Rituximab (I'm from Holland)

[Jonathan Edwards]

Again thank you for your sharpness and shining an objective light to this matter. May I ask what COULDN'T be right to this short clip?

I am fairly sure that lung cancer didn't come into it.

 

[Anoirb]

I am fairly sure that lung cancer didn't come into it.

Little rectification: Excuse me they didn't mention lung cancer in the clip indeed.... I must have read it elsewhere

Dr. Edwards another question. May I ask why u discourage trying Rituximab outside trial? Just because of the possible short term results or any other reasons?

 

[Jonathan Edwards]

Little rectification: Excuse me they didn't mention lung cancer in the clip indeed.... I must have read it elsewhere

Dr. Edwards another question. May I ask why u discourage trying Rituximab outside trial? Just because of the possible short term results or any other reasons?

1. Because in the hands of physicians who do not now much about what rituximab does to the immune system it has caused serious harm both in short and long term.
2. Because physicians who do not now much about rituximab still appear to be very happy to use it.
3. Because any physician who has sufficient respect for patients to make sure they treat with rituximab in a responsible way would, to my mind, feel that all such treatments should be recorded and published for the benefit of other patients as part of a trial (i.e. what I did when I started using rituxmab in RA).
4. Dr Fluge and Dr Mella, who have developed the treatment and who therefore consider themselves responsible for its use in ME have indicated that they do not wish physicians to treat patients outside trials.

The problems that arise with non-trial usage are illustrated by the situation in Germany. At least ten patients were treated there but we have no reliable information about them other than that none seem to have improved and one got considerably worse. There are all sorts of possible reasons why but we will probably never know.

 

[Anoirb]

1. Because in the hands of physicians who do not now much about what rituximab does to the immune system it has caused serious harm both in short and long term.
2. Because physicians who do not now much about rituximab still appear to be very happy to use it.
3. Because any physician who has sufficient respect for patients to make sure they treat with rituximab in a responsible way would, to my mind, feel that all such treatments should be recorded and published for the benefit of other patients as part of a trial (i.e. what I did when I started using rituxmab in RA).
4. Dr Fluge and Dr Mella, who have developed the treatment and who therefore consider themselves responsible for its use in ME have indicated that they do not wish physicians to treat patients outside trials.

The problems that arise with non-trial usage are illustrated by the situation in Germany. At least ten patients were treated there but we have no reliable information about them other than that none seem to have improved and one got considerably worse. There are all sorts of possible reasons why but we will probably never know.

Thank you once again. Especially the fact that I've received an email myself from Fluge and Melle with an advice I should not do it outside any trial. I've got one more question sir if I may be tedious.

What's your opinion on OMI (Kogelnik for example) in United States that treats patients with Rituximab?

 

[paul80]

So if the first two phase trials of Fluge and Mella are not considered proof that Rituximab works for M.E, will a successful third trial be enough. If not, what will?

 

[Jonathan Edwards]

Thank you once again. Especially the fact that I've received an email myself from Fluge and Melle with an advice I should not do it outside any trial. I've got one more question sir if I may be tedious.

What's your opinion on OMI (Kogelnik for example) in United States that treats patients with Rituximab?

I do not have any information to go on I am afraid. They have not published anything as far as I know.

 

[Jonathan Edwards]

So if the first two phase trials of Fluge and Mella are not considered proof that Rituximab works for M.E, will a successful third trial be enough. If not, what will?

Dr Fluge would not want to suggest that his trials so far prove rituximab works in ME. The blinded trial did not get a result at its primary endpoint but suggested a result at 6 months. It is promising but no more. The phase 3 study is entirely different in that it is powered to give a clear result, making use of a lot of prior information on what to use as end point. In the middle of next year we should have a pretty definitive answer. There will be further questions about subgroups of responders but the yes or no question should be answered. To obtain approval from government based health systems and insurance providers it may be necessary to confirm the phase 3 findings but the key stage is what is called proof of concept and that in this case will be trial now running.

 

[Hip]

Kolibri mailed me back and they've told me that based on their experience:
That is 1/3 recovers completely, 1/3 makes improvement and 1/3 makes no improvement.

That's very interesting. Out of the 1/3 of ME/CFS patients that recovered completely, did Kolibri give you any indication about how many of these recovered patients needed further rituximab treatment after a year or two, and how many remained permanently recovered after their rituximab treatment?

My understanding is that for rheumatoid arthritis, sometimes rituximab treatment leads to permanent or long term remission from the disease; and sometimes the positive effects of rituximab treatment only last for a year or so, after which the effect wears off, and it is necessarily to give further rituximab treatment, in order to keep the disease symptoms at bay.

 

[paul80]

Dr Fluge would not want to suggest that his trials so far prove rituximab works in ME. The blinded trial did not get a result at its primary endpoint but suggested a result at 6 months. It is promising but no more. The phase 3 study is entirely different in that it is powered to give a clear result, making use of a lot of prior information on what to use as end point. In the middle of next year we should have a pretty definitive answer. There will be further questions about subgroups of responders but the yes or no question should be answered. To obtain approval from government based health systems and insurance providers it may be necessary to confirm the phase 3 findings but the key stage is what is called proof of concept and that in this case will be trial now running.

Thanks for that. If it is successful will it be possible to get it privately in the U.K or does that still require government approval? I think i'm too ill to go abroad even if i could find the money.

 

[Jonathan Edwards]

Thanks for that. If it is successful will it be possible to get it privately in the U.K or does that still require government approval? I think i'm too ill to go abroad even if i could find the money.

I do not know of any physician who understands B cells who would offer rituximab privately in the UK. Treatments of this sort are almost exclusively used in NHS rheumatology and haematology units mostly in university hospitals. If the phase 3 trial is positive I think there is a real chance that one or more university centres in the UK will be persuaded to take on patients. Rituximab was used for rheumatoid arthritis by several centres before it was licensed. Getting approval is complicated but it can be done. With increasing use of rituximab in a variety of diseases private clinics with capable specialists may also take this on, although I do not know exactly who at this stage. I can think of one or two possible names but I do not want to mention specific colleagues without their express permission. When the time comes for physicians to offer treatment privately they should be allowed to make that clear when they are comfortable with it.

 

[paul80]

Sounds hopeful, thanks for the info.

 

[MEPatient345]

@Jonathan Edwards So, you think that Fluge and Mella may release information by mid 2017 about the study being successful or not? I thought the study wasn't due to be published until 2018, so this is wonderful news..

 

[Jonathan Edwards]

@Jonathan Edwards So, you think that Fluge and Mella may release information by mid 2017 about the study being successful or not? I thought the study wasn't due to be published until 2018, so this is wonderful news..

I really do not know but I doubt our colleagues will want to keep totally silent after breaking the codes until a paper is published. If the results are positive researchers will want to be planning further work. Different researchers take different policies on this and we should not hassle our Norwegian colleagues, but my impression is that they will not want to delay progress for reasons of personal kudos or bureaucracy. We can rely on them to let us know as soon as is reasonably appropriate.

 

[deleder2k]

That's very interesting. Out of the 1/3 of ME/CFS patients that recovered completely, did Kolibri give you any indication about how many of these recovered patients needed further rituximab treatment after a year or two, and how many remained permanently recovered after their rituximab treatment?

My understanding is that for rheumatoid arthritis, sometimes rituximab treatment leads to permanent or long term remission from the disease; and sometimes the positive effects of rituximab treatment only last for a year or so, after which the effect wears off, and it is necessarily to give further rituximab treatment, in order to keep the disease symptoms at bay.

I think it is premature to say that 1/3 got "completely recovered". I think their first patient was treated in May 2015. Way too early to conclude whether someone completely recovered. I think they mean that 1/3 have returned to the activity level they had before they got ME. They don't know whether the improvement is permanent yet. From Haukeland's research it looks like we can't expect that.

 

[Hip]

I think it is premature to say that 1/3 got "completely recovered".

I agree, my guess is that by "completely recovered," Kolibri do not mean it is necessarily a permanent recovery, just that the symptoms of ME/CFS have 100% disappeared.

But that is why I wondered if any of their patients needed further rituximab treatment, in which case, these patients would not be permanently cured; but rituximab would be keeping them in remission.

It's possible that rituximab may permanently cure some patients, and for others, they may require further rituximab treatment every year or two to maintain their full remission.

 

[deleder2k]

I wonder the same, but it is too early to say at this moment as their first patient Rituximab did so 1.5 years ago... Hopefully they'll reveal some more information later on

 

[jaybee00]

To Jonathan Edwards...

Regarding this statement...

"Once one has started [tr]eating someone with rituximab there is no way of putting the clock back. The immune system is altered and permanently so, although in most cases it settles back to normal between treatments."

OK, but isn't this alteration desirable? Also, how is this alteration permanent if the B cells come back? And also, trying not to be cynical, or underestimate the need for specific expertise or patient monitoring, etc., but there are likely many treatments administered by many physicians, who don't understand the mechanisms behind the medications/treatments that they prescribe...they simply prescribe/treat based on the fact that it works.....

Thank you for your contribution to this forum.

 

[JES]

To Jonathan Edwards...

Regarding this statement...

"Once one has started [tr]eating someone with rituximab there is no way of putting the clock back. The immune system is altered and permanently so, although in most cases it settles back to normal between treatments."

OK, but isn't this alteration desirable? Also, how is this alteration permanent if the B cells come back? And also, trying not to be cynical, or underestimate the need for specific expertise or patient monitoring, etc., but there are likely many treatments administered by many physicians, who don't understand the mechanisms behind the medications/treatments that they prescribe...they simply prescribe/treat based on the fact that it works.....

Thank you for your contribution to this forum.

How I read it is that he means that the alteration is "permanent" in the sense that it cannot quickly be undone, you are stuck with less or no B cells for a longer period of time following the initial treatment. Whereas normally if you take a medication you can typically expect its effects to wear off in a matter of days, so if you had an unpleasant reaction it's as simple as stopping the medication, whereas with rituximab if something goes wrong there is no way to undo the effect.

 

[frederic83]

Do we know why it takes weeks before Rituximab has any effects ?

 

[JES]

Do we know why it takes weeks before Rituximab has any effects ?

If I remember correctly, the theory was that once you kill off the B cells with Rituximab, you still have high levels of various circulating auto-antibodies or whatever substance in the blood that is wreaking havoc with the mitochondria and immune system. Once you get rid of the B cells, the manufacturing of these auto-antibodies stops, but it will take a while before all the old auto-antibodies will clear off. Hence the delay.