New pilot study in the loop from the researchers at Haukeland

[lansbergen]

I still think that there are people who could be classified as having ME who do not having an antibody mediated autoimmune disease. What I continue to be puzzled about is the most common mechanism for PEM type ME.

Maybe they make the wrong assumption. I noticed flare symptems start 7 to 10 days after reinfection/reactivation . After several days I get an inner drive to do to much and that makes me crash.

Most people will not take notice (or think it is not important) of a mild none productive cough but I learned it was the sighn to be very alert for other symptoms in the animals.

 

[Jonathan Edwards]

@Jonathan Edwards Thank you for your additional information! Is long term remission after a short course of cyclophosmaide a real possibility? Have you seen such cases in other autoimmune diseases, like RA or Lupus? Or do the symptoms almost certainly come back after awhile? I have read, that the drug is used in severe cases of Lupus, MS and RA, especially for a fast symptom control. Why does is work so fast? Does it slow down the whole immune response in addition of killing almost all B Cells?

I guess that cyclophosphamide works quickly by killing other cells that produce inflammatory mediators, like macrophages. It also kills some plasma cells, which would lead to a quicker fall in antibody than killing memory B cells.

Cyclophosphamide can turn the corner for some lupus patients, for instance those with renal disease may get long term benefit in terms of no further renal damage with a course of cyclo. Cyclo can also abort Wegener's granulomatosis or microscopic polyangiitis with long term settling in some cases. However, long term remission is not that common.

 

[melihtas]

I still think that there are people who could be classified as having ME who do not having an antibody mediated autoimmune disease. What I continue to be puzzled about is the most common mechanism for PEM type ME.

If I understand correctly, you think that people having PEM type ME are less likely to benefit from rituximab or cyclophosphamide. That is really bad news for me.

My ME is slow onset. It started about 12 years ago and I only had PEM after heavy anaerobic exercises such as weight lifting. They started after 24-48 hours after exercise and lasted 7 days. Between PEMs, my body and brain were working perfectly fine. Year after year my threshold lowered and I started having PEMs after less anaerobic exercises such as cycling and running. For the last two years I developed orthostatic intolerance and nowadays only sitting for more one hour a day without doing anything causes PEM and turns my life into hell for a week. I am housebound for the last two years and still getting worse. With this progress, I am going to be completely bed-bound soon.

Rituximab study gave us hope and it is an accidental discovery like a lot of other therapies. If it is not going to work for us then we are not even close to getting healthy again because still nobody knows what is wrong with our bodies and we have to wait for another happy accident in medicine.

 

[deleder2k]

If I understand correctly, you think that people having PEM type ME are less likely to benefit from rituximab or cyclophosphamide. That is really bad news for me.

From what I have heard the only "tell" so far is that those who suffer the most from ME are the ones less likely to respond. What could distinguish responders from non-responders could also include b-memory cells in some way.

 

[Jonathan Edwards]

If I understand correctly, you think that people having PEM type ME are less likely to benefit from rituximab or cyclophosphamide. That is really bad news for me.

No, I am just unclear how the mechanisms divide up.

 

[Adele]

What I continue to be puzzled about is the most common mechanism for PEM type ME.

And PEM is one of the biggest symptoms for many of us... It would be so interesting to hear more of your thoughts around this @Jonathan Edwards . Is there a particular reason why just this symptom is so puzzling?

 

[deleder2k]

@Jonathan Edwards, would a blinded study be possible for a dose regime of cyclo that they use in the upcoming open study? It seems to me that side effects are much more common and serious in Cyclo than RTX. If a blinding is major issue, could a possible phase 3 trial consist of the three groups; RTX, RTX+cyclo, and one with only cyclo? I understand it is way to early to speak about this, but it is a pretty interesting idea to speculate about the future.

 

[Jonathan Edwards]

And PEM is one of the biggest symptoms for many of us... It would be so interesting to hear more of your thoughts around this @Jonathan Edwards . Is there a particular reason why just this symptom is so puzzling?

PEM is puzzling in terms of the delay in effect and the long lasting effect. I am not aware that it is a feature of the fatigue of conditions like lupus although this may not be well documented. I am not sure that I have more to add other than is on the 'Do MEs cause CFS' thread.

 

[Jonathan Edwards]

@Jonathan Edwards, would a blinded study be possible for a dose regime of cyclo that they use in the upcoming open study? It seems to me that side effects are much more common and serious in Cyclo than RTX. If a blinding is major issue, could a possible phase 3 trial consist of the three groups; RTX, RTX+cyclo, and one with only cyclo? I understand it is way to early to speak about this, but it is a pretty interesting idea to speculate about the future.

It will be difficult to blind treatment with cyclo because of nausea. So judging the contribution of cyclo to a regimen is going to be difficult. Ritux plus cyclo will feel the same as cyclo maybe but the difference only tells you about the contribution of the ritux.

 

[deleder2k]

Thank you. I see that a treatment regimen that looks like that won't blind either patients or the researchers. Perhaps it could be used to assess the efficacy and safety of the different medicines compared to each other after the phase 3 RTX study is done.
Lack of a biomarker and the fact that it would be an unblinded study would make religious PACE believers, psychosomatics, psychiatrists, Wyller and other go nuts and reject the study because of the placebo effect... If we don't find a biomarker I hope researchers would agree on objective measures like ergo spirometry.

 

[Avena]

I guess one would expect people with thyroid antibodies to be more likely to respond to rituximab than others, although I do not think the Haukeland researchers found any particular association.

I have actually been told that the current Rituximab study excluded patients with thyriod issues? (It might be a false rumour as they have not given any official comment on such details regarding their selection process.)

 

[Avena]

It would only really be worth having it as a standard therapy for severe cases and only if it produced long term remission with a short course, in my view.

I suspect that the sole purpose with this trial is to find something that could help the most severe cases. They had a few non-responders amongst the severe cases in the open Rituximab phase II.

I'm guessing that they are picturing a future with Rituximab for moderate/severe, and Cyclo for the severe/very severe Rituximab-non-responders and/or most acute cases.

 

[DanME]

If I understand correctly, you think that people having PEM type ME are less likely to benefit from rituximab or cyclophosphamide. That is really bad news for me.

My ME is slow onset. It started about 12 years ago and I only had PEM after heavy anaerobic exercises such as weight lifting. They started after 24-48 hours after exercise and lasted 7 days. Between PEMs, my body and brain were working perfectly fine. Year after year my threshold lowered and I started having PEMs after less anaerobic exercises such as cycling and running. For the last two years I developed orthostatic intolerance and nowadays only sitting for more one hour a day without doing anything causes PEM and turns my life into hell for a week. I am housebound for the last two years and still getting worse. With this progress, I am going to be completely bed-bound soon.

Rituximab study gave us hope and it is an accidental discovery like a lot of other therapies. If it is not going to work for us then we are not even close to getting healthy again because still nobody knows what is wrong with our bodies and we have to wait for another happy accident in medicine.

I think, you shouldn't despair. Nobody knows yet, who is likely going to respond and who isn't. As far as I remember, Maria Gjerpe, the founder of the RTX Crowdfunding campaign, had also a more gradual onset, was ill for 23 years and was eventually bed bound, but benefited hugely from RTX. So nothing is written in stone. By the way, most of us have PEM.

 

[Freddy]

@deleder2k
You wrote, that they made a pilot study with 3 patients using Cyclophosphamide , am I right?
Is there a publication concerning the results?

 

[Kati]

@Freddy they are in the very beginning of this study, not sure if the first patients have had the drug yet. completion is expected by 2017

 

[deleder2k]

@deleder2k
You wrote, that they made a pilot study with 3 patients using Cyclophosphamide , am I right?
Is there a publication concerning the results?

I heard so, but I don't think any information about is available online. Not sure if it will be published.

 

[Kati]

@deleder2k really there was a pilot before the 30 patients? do you know anyone who was on the pilot study?

 

[deleder2k]

@deleder2k really there was a pilot before the 30 patients? do you know anyone who was on the pilot study?

Notice that this is a phase 2 trial, it says on the ethics site.

No. I heard that there were 3 patients in a pilot study. I was under the impression that 2/3 almost recovered after a short period of time on cyclo. The other one had a significant effect.

 

[Freddy]

Once again @deleder2k has the information!
"The other one had a significant effect" You mean positive or adverse effect?
Many thanks for answering our questions.

 

[deleder2k]

Positive. I don't know how much better he/she got, but it was considered as a significant effect with respect to overall ME symptoms. I don't know more. I heard it from someone who was at a meeting for the Norwegian ME association in early December. No more information was given.