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Rituximab and ME/CFS in the UK - MEA update

Kati

Patient in training
Messages
5,497
Here in Canada I have the choice between group therapy and going out of country for treatments. Which one do I pick? The choice is simple. I do not need group therapy, nor do I need to learn relaxation techniques, or how to exercise myself back to health.

These folks at the clinic while they may mean well, have no clue about what I need. I need treatments. I need my health care systems to give a shit about what is going on in my body and to give access to testing and treatment. This is called practicing medicine.
 

Aurator

Senior Member
Messages
625
Remember, here in the UK, the licensing authorities and NICE will want to see robust evidence of both efficacy and safety in ME/CFS in several large and high quality independent clinical trials before this drug is approved for use in ME/CFS
I'm fully behind the idea that efficacy and safety need to be firmly established before Rituximab is approved for use in ME/CFS.

The only snag is that, however compelling the evidence becomes that Rituximab is safe and effective, NICE can and probably will assert that the evidence is still insufficient. I doubt whether anyone on the forum is naïve enough to believe that the NICE hierarchy are committed to the idea of funding a high-cost biomedical treatment for a condition that the majority of them almost certainly still choose to regard as psychosomatic. I predict that if ever NICE do give their consent to the use of Rituximab it will only be after a monumental battle that they, against all the odds, have lost.
 
Messages
13,774
There was at least one positive anecdotal response to rituximab on here.

I'm pretty wary of using anecdotal reports for anything, but when the Norway trial should be reporting soon, I can see why hearing less than positive anecdotal responses could encourage people to wait before setting up a UK trial. Even if the Norway trial is positive it could well be that a smaller sub-group than expected benefit, and that particular care needs to be taken with patient selection, especially for a smaller trial.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
We know that not everyone will respond to Rituximab, so I'm not sure why it's newsworthy that there have been anecdotal reports of non-responders. Perhaps less than half of the community will respond? Perhaps those who have sought treatment are long-term patients which has biased the results? The whole point in clinical trials is that anecdotal reports are interesting, and can be a starting point, but they tell us little about the potential of a treatment.
 

Kati

Patient in training
Messages
5,497
We know that not everyone will respond to Rituximab, so I'm not sure why it's newsworthy that there have been anecdotal reports of non-responders. Perhaps less than half of the community will respond? Perhaps those who have sought treatment are long-term patients which has biased the results? The whole point in clinical trials is that anecdotal reports are interesting, and can be a starting point, but they tell us little about the potential of a treatment.
Only about 30% responds to Rituximab for rheumatoid arthritis. It would not deter me from getting a chance at getting better.
 

charles shepherd

Senior Member
Messages
2,239
If the anecdotal information is simply the little that is already in the public domain; a few apparent patients with me/cfs who have had rituxan without it working in the US, conducted by one group, then I am not sure I agree that it should be taken into consideration when deciding when, where and if to conduct a formal trial in the UK.

If the information was more compelling then I could perhaps agree with that view a bit more, but it seems very weak reasoning to me. I mean, we had six? patients in the original positive pilot study in Norway and that was rightly considered too small to draw any conclusions from and that was a formal trial. So even if we had a similar number in the US who reported the opposite in a trial that again would not be sufficient to draw any conclusions, it would at best create caution and uncertainty as it conflicts with reports from Norway...but we aren't even talking about that. We're talking - so far as I know - about a few patients outside of a trial, who had the drug given by the same group in the US and told people on the net that it didn't work for them. It's really no evidence at all, in my opinion.

Given patients are in need of a treatment, there is some formal evidence to suggest rituxan *might* work, and that proper formal trials take time to conduct, before which any potential treatment will not be possible in the UK, I'm disappointed at how long it is taking to get going. I know it isn't easy, it has to be done properly, and there are a lot of obstacles to overcome, but that just makes it more annoying that such weak evidence being discussed is causing serious questions as to when and if a trial should be conducted in the UK.


When a doctor becomes aware of this type of fairly consistent anecdotal evidence - either directly from the person involved or as 'patient evidence' posted on a forum such as this - in connection with the use of something like rituximab, they also need to be talking to the doctors who have been prescribing rituximab outside a clinic trial

To me this is just comon sense

As I have repeatedly said in previous discussions about the importance of 'patient evidence' in ME/CFS - doctors do need to listen to what their patients are telling them about the safety and efficacy of both drug and behavioural interventions

We all know what happens here in the UK when doctors rely on the evidence in favour of using CBT and GET in everyone with mild or moderate ME/CFS based on what was found in clinical trials and ignore the very differing patient evidence that the MEA collects on an on-going basis
 

Research 1st

Severe ME, POTS & MCAS.
Messages
768
Here in Canada I have the choice between group therapy and going out of country for treatments. Which one do I pick? The choice is simple. I do not need group therapy, nor do I need to learn relaxation techniques, or how to exercise myself back to health.

These folks at the clinic while they may mean well, have no clue about what I need. I need treatments. I need my health care systems to give a shit about what is going on in my body and to give access to testing and treatment. This is called practicing medicine.

Very well worded. Patient choice 1st, Politics 2nd etc, but that's how ethically minded people think with a brain!

The UK's obvious caution over changing the old boy network ownership of CFS/ME as a mind-body illness into an Autoimmune Disease, is a big problem because of the history they have to this day. One of backing disease denial, as evidence based medicine. (CBT to change alleged beliefs in untreated disease + GET to prove, the patient can do more and isn't actually biologically disabled after all). That's the cognitive behavioral approach to CFS claimed to be harmless, always known to be useless.

Using sequential logic does not apply to the use of Rituxumab in UK for the state, so all we get is silence and no action. Putting alleged 'Functional Somatizers' on immune therapy goes against the NHS communist regime's ideal of 'cost effective'. It also risks embarrassing the state, if even 10% of people respond, because these people will sue for damages, having being told they were mentally deficient and handed a therapy (CBT/GET) which failed in the PACE trial even for those with F48.0 Chronic Fatigue only :nervous: - Hence no PACE trial raw data and no paper retraction will ever happen, it cannot do politically. Politics created CFS after all, not Science.

Instead, blaming patients with neuroimmune disease is much more cost effective for any Government. CFS patients then can be denied all funding for medical care for life and so instead, have to be looked after by their partner or parents and it won't cost the state a dime - that's a huge win for the state. This is why, of course, the psych lobby are awarded in the UK (not struck off) for their 'services towards CFS' - by destroying the legitimacy of patients suffering organic disease, untreated. By disease denial and propaganda they have saved the UK, and other countries with tax payer (free) heath care, billions and billions over the years.

This is why they don't want any patients in the UK having ANY ground-breaking drug that validates their disease as organic because if they respond well, they will tell everyone on social media and the press, and then, potentially, millions follow suit. Why risk that, if you can stop any study, by simply refusing funding? So that's what they did and what they do out of habit. £5 million on PACE trial £0 on Rituximab. This is presumably called a ''collaborative approach including everyone''. :lol:

Recently, a UK MS study looking at HERV's using Anti retroviral drugs (which found a benefit) now won't be rolled out across the country due to cost - it also risks 'CFS' and Lyme patients having the same test and testing positive for HERV's. MS can thus stay what it is, a big old mystery. Then, no one has to fund patients on ARV's for life. Simple. In USA and other countries private insurance would pay for the drugs if American patients had insurance, but the vast majority of people in the UK rely on the state for their health-care provision, as it's free at the point of use. Also in the UK, you cannot get insurance if you have a chronic medical illness, you have to sign up first (healthy), and then get sick! When you do, you are given the 'treatment'. For CFS ME, this is of course the ineffective treatment of CBT/GET. No way out of that one.

ME CFS and Rituximab is just a fly in the ointment as far as the state is concerned. As long as no one funds any drug trials in the UK for ME CFS at an infectious pathogen level (Lyme or HERV) or Autoimmune Level (B Cell depletion), the myth that ME CFS is a 'myth' can stay in place, CBT/GET stays, and nothing will change for a good 10 -20 years - saving masses of money and embarrassment for people currently at the very top of their profession.

So to conclude, putting the patients first, is not permitted. Comrade MUPS + PUPS + PPS ordered it after all.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I"ll be honest, anecdotes on rituximab responses from people on PR and from colleagues are not "evidence", and not a sound foundation to decide whether a UK trial should be carried out or not. I know many people who have gotten better/healthy both in Norway and at OMI, but I wont post their accounts here - because it does not matter. Stick to the very sound studies from Norway.

I had my first rtx infusion today, and it went smooth as silk for all 4 of us. More than 150 people have started, and so far: no severe reactions i have heard of as FB-admin. As would be expected based on the numbers you see when rtx is used alone in other diseases.
 

snowathlete

Senior Member
Messages
5,374
Location
UK
When a doctor becomes aware of this type of fairly consistent anecdotal evidence - either directly from the person involved or as 'patient evidence' posted on a forum such as this - in connection with the use of something like rituximab, they also need to be talking to the doctors who have been prescribing rituximab outside a clinic trial

To me this is just comon sense

As I have repeatedly said in previous discussions about the importance of 'patient evidence' in ME/CFS - doctors do need to listen to what their patients are telling them about the safety and efficacy of both drug and behavioural interventions

We all know what happens here in the UK when doctors rely on the evidence in favour of using CBT and GET in everyone with mild or moderate ME/CFS based on what was found in clinical trials and ignore the very differing patient evidence that the MEA collects on an on-going basis

It's common sense to speak to the others prescribing it, sure, but if it's just one group giving it to a handful of patients outside of a formal trial then I don't know if it makes much sense to give it much weight.

I see your point about the dangers of not listening to patients, but the comparison with behavioural therapies in the UK isn't the same. It's on a different scale for a start...tens of thousands of patients have been treated under approved treatment conditions in the health service following trials that are known to have serious flaws both with how they were conducted and how they were reported. As a result, huge numbers of patients have consistently reported adverse events. That's very different to what is being discussed here with Rituxan use in the US.

Anyway, I appreciate you updating us Charles, I'm not trying to give you a hard time, I just don't want limited anecdotal evidence to slow, or deviate, efforts to come up with formal trial results we can put proper faith in.
 

halcyon

Senior Member
Messages
2,482
I did not get the impression that he felt that there were any robust clinical or biolological markers that could (in the present state of knowledge) separate people who were more likely to respond to rituximab and those who were less likely to respond
He is aware of the Scheibenbogen findings I hope. Perhaps too early to call that robust, but finding a UK cohort with these autoantibodies would be a good precursor to a UK rtx trial. If I recall correctly, Dr. Light is already working on identifying US patients with these autoantibodies.
 

Kati

Patient in training
Messages
5,497
In Canada cancer patients benefit from a program called 'compassionate access', which gives them access to drugs which are not normally given for their tumor group, but since they failed the approved treatments, the physicians will suggest other treatments which offers a remote possibility of prolonging survival or perhaps putting them in remission for a while.

Oncology drs use this program all the time. Millions is spent in providing alternative treatment for cancer patients.

Why not us?
Here is the nasty truth:
-because ME could possibly not be that bad, would it?
-because government people would never approve clinical trials for ME, or it would take years just to get approval
-because ME doesn't belong to a medical specialty
-because there is no medical specialty, who is going to have the connections to start a trial and to get funding for that
-because the current evidence (Cochrane) points to CBT and GET as primary treatments. Then why would we do more since it's effective?
- because pharma only funds serious diseases.
And the list goes on.

There is a fine line between doing the right thing for science and doing the right thing for patients. For our disease, we've not made any major leap forward in 30 long years. That's a lifetime.

Back to Canada, the canadian gvernment looks at Cochrane reviews and looks up to the CDC for their ME guidelines if you call them guidelines. Basically they couldn't care less about us.
 

charles shepherd

Senior Member
Messages
2,239
I"ll be honest, anecdotes on rituximab responses from people on PR and from colleagues are not "evidence", and not a sound foundation to decide whether a UK trial should be carried out or not. I know many people who have gotten better/healthy both in Norway and at OMI, but I wont post their accounts here - because it does not matter. Stick to the very sound studies from Norway.

I had my first rtx infusion today, and it went smooth as silk for all 4 of us. More than 150 people have started, and so far: no severe reactions i have heard of as FB-admin. As would be expected based on the numbers you see when rtx is used alone in other diseases.

As I've already explained, Dr Bansal did not say that these reports from people (and their physicians) were going to be a deciding factor as far as a UK trial was concerned. They were being noted as part of an evidence gathering process.

I obviously take the view that we MAY be able to obtain some useful information as to which people are more or less likely to respond to rituximab by talking to patients who have a solid diagnosis of ME/CFS (and their physicians) and have failed to respond, or felt worse, in response to an adequate course of treatment
 

charles shepherd

Senior Member
Messages
2,239
He is aware of the Scheibenbogen findings I hope. Perhaps too early to call that robust, but finding a UK cohort with these autoantibodies would be a good precursor to a UK rtx trial. If I recall correctly, Dr. Light is already working on identifying US patients with these autoantibodies.

I'm sure Dr B is aware of these findings.

He is advising on the UK trial and has been carrying out research into the immunology of ME/CFS (including B cell status) for many years

Reference:

Clin Exp Immunol. 2013 Apr;172(1):73-80. doi: 10.1111/cei.12043.
Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls.
Bradley AS1, Ford B, Bansal AS.
Author information

Abstract
Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by disabling fatigue, headaches, sleep disturbance and several other symptoms. The onset of CFS may follow a viral infection or period of stress. Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity. To date, defects in B cell numbers or function have not been shown in the literature. However, treatment with anti-B cell therapy using Rituximab has recently shown benefit to CFS patients. We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B cell immunophenotyping. We undertook a detailed characterization of the proportions of the different B cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age- and gender-matched healthy controls (HC). CFS patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.

© 2012 British Society for Immunology.
 
Messages
5,238
Location
Sofa, UK
Perhaps less than half of the community will respond? Perhaps those who have sought treatment are long-term patients which has biased the results?
Very good point Bob, I think that's quite likely to be the case and it does appear that those who were non-responders in the Phase 2 trial tended to be the sickest and most long-term patients. (I'm not sure whether they've published anything to that effect, but they've mentioned it once or twice in IiME presentations as I recall).

I do personally agree that it's really not a good idea to be prescribing or getting treated with Rituximab outside of the context of clinical trials at this stage. Fluge and Mella have emphasised that all along, as has Jonathan. So the advice from all the professionals most closely involved in the Rituximab research seems quite clear and consistent on this point, and actually I think everyone could have been a bit more robust in emphasising and explaining this point. As we've now seen, such (expensive) private treatment won't benefit anybody but the individual concerned, but has the potential to undermine efforts to get further research going.

But having read, I think, everything posted on PR from patients treated with Rituximab, I haven't seen anything to make me doubt that the Phase 2 results will hold up well in the Phase 3 trial. It's to be expected that it won't work for everyone, we already know that. We can also expect that the details of the protocol followed will be very significant, and we know that it's a treatment that requires close monitoring and close clinical support by professionals experienced in Rituximab treatment - we also know that accurate diagnosis of ME/CFS is complex, and length of illness seems to be significant - so actually, all things considered, we should expect that the anecdotal reports are not going to be as positive as the trial. So I don't see serious cause for concern in the negative anecdotal reports, and I see ample grounds for continued optimism in the positive anecdotal reports.

So I do think it's quite right and responsible to be discouraging private Rituximab treatment outside the context of a trial at this stage, but for all kinds of other reasons, and not really because of the negative anecdotal reports, so I'm rather surprised to see the MEA emphasising those negative reports. I'm also frustrated that, still, nobody else in the world seems to be working on a study of what seems to me the most promising treatment approach yet for ME/CFS - especially after a significant public campaign that raised funds for a study. It looks like we are going to have to wait for the Norwegian Phase 3 results - and then another year or two of procrastination - before anybody is going to even start to take this forward with another study. Perhaps that's an efficient use of extremely (scandalously) limited funds, in the long run. Perhaps it's also sensibly cautious to be mindful of the political risks of running another trial right now that might fail due to insufficient information about responders, treatment protocol etc...such a trial could make it harder to apply pressure for follow-up and replication when the Nowegian Phase 3 trial lands...so it may indeed be the best plan to wait until we know more before risking a replication study. But that wait probably adds another 2-3 years to the time when this treatment can be available to the patient population at large, so it's very frustrating indeed. Progress in medical research seems unbelievably slow, and frankly the whole system seems hopelessly broken to me, from the point of view of the enormous human needs that are crying out to be met.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
As I've already explained, Dr Bansal did not say that these reports from people (and their physicians) were going to be a deciding factor as far as a UK trial was concerned. They were being noted as part of an evidence gathering process.

I obviously take the view that we MAY be able to obtain some useful information as to which people are more or less likely to respond to rituximab by talking to patients who have a solid diagnosis of ME/CFS (and their physicians) and have failed to respond, or felt worse, in response to an adequate course of treatment

Well the problem with that approach due to the nature of anecdotes, is that the anecdotes picked wont neccesarily reflect the actual response rates from private treatment. Furthermore is the issue of the "evidence" selected, not going through an inclusion process as they are carried out in clinical trials. Who are these patients?

I`m a bit surprised that you think you will find out who will respond based on dialogue, when Fluge & Mella don`t even know yet based on thorough knowledge of participants together with the tests carried out. The results from phase 2 dont point in any direction. Age seems irreleveant, disease length seems irrelevant, trigger seems irrelevant. The only things that may seem to predict responses is the severity of the disease. The amount of response one get might also hinge on how early you respond, as seen with the early responses in the major responders compared to the moderate responders.

With all this being said, of course I dont think anecdotes are completely meaningless, but they should only enjoy a very modest role in the question of the potential of a uk-trial. Unless - people were dying, or getting really ill, which they are not.
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
A lot of good points Mark, only thing i don`t get is how you feel length of disease matters for Rtx-response, personally I don`t see such a trend in the table 1 of the phase 2 PlosOne-article.
 
Messages
5,238
Location
Sofa, UK
A lot of good points Mark, only thing i don`t get is how you feel length of disease matters for Rtx-response, personally I don`t see such a trend in the table 1 of the phase 2 PlosOne-article.
I may be wrong on this Marky, it might have only been severity that Fluge and Mella highlighted and not length of illness. Apologies if I've got that wrong.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I may be wrong on this Marky, it might have only been severity that Fluge and Mella highlighted and not length of illness. Apologies if I've got that wrong.

No worries man, I only remembered cause i was looking at these issues quite recently. I`ve studied that table so much that I might as well make a print of it and hang it over my bed.