Astounding Norwegian research breakthrough with Rituximab can solve CFS mystery!!!

[Sasha]

eg: The saline placebo would have had no affect. Maybe the Rituximab gave a bit of a 'buzz', and that led to patients tending to be more positive in reports of their symptoms?

This is a good point and one that is applicable to all trials using placebos with double-blinding in which the active drug has distinctive side effects - there are cues that patients might be able to use to determine that they're on the active medication even with the blinding. Researchers are aware of it and it's hard to get around. Like a lot of these things, it's less likely as the explanation for the result of the trial if the difference between active drug and placebo groups is big. I think that in the case of this trial, the late-arriving improvement is also an argument against patients simply getting a bigger placebo/perceived improvement boost from Rituximab - I'd expect those effects to kick in pretty quickly.

Personally, I've always been surprised that researchers are not required as standard in every trial to ask patients whether they think they have been administered the active drug or placebo. At least they'd then have a measure of patients' ability to tell which condition they're in, despite the attempts at blinding.

 

[Sasha]

Actually, the age of the drug could be a small problem at first, since the patent on Rituximab expires next year, Roche has reportedly shown no interest in sponsoring studies of its use for ME/CFS (a rational decision in a for-profit venture, they would get little return if generics come out next year). And they have known about this possibility since at least 2009 when the first success was reported... I think it probably was strategic for them to ignore this though, not due to any disbelief or problem with ME/CFS.

In an interview, the study authors said: "The treatment is relatively expensive so far (20 to 25,000 [Norwegian krone] per infusion), but the price is expected to fall because the patent to the pharmaceutical company goes out within a couple of years. Moreover, a number of pharmaceutical companies that have new drugs with similar mechanism of action [in the pipeline].

So I wonder if those companies might have an interest in doing trials? Perhaps with safer drugs than Rituximab? I agree there's an issue of getting money for the next phase of Rituximab studies but Fluge and Mella are already working on their next. Also, if treatment costs with Rituximab go down and if it's a relatively short course of treatment for ME patients (as maybe suggested by some patients making good recovery on only two doses), governments could expect a good return on their money for treating patients and getting them off benefits and back to work paying taxes. If I were writing a research proposal for a government funding body, I'd be making exactly that argument.

 

[Snow Leopard]

In the paper (p. 8) the authors say that they retrospectively applied the CCC (they'd used the Fukuda 1994 criteria to select patients) and one of the two placebo responders didn't fit the CCC. They don't say (can't see it now, anyway!) whether that was the one who had been the big responder.

Actually, they did.

Retrospectively, we checked the 30 patients according to the Clinical Working Case Definition (Canadian criteria) [8]. Two patients in the placebo group did not fulfil these criteria, and it could therefore be argued that they might not have CFS. One of these had almost no pain, and one had only slight cognitive symptoms and also reported marked mood disturbances. The latter patient reported major improvement after intervention with saline and was recorded as one of the two responders in the Placebo group.

It's really difficult to measure disability and improvements with CFS, and that can end up sending us down dead ends.

I wish studies would start to use objective activity measures as secondary outcomes at the very least.

 

[snowathlete]

I didnt know that the patent was about to expire, but whereas this brings some negatives, such as you mentioned, it also brings about some plus points.

If nothing else, it should mean that the drug becomes cheaper, and that probably helps the case for NICE in the UK agreeing to its prescription on the NHS.

Other groups will sponsor the studies. In fact i spotted online last night that a group has already said they are interested in sponsoring a study in the UK and they are inviting labs to approach them regarding this.

Of course, the more we can do to shout about this and get research funding, forward momentum - the better.

Your right of course that this doesnt explain what is wrong with our B cells, but as you point out Kurt, we now have a better idea of where the problem is.

Hopefully this will be the first treatment, and others will follow later that are more targetted on the root cause, but in the meantime, hopefully we can get some normality back to our lives in the shorter term, thanks to this drug.

Regarding applying pressure - has anyone drafted a letter yet, that we can all use as a template to send to our MPs?

 

[redo]

Joel,
Actually, the age of the drug could be a small problem at first, since the patent on Rituximab expires next year, Roche has reportedly shown no interest in sponsoring studies of its use for ME/CFS (a rational decision in a for-profit venture, they would get little return if generics come out next year). And they have known about this possibility since at least 2009 when the first success was reported... I think it probably was strategic for them to ignore this though, not due to any disbelief or problem with ME/CFS.

I've understood it such that the patent expires in 2015. http://neuroimmunology.wordpress.co...ful-story-of-rituximab-in-multiple-sclerosis/
If you have a source saying 2012, than that's great news!

 

[Sasha]

Other groups will sponsor the studies. In fact i spotted online last night that a group has already said they are interested in sponsoring a study in the UK and they are inviting labs to approach them regarding this.

Hi snowathlete - I saw that statement on the ME Association's website, which is great. I hope UK researchers are interested.

 

[LazyLizard]

Here's my outlook for the CFS/ME future:
Within 2-3 months research teams will jump on Rituximab, run bigger studies to confirm the effectiveness of the drug and how to prevent relapses. It will also point us towards the safest way to deal with possible side effects so we won't have to worry about that.
Then within the year the patent of Rituximab expires and we can all go on the generic version at, say $39.95 a pop, at your friendly
local tranfusion centre.
Another 3 months pass and we'll all be back in full-time employment, enjoying our lives and bungee jumping and so forth.
At the same time explanations for the mechanics of the drugs success in ME/CFS will be forthcoming and lead to even better
treatment.
And then, with our new found energy, stamina and pain free we'll drag Wesseley in front of the International Human Rights Tribunal
for crimes against humanity.

Go Norway :victory:

p.s.: I am not trying to be sarcastic. Just happy that there are medics out there, not blinded by PACE, take us seriously.
The way XMRV went and the PACE thing was a bit havy lately.

 

[GaryK]

Rituximab and Regulator B cells

I just wanted to add this tid bit to the discussion here of great news but go cautious plz!

A year ago I was studying some new research with MS and other Auto Immune disorders. They were talking about newly discoverd regulatory B cells (that tell T cells what to do). "Now it seems that T-cells are not the immune system's only regulators. Experiments suggest that under some circumstances, B regs regulate T-cells, providing a shadow role for B cells.
"Diseases we've traditionally thought to be mediated by T-cells might actually be regulated by B cells," says Kevan Herold of Columbia University in New York. Boosting B regs might therefore provide new opportunities for treating autoimmune diseases, while inhibiting B regs it could be a new way to treat cancer."

They found when using Rituximab Chemo to rid the body of ALL B cells that in short time the B cells that came back were B reg10 cells ONLY "These are major regulators of the immune system in allergic disease," Fallon concludes. B regs seemed to work by releasing a chemical called IL-10 into the lungs, drawing in regulatory T- cells (T regs), which in turn inhibited immune attacks.
IL-10 played a similar role in a subset of B regs, which Thomas Tedder at Duke University School of Medicine in Durham, North Carolina, calls B10 cells. (the kind they thought responsable for intsructing T cells to kill cancer which kills B cells). "First prescribed for the treatment of B cell lymphoma, a type of cancer, the drug has also reduced symptoms in people with diabetes, MS and rheumatoid arthritis. Rituximab most likely knocked out all the B cells to start with, and then, for some reason only the B regs grew back, which helped suppress autoimmunity, suggests Frances Lund of the University of Rochester Medical Center in New York (Nature Reviews Immunology, DOI: 10.1038/nri2729)."

"In individuals with cancer, however, it might be desirable to suppress B regs. Preliminary evidence suggests that as well as keeping autoimmunity in check, B regs also help dampen the immune system's natural ability to recognise and destroy tumours.
Tedder's team has already created antibodies that can deplete B10 cells - but not other B cells - in mice, and says he has similar antibodies that may selectively deplete human B10 cells - although he hasn't yet tested them in people.
Arya Biragyn of the US National Institute of Aging, and his colleagues, also announced at the Baltimore meeting that they have identified a separate set of B regs that cancer seems to recruit in order to avoid detection by the immune system. Destroying these cells might make let's hope you have deep pockets cancer immunotherapies work better.
"Even if you transiently wipe out B cells during immunotherapy, this should give you very potent anti-tumour responses against hidden tumour cells, Biragyn says."

Also Corts write up on from page mentions Dr. Peterson and the use of Rituxamib and the differing B cell types? ( I need to read that part again as I think this is Key to what they need to research for us here and other auto immune disorders.)

 

[max]

And then, with our new found energy, stamina and pain free we'll drag Wessely in front of the International Human Rights Tribunal for crimes against humanity.


I like your vision of the future - very much - (as an activist)


:victory: GO NORWAY :victory:

 

[Kati]

One thing to keep in mnd is that Rituximab is only one of many drugs of it's class called "monoclonal antibodies". As Dr Fluge and Mella mentioned in the Invest In Me conference, there might be other drugs in the pipeline that could be applicalbe for our disease. I hope that the success of this drug on our disease will get big pharma and rheumatologist excited. it could be a bramd new niche for them- let's just hope they define the niche properly.

 

[SilverbladeTE]

Here's my outlook for the CFS/ME future:
Within 2-3 months research teams will jump on Rituximab, run bigger studies to confirm the effectiveness of the drug and how to prevent relapses. It will also point us towards the safest way to deal with possible side effects so we won't have to worry about that.
Then within the year the patent of Rituximab expires and we can all go on the generic version at, say $39.95 a pop, at your friendly
local tranfusion centre.
Another 3 months pass and we'll all be back in full-time employment, enjoying our lives and bungee jumping and so forth.
At the same time explanations for the mechanics of the drugs success in ME/CFS will be forthcoming and lead to even better
treatment.
And then, with our new found energy, stamina and pain free we'll drag Wesseley in front of the International Human Rights Tribunal
for crimes against humanity.

Go Norway :victory:

p.s.: I am not trying to be sarcastic. Just happy that there are medics out there, not blinded by PACE, take us seriously.
The way XMRV went and the PACE thing was a bit havy lately.

Agreed!
gawd DAMN do I want to see that grinning...person...in The Hague or Old Bailey! Along with lots of other...persons.
*avoids using nasty names of truly sulforous vitriol, lol*


one thing though: those of us who've had this for a long time, like it or not, even if a treatment is found will probably have suffered long term damage and debility, so folk do need to be aware of that, and hence WHY THE FLAMING HELL those SOBs who prevented treatment or biological research, and very conflicting links with government, welfare systems, insurance companies etc are *CRIMINALS*, not merely "researchers who got it wrong".
having such a nasty disease for long periods inevitably causes harm , one way or another
sorry, just being realistic

I hope one day to be free of this horrible illness, but I don't expect to recover my once excellent health 'cause it's been 17 FRIGGIN YEARS thanks to that ONE ASSHOLE and his sympaticos diablos
Sigh
what's worse really is not the Weasels, it's really the way they were let free to do their evil by a bigotted, backward, mysognistic, corrupt, bloated, Victorian, compassionless, rotten bloody system, mostly the medical world which seems ot have sod all understanding of science and common sense.

All it takes for evil to flourish, is for good men to do nothing

So, where were you, phsyicians, healers of the sick, guardians of the weak and holders of the oath of Hipporates and the Rod of Asclepius, hm?
Where the hell was your common sense, reason, udnerstanding of science and respect for patients?

 

[max]

Any media yet?

 

[redo]

About the 7% of placebo taker responding, that's great figures.

Here's some data on another monoclonal antibody used for RA and UC. UC figures:
" [...] infliximab in ulcerative colitis and showed that 44-45% of patients treated with infliximab for a year maintained a response to the medication, compared with 21% of patients who were treated with placebo medication. At 2 months, the response was 61-69% for patients treated with infliximab, and 31% for those who were treated with placebo"

We're looking at 2/15 (or 1 if you leave out moderate response).

Here's a quote from cancer.org about placebo in general.

Even though placebos do not act on the disease, they seem to have an effect in about 1 out of 3 patients.

 

[alex3619]

Hi, I am very sceptical of any placebo response in an illness that has a variable course and is frequently misdiagnosed. One or two positive placebo responses does not make it the placebo response. Most of the well established improvements from placebo involve pain, not pathology. A placebo can change the attitude towards pain, which makes it better tolerated. In short, I am yet to be convinced a low placebo rate has any significance - its as good as zero. However this was a tiny study. It will be interesting to see the results in a larger study when it comes out. Personally I suspect that the real surprise in this study is yet more evidence indicative of the possibility that Fukuda CFS is two different diseases, or more; either that or misdiagnosis is even more common under Fukuda than I thought. This might also be true of ME definitions. Now the researchers are justified in saying that the non-responders might just need more prolonged treatment - look at how some of us respond to antivirals. So this is going to be some very very interesting research. Bye, Alex

 

[Andrew]

Assuming we find this same reaction in lots of patients, it's possible that this will need to be pulsed. Turning off the B cells all the time could cause problems as well.

 

[gu3vara]

To me it's just a proof of concept, I'd like to know the effect of this treatment on their cell-mediated immune system. Will the NK cell function improve after killing those B cells? Shutting down the humoral immune system while having troubles with the cell-mediated part sounds like an awful idea. I can't see anything healthy coming out from taking this drug.

It's interesting though cause it finally proves the immune nature of the disease to the world and might lead to other discoveries.

 

[RUkiddingME]

I totally agree Helene: Canada is not the place to be when you are sick. I have a two year wait time to see a doctor for CFS. A two to three year wait time for a tilt table test and the list goes on!!! I have had to to to the States for help but now can no longer afford to go. For Canada to go ahead and get a study going or approve this new med for us is hightly unlikely.

 

[Boule de feu]

Here's my outlook for the CFS/ME future:
Within 2-3 months research teams will jump on Rituximab, run bigger studies to confirm the effectiveness of the drug and how to prevent relapses. It will also point us towards the safest way to deal with possible side effects so we won't have to worry about that.
Then within the year the patent of Rituximab expires and we can all go on the generic version at, say $39.95 a pop, at your friendly
local tranfusion centre.
Another 3 months pass and we'll all be back in full-time employment, enjoying our lives and bungee jumping and so forth.
At the same time explanations for the mechanics of the drugs success in ME/CFS will be forthcoming and lead to even better
treatment.
And then, with our new found energy, stamina and pain free we'll drag Wesseley in front of the International Human Rights Tribunal
for crimes against humanity.

Go Norway :victory:

p.s.: I am not trying to be sarcastic. Just happy that there are medics out there, not blinded by PACE, take us seriously.
The way XMRV went and the PACE thing was a bit havy lately.

LOL a very nice outlook, indeed.
I say yes to everything you have written, except for the bungee jumping.
I'm not a big fan. LOL

 

[Snow Leopard]

Hi, I am very sceptical of any placebo response in an illness that has a variable course and is frequently misdiagnosed.

Good point. That's why we shouldn't call double blind RCTs "placebo controlled" as we are controlling for more than just the placebo effect.

 

[kurt]

I've understood it such that the patent expires in 2015. http://neuroimmunology.wordpress.co...ful-story-of-rituximab-in-multiple-sclerosis/
If you have a source saying 2012, than that's great news!

Good point, my source was the German pub Spiegel, they may have been talking about an EU patent. There are several patents usually in meds like this, the European patents, the US patents, other international, etc. Also there are usually spin-off drugs, various brands, that tweak the formulas and get new patents. So maybe all the dates are correct, depends on which patent you refer to. This page says one patent expires 2013, maybe that was what Spiegel was referring to:

http://www.pharmatimes.com/article/11-01-06/Spectrum_plans_to_develop_biosimilar_Rituxan.aspx

Also, looks like the US patent is 2015 and maybe 2018, but there is a firm developing bio-identical product already so there will eventually be generics. Just may take a few years before alternative drugs are available. (sorry for raising hopes of 2012!! should have gotten more sources before posting that)

Which brings up a point, technically I don't think a mono-clonal antibody is a drug. Although probably classified as such, but it is an artificial or engineered biologic, or something like that.