wise, or just a little active pushing through keeping some rest-health at bay but being in constant PEM? An impossible choice, the classic choice of pest or cholera. In the study they make a point that measuring of steps is not a perfect measurement. Overall definitely a good measure, but yes, it is true that patients for different reasons to some extent can choose how to expend limited energy. It can swing both ways, in my case more steps than any other meaningful activity.

And yup, did LP over a decade ago. Without any real advice, not knowing what to do or where to turn, out of options. But not defeated, taking some kind of personal responsibility? Well, the way wasn’t that long to the «magical» and aggressively advertised LP. End of the LP-story is not a good one, not bothering going into details here.

 

Who the F*** walks 3000 steps a day with me/cfs? And if so, why the hell would you pump that poison in your veins? 3000 steps? Come on people!

 

I have done - a more typical value (if I have to go out) is under half that (total steps from waking to bed), and halving that again is routine (so around 700-850 a day).

I have also walked much further, not without consequences, but much further.

For special occasions I do walk further, or did, before....they made everywhere outside inaccessible, by 'discouraging' use of buses and not allowing people to rest.