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

Difficult to imagine we suffer from the same disease, I cant sit up for 2 mins, for 3 years now.

 

I've worn a device for a few months and it's clear that the step counts are exaggerated because of arm movements, add up about 50% more I'd say, so real counts would be closer to 2K than the reported 3K. This is surprisingly little, this is about what I was doing (between 2K and 3K) during a period of very low activity being housebound and not doing much.

The real difference is not to the norm, of about 5K, but with the maximum. This 2K-3K is pretty much the maximum I could have done, at least sustained. Meanwhile a healthy adult of my age would have no problem going all the way to 15K or even more. That's the significant factor here, the averages are a bit misleading since for the most part, even working adults aren't much more active than a highly sedentary person. They can do a lot more if they choose to, but a typical day isn't super high above what a housebound energy-limited person can do.

Of course this is even more pronounced for those who are mostly bedbound, but those are almost never tested for, always ambulant users. Which is a pretty big gap in both research and clinical settings.

 

Exact same here. Although I've since migrated from cardigans to hoodies . I'm actually grateful for this feature to monitor my activity, rather than a step counter that only counts after the first 16 steps or so like other monitors.

 

If anyone needs a few thousand extra steps, without all the tedious walking, or finding someone 'trustworthy' who will do them for you, then make a roux.

Steps just fly on, far faster than the amount of whisking would suggest, must be something in the movement.

Offhand I can't think of any pwME who need to get their measured step count up, but assuming such a person exists......

 

There is a wide range of severities between people with ME, and within the history of many individuals with ME. My own ME has gone from mild and being able to work part time with great difficulty and lots of crashes, to mostly bedbound. From my experience I'd say I have had the same illness throughout, but at varying severity levels.

That sums it up nicely for me as well. And I’m quite confident that the continuous push-crash cycle that so many patients experience, often are main cause for a negative progressive development. For a long time and by May 2020 housebound and in something like constant PEM, therefore also mostly bedbound, approx 22-23 hours a day. Time left mainly spent standing, sitting, being in an upright position at home. Walking to bathroom, walking to kitchen, maybe sitting upright for a short while to relieve back. But standing and sitting are especially difficult. So it is literally all about sustaining life. And then I give it a go with great consequences when trying to walk around the house. Maybe that adds up to somewhere between 2-3K, and I can agree to the fact that the activity tracker that count more steps than actually taken.

Taking approx 2K steps a day can be called «mild», but what that says more than anything else, is how useless this these labelings mild-moderate-severe-very severe actually are. ME-patients can probably understand the nuances, but I think this labelings are very inaccurate and very unfortunate for people outside. But that’s another discussion.

 

https://twitter.com/user/status/1256924754386341888

 

I'm not sure why the authors mentioned doing a controlled study in the future. I thought that we had discussed in an earlier thread that it would be impossible to develop a control for a cyclo study due to the nausea induced by cyclo. @Jonathan Edwards recommended a dose response study instead here https://www.s4me.info/threads/and-w...ide-study-is-positive.7351/page-3#post-202250 So they could do a blinded multicenter dose response study with maybe 5 different concentration levels of cyclo and maybe anticipate that you would see a response at the higher levels of drug administration, but not at the very lowest levels?

 

So an increased level of motion activity not necessarily correlated with steps?

Like going to outpatient visits for cyclophosphamide?

 

That seemed to me to be the most practical option.

 

Im surprised theres been so little talk about this publication, 9 people went back to studies/work, and then the rest of the responders might or might not have gotten a placebo effect/other bias, potentially pulling the sf-36 mean score down.

I see so many ME/CFS-studies written about that goes viral, when theres just a random finding being sold as the cause for ME, or treatment x as the cure. Here we actually have a study with objective markers, and apparant prolonged responses, and still I havent seen one article on the net other than from the trust that financed the study.

Are we really that pessimistic after the rituximab-studies?

 

Super-liking the comment above from Marky.

It's been like crickets. And it's possible that a Phase 3 trial may not give much more useful data given the issues associated with blinding cyclo, a nausea inducing drug.

There is a suggestion to try alemtuzumab (Campath) in lieu of cyclo for t-cell destruction. But there may be something specific to the cyclo treatment that would not be treated by alemtuzumab. Additionally, the side effect profile for alemtuzmab is not really benign (from Wikipedia):

 

Also, supposes that the cyclo actually worked (not a placebo effect). If you have progressive MECFS, and you wait 5+ years for the Phase 3 study to be completed, by that time you may have progressed to severe. This study indicates that cyclo did not work for the severe patients--so it's possible you may miss your window of opportunity for treatment by waiting. This point obviously doesn't apply to people with improving-MECFS.

 

I was hyped after the Ritxumab trail. I talked to a doctor and paid out of my pocket. It did nothing for me. I followed the autoimmune way over years now for Cfs. I tried MTX, 6 months cortisone, 1 month of sirolimus, 7 plasma exchanges. Im just done with it. The autoimmune part of Cfs is a beaten dead horse to me. Maybe its a part of this disease, maybe its not. Its definitely not useful for a lot of ppl to try and treat it this way. The placebo outcome for the phase 3 ritux trail was better than Cyclo now. So yeah, im not impressed. MTX studies for Cfs made ppl worse overall. ivig studies are all over the place and also mostly negative. I just moved on to look for other ways of treatment than nuking my body with WW1 war crimes. I hope Dr. Prusty's mitochondria study is repeated in another lab soon and i can get my hands on things like SS31 or Mdivi1/P110 and so on.

 

I don’t know why there hasn’t been much publicity, but from my view I do feel pessimistic after Rituximab. And honestly I’m not generally a pessimistic person. This was trialled on mild or mild/moderate population. A proportion had steps increased after trial - but in ritixumab a similar proportion also seemed to have been helped, which was then shown to be placebo when it got to Stage 3.

People do get better from ME for no reason at all sometimes. I think fluctuating illness is not uncommon. And it doesn’t always have to be due to the drug.

I’m also not so excited because of the fact this is a chemo drug, and chemo even for the normal population - makes them often feel dreadfully ill. So what would it do to those with ME? Particularly severe ME. I understand all drugs have side effects but if it’s a good enough drug it’s worth taking. But as Trish pointed out, ritixumab had similar results at this stage in their trials too. So it doesn’t seem to be a good enough drug.

 

"The autoimmune part of Cfs is a beaten dead horse to me" - To you maybe, but we have barely scratched the surface with trying rituximab and looking for some specific antibodies we know of.

"The placebo outcome for the phase 3 ritux trail was better than Cyclo now" - What do you mean by this?

"ivig studies are all over the place and also mostly negative." - Two were positive and two negative to my knowledge

 

"A proportion had steps increased after trial - but in ritixumab a similar proportion also seemed to have been helped, which was then shown to be placebo when it got to Stage 3." - We cant say that for sure for the people who got better in the treatment group, but obviously the people in the placebo group got placebo or spontaneous improvement.

"I’m also not so excited because of the fact this is a chemo drug, and chemo even for the normal population - makes them often feel dreadfully ill. So what would it do to those with ME? Particularly severe ME. I understand all drugs have side effects but if it’s a good enough drug it’s worth taking." - Nobody wants this to be a treatment for ME/CFS, but the most important thing is that it due to its non specific immunsuppression could potentially show us that our immune system is key in the disease mechanism. That would narrow research down A LOT

"But as Trish pointed out, ritixumab had similar results at this stage in their trials too. So it doesn’t seem to be a good enough drug." - Again that's looking at the mean. Im more interested in the fact that 9 people returned to study/school. Of all the acquaintances I have made with ME, almost none has returned to school/work. If 9 out of 42 people of my ME-acquaintances did this I would deem it incredible. I would be interested to see the individual data. I wonder how long these people returned, and in what capacity. I might send them a e-mail, why not

 

I agree. I should have said “no better than placebo”, rather than actually placebo.

I do know of people who have returned to school and part time work. I met a few when I first realised I had ME and went on some of the bigger ME/CFS groups on Facebook. I also met some people at a private clinic I went to, who did alternative treatment/ detox treatment, or drugs.

Some did recover quite significantly; and some who recovered enough to go back to study or school. (No one knows if it’s long term or not yet, and I’m not in contact with them now).

One of the more well-known people with ME, Donna Owens (Yoga, my bed and ME , yoga teacher) fell ill with ME and was moderate and even bed or housebound for quite a few years before becoming well enough to go back to work as a make up artist, for many years, while also being a parent. It’s only more recently she became unwell again, and had a relapse, but now she’s better from that bad relapse and is working from home. She has said on her Instagram thay she has never taken any medication for ME.
https://www.mesupport.co.uk/index.php?page=yoga-my-bed-m-e

 

@Marky
The "specific antibodies" we know of in Cfs, and you can ask Prof. Edwards he will agree with me, are found in many other diseases as side effects.
Sure everyone needs to go find their own way right now to get better with this awful disease, but when 10 different autoimmune treatments dont work, then either you dont do it hard enough, or, the more likely way, it just isnt an autoimmune disease.

Overall response rates were 35.1% in the placebo for the phase 3 Rituximab trail. And to now get excited about a study thats not blinded, when you know this disease can create crazy placebo rates and daily/weekly/monthly severity swings out of nowhere just isnt for me.

Also we talking about one of the worst medicine you would want to take in your life. Something that just kills everything in your body and just slightly favors the immune system with a high chance of creating cancer down the line. You can see that i tried a lot and wasnt scared about taking a lot of things, heck, right now im trying to get SS31 to experiment with it, that said, i wouldnt touch cyclo with a ten foot pole.

 

"The "specific antibodies" we know of in Cfs, and you can ask Prof. Edwards he will agree with me, are found in many other diseases as side effects." That was not my point, i meant that even if we have tested for some antibodies in connection with ME, does not mean we have scratched the surface when it comes to the possibility of ME being autoimmune.

"And to now get excited about a study thats not blinded, when you know this disease can create crazy placebo rates and daily/weekly/monthly severity swings out of nowhere just isnt for me" - It has been my impression that the majority of ME-patients after strict criteria only get "crazy" differences in one direction in functioning level, and thats down. Hence, I get excited when i see people improving on objective markers in treatment studies.

"Also we talking about one of the worst medicine you would want to take in your life." - Thats a quite exaggerated statement imo as its given in lower doses. For sure not a treatment regime u want to take, but for sure not the worst IF it proves to have an effect, considering our extremely low functioning levels.

"You can see that i tried a lot and wasnt scared about taking a lot of things, heck, right now im trying to get SS31 to experiment with it" - I hope u find something that works!