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

[sensing progress]

Hi Tia, I haven't heard about any american scientists getting the same results, could you provide a link or source? I would be very excited to read it. I haven't read this entire thread so my apologies if it has been mentioned before.

See here: http://bikechick06.blogspot.com/2012/01/visit-at-dr-kogelniks-office.html

 

[alex3619]

Rituximab is available NOW. However it has to be used off-label by a doctor who either is exempt from misconduct charges or willing to risk them ... and you have to pay cash, including all secondary and follow up expenses. No insurance will cover it, not even government. Furthermore we have little idea as to how to identify non-responders from responders. We also don't have an optimum protocol. All these problems will mean that very very few will get treated under the current conditions.

Now once a phase 3 clinical trial is done, that changes. We have a protocol. We have evidence that it works. We have evidence of sufficient quality that we can demand insurance covers it, demand governments make it available or subsidize it. It becomes available to everyone likely to benefit from it ... but to make that happen faster is political.

Ampligen works. Ampligen was discovered to work around 1988. We are still waiting.

So my best case is two years before everyone can get it. My worst case is twenty-five, but that could be an optimistic worst case. This of course presumes that the phase 3 trials show it works and works well - its not done till the science is done.

Bye, Alex

PS If phase 3 clinical trials start this year, expect a two to three year delay before they are completed. Phase 3 trials are long and complicated .... not done in a night and day. For one thing you have to track patients on treatment over time.

 

[SOC]

One thing the Ampligen story suggested to me is that we need to make it clear not only that the medication has an effect, but also that the illness is serious enough to justify small improvements or risking potential side effects. My feeling is that if the Ampligen proposal to the FDA showed the kind of results it did for, say, cancer or HIV, Ampligen would be on the market for it today. There was something funny in the wording of the FDA denial which I can't recall well now, but I seem to remember as sounding something like "results not worth the side effects"....?

We have to make sure, if we want Rituximab approved for ME, that the bureaucrats making the decisions understand the magnitude of disability associated with ME. Otherwise some ding-dongs are going to claim that the side effects of B cell depletion are hardly worth making people a little less fatigued.

Awareness in medical bureaucratic circles is better than it was pre-XMRV. Still, we have a long way to go.

 

[Snow Leopard]

Basically what it will take is a socialised system to approve the drug first and the rest shall follow. The economic costs of CFS are large and similar to severe RA etc, and the drug is approved for that condition, so...

 

[Tia]

Rituximab is available NOW. However it has to be used off-label by a doctor who either is exempt from misconduct charges or willing to risk them ... and you have to pay cash, including all secondary and follow up expenses. No insurance will cover it, not even government. Furthermore we have little idea as to how to identify non-responders from responders. We also don't have an optimum protocol. All these problems will mean that very very few will get treated under the current conditions.

Now once a phase 3 clinical trial is done, that changes. We have a protocol. We have evidence that it works. We have evidence of sufficient quality that we can demand insurance covers it, demand governments make it available or subsidize it. It becomes available to everyone likely to benefit from it ... but to make that happen faster is political.

Ampligen works. Ampligen was discovered to work around 1988. We are still waiting.

So my best case is two years before everyone can get it. My worst case is twenty-five, but that could be an optimistic worst case. This of course presumes that the phase 3 trials show it works and works well - its not done till the science is done.

Bye, Alex

PS If phase 3 clinical trials start this year, expect a two to three year delay before they are completed. Phase 3 trials are long and complicated .... not done in a night and day. For one thing you have to track patients on treatment over time.

How can they see that?

 

[alex3619]

Hi Tia, they are investigating responders vs. non-responders. Essentially, they are looking for a biomarker. If they find one we can be screened and know to a reasonable certainty before we are treated that it will work, or know it probably wont and the risks and cost are not worth it. We NEED that biomarker.

SOC, Ampligen is a special case I think, I use it to show how hard it can be once politics is involved. CFS was touted as psychosomatic, Ergo no need for an antiviral strategy. EBV was "disproved" as a cause, so Ergo no need for Ampligen. Ampligen was a class of drug all to itself, until recently there were no similar drugs. Ergo the FDA has no experience with these drugs, best to be cautious - Ergo delay the approval, demand more data.

I wish Ergo would take a holiday.

It only takes a few in the FDA to think like I suggested to hold things up. Just a few individuals in key positions.

I hope Rituximab is different. For one thing if its approved in Europe, the FDA is going to be under enormous scrutiny if they decline to approve it for ME.

Bye, Alex

 

[Tia]

Hmm, as far as I know, it shouldn't be a problem to get Rituximab (Or rituxan as it's also called) here in Sweden at least. I thought the biomarker was only an extra add so they could test people in the future and see if they have it and not have to go trough a bunch of other expensive tests to rule out other disorders?

I'm telling ya..if they don't get us a friggin cure soon, I won't last much longer..

 

[alex3619]

Hi Tia, there are many reasons to develop biomarkers. One is for diagnosis. Another is for determining if someone will respond to drug therapy. These are different.

The survival rate for those who have been as sick as long as I have is probably dismal. We needed a cure decades ago.

Bye, Alex

 

[Snow Leopard]

I thought the biomarker was only an extra add so they could test people in the future and see if they have it and not have to go trough a bunch of other expensive tests to rule out other disorders?

There is definitely truth in that. But because of the contested nature of CFS, a biomarker also brings social legitimacy and would make make the prescription of slightly risky drugs like Rituximab more acceptable to (close minded) doctors.

 

[Tia]

There is definitely truth in that. But because of the contested nature of CFS, a biomarker also brings social legitimacy and would make make the prescription of slightly risky drugs like Rituximab more acceptable to (close minded) doctors.

Oh, yeah, yeah, yeah yeah! (Nodding) That to. Like a test for HIV, huhu. Either u have it, or you don't. well, it'll sure save money for the healthcare when it comes.

 

[SOC]

SOC, Ampligen is a special case I think, I use it to show how hard it can be once politics is involved. CFS was touted as psychosomatic, Ergo no need for an antiviral strategy. EBV was "disproved" as a cause, so Ergo no need for Ampligen. Ampligen was a class of drug all to itself, until recently there were no similar drugs. Ergo the FDA has no experience with these drugs, best to be cautious - Ergo delay the approval, demand more data.

I wish Ergo would take a holiday.

It only takes a few in the FDA to think like I suggested to hold things up. Just a few individuals in key positions.

I hope Rituximab is different. For one thing if its approved in Europe, the FDA is going to be under enormous scrutiny if they decline to approve it for ME.

Bye, Alex

All so true. I, too, hope Rituximab is different. The fact that it is currently in use for other conditions, especially non-fatal ones like RA should be a big help to us. Perhaps the political battle will not be quite so overwhelming as it is for Ampligen.

I've got a couple of bucks to chip in to send Ergo on a holiday.

 

[oceanblue]

True Size of the Rituximab Effect

I recently posted a blog on how the SF-36 scores buried deep in the paper give a better indication of the peak effects of Rituximab than the primary outcome measure of fatigue scores. I hope the blog is a little more comprehensible than my original post on the subject.

 

[biophile]

SOC wrote: ... the illness is serious enough to justify small improvements or risking potential side effects.

True and agreed, but I can imagine Wessely et al making the exact same argument about CBT/GET. Personally I would be hesitant over the potential side effects of treatments like Rituximab because a number of substances which were supposed to be relatively safe have apparently worsened my health and right now I couldn't tolerate another permanent backwards slide and want to keep whatever limited functionality I have left. It all makes for some difficult decisions, the illness is also serious enough to be scared about losing even more functionality. I have a similar issue with the hypothetical scenario of being diagnosed with some form of cancer, I'd rather die or risk death than be treated with standard chemotherapy in my current condition.

 

[ramakentesh]

Fascinating. If I could speculate, might it be because the body only have around 5 liters of blood (blood containing waaay to high levels of cytokines and other immune parameters), and when you "water it down", you feel better for a while...? Just some thoughts (not facts . It would fit with the hypothesis that our symptoms are mostly autoimmune in origin (without stating anything about what/which infection is causing the auto immunity).

Possible, but it is more likely the volume deficit relates to low renin, high angiontesin II or increased dopamine salt extraction ater orthostatic stress.

 

[ramakentesh]

Moderator: Personal attack removed.

I would also like to urge those people framing this drug as some kind of miracle cure to administer themselves a strong dose of scientific scepticism and cautiousness, the worst thing that could happen is a repeat of the XMRV drama. At the moment these results tell us nothing concrete about the underlying pathology, absolutely nothing - they took very detailed measurements of immune parameters and yet no trend emerged, that should be a strong warning sign that we are barely scratching the surface.

I dont believe your scepticism is warranted. however it should have been with XMRV which as far as I could tell was always too good to be true (that the first retro virus looked for happened to be in nearly all CFS patients tested). I remember people distinctly saying 'When i test positive to XMRV and I know I will' - sounds more like faith than science to me.

However, in relation to an autoimmune hypothesis there are a number of supporting points - although these are obviously conjectural:

1. waxing and waning presentation is common in CFS and in nearly all autoimmune illnesses.
2. female to male ratio - identical to most but not all autoimmune diseases.
3. higher prevalance of autoimmune comorbidity in CFS patients.
4. precipitating event - infection, stress or pregnancy as in most autoimmune disorders.
5. higher prevalance among CFS patients of first degree relatives with autoimmune disorders.
6. reports of improvement on TNF alpha inhibators for a small group of patients with CFS.
7. apparent higher prevalance of certain histocompatibility in CFS patients (HLA-B27 as an example certainly in POTS).

And the clincher is that most CFS patients dont measurably decline. While they may progress in reported symptoms, measurably their bodily systems do not demonstrate signs of progression. Any long term infection would have progressive consequences. I can think of no examples where long term infection does not.

from my own perspective I developed CFS/POTS when I developed ankylosing spondylitis and I noticed on AS forums that if I took away the inflammatory pain, the fatigue, cognitive problems and many of the other symptoms I experienced were identical in both CFS and AS forums. Which I thought was interesting.

I dont feel that the success of this medication in some patients tells us NOTHING about CFS - it tells us something. We cant however I agree jump to conclusions about what it tells us.

One thing I do know is that it is unlikely that we will work it out ourselves from the comfort of our own living rooms...

 

[ramakentesh]

I hope that this medication at least opens up a new direction in CFS research as the autoimmune hypothesis has received far too little interest from research in the past, despite its obvious attraction.
And ofcourse funding for autoimmune disorders is quite large.

There are a myriad of potential autoimmune mediated targets: Net protein, beta 1/2 adrenoreceptors, ang II receptors are promising targets for a start - none of which have received any research thus far. Antibodies can be quite hard to detect. In the old days they would just squirt the blood of a patient into a poor rabbit to see if it came down with the same condition. Archaic but at one time was viewed as conclusive.

The theory regarding innate immune system activiation in some auto inflammatory disorders may well be that the immune system in these patients is faulty due to their histocompatibility. As an example they believe in Chrohns that the innate immune system is unable to deal with certain pathogens so just starts attacking the whole area. the analogy is like a machine gun - if you can shoot the man you just spray the hole area.

So potentially rather than overactive immune systems, the new direction they are looking at is ineffectual ones.

There is also the often mentioned molecular mimicry theory - that certain bacteria give off proteins that confuse the body into attacking areas with similar histocompatibility.

 

[SOC]

True and agreed, but I can imagine Wessely et al making the exact same argument about CBT/GET. Personally I would be hesitant over the potential side effects of treatments like Rituximab because a number of substances which were supposed to be relatively safe have apparently worsened my health and right now I couldn't tolerate another permanent backwards slide and want to keep whatever limited functionality I have left. It all makes for some difficult decisions, the illness is also serious enough to be scared about losing even more functionality. I have a similar issue with the hypothetical scenario of being diagnosed with some form of cancer, I'd rather die or risk death than be treated with standard chemotherapy in my current condition.

Our differences in outlook may come from differences of experience with the medical world. Beyond that, we are agreed.

My personal position is that I want reasonable choices. I don't want those choices completely decided for me. Cancer patients have the choice of no treatment, and in some cases moderate and highly toxic choices. They are not forced to take dangerous treatments, but they have to option to educate themselves and make the best possible decision for themselves.

We don't have options. Some of us are essentially forced into low-effect, high-risk treatments like CBT and GET. Inexcusable, imo. My vision is: give me some available treatments, outline the risks, let ME do my research and let ME decide.

 

[usedtobeperkytina]

Another

Another reason for a biomarker is that the FDA wants an objective measure that the improvement from a drug is affecting the biological abnormality, not just the subjective patient-reported symptoms.

You may also note that Hemespherix is also spending their money looking for a biomarker, same reason.

By the way, sometimes, things happen backwards. In fact, it is often the case in medical science.

The way you find out about the disease is to stumble into something that makes it better. This is the clue that then leads to understanding the pathophysiology.

Most think it is always look for the abnormalities, then find a treatment. Sometimes the treatment that works tells you what the abnormality is.

Tina

 

[Tia]

Well, I for one want to push for autoimmune diseases, since I only this summer found out I have one. So I have it on black and white and I've heard many others have the same thing here..?

 

[Kate_UK]

Fluge and Mella will speak at the London Invest in ME conference on June 1st 2012.

http://www.investinme.org/IiME Conference 2012/IIMEC7 Agenda.htm