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ME/CFS Research (Dr Amolak Bansal) and Management (Dr Charles Shepherd)

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Just something to think about, I am not sure that stress is anything like a discrete concept. I think its a mismash and a confused category, and actually a category mistake. When we try to figure out if someone is stressed, in common usage, we are talking about a symptom not a discrete phenomenon. Within that are many different mechanisms that are the actual basis for what we call stress.

Similar issues arise with depression, fatigue, and pain. These are symptoms of a great many things, and thinking about these things often winds up irrational as a result.
 

Wolfiness

Activity Level 0
Messages
482
Location
UK
Indeed, I believe the technical definition of stress is when a system isn't capable or believes it isn't capable of meeting the demands placed upon it. That covers everything from people to post offices to paper plates.
 

Kati

Patient in training
Messages
5,497
They once believed stress caused stomach ulcers. I was in fact thought in nursing school that the treatment for said ulcers was relaxation and talk therapy.

We know these are no longer valid therapies. We know a bacteria causes stomach ulcers.

Stress is usually the go-to culprit to explain the unexplainable. If only 100 millions was spent to find out cause and subsets, we'd be in a better place.

When you start mentioning stress as causality or as co-factors, then comes the therapies, relaxation, meditation and what not, which is a huge industry, but still won't cure stomach ulcers, amongst others.
 
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Wolfiness

Activity Level 0
Messages
482
Location
UK
Rather concerning anecdotal reports from elsewhere:

(1) The Open Medicine Clinic is providing Rituxan for patients all over the world. I just finished my treatment with very little/no response. Very disappointing, but I felt I had to give it a try. It is very expensive, but there is a pretty good program to help with medication cost if your income is at a certain level and you can prove your insurance won't cover it. Even with the medicine free, the visit is $1500 to $2000 each (x6) plus hundreds of dollars of blood tests. I know there are certain infections they test for before you can go through it, I don't know if Lyme is one of them.


(2) swollen throat

Not Sore. swollen. Maybe swollen bfore rtxn but much worse after. , it's been 8 months on rtxn and over two months since last infusion.

Causing (worse) apnea. Had a home sleep study and apnea is significant.

Anyone else? Any ideas?

gargle with salt water helps the swollen throat a bit.

This seems to help as well:

http://www.1cascade.com/ProductInfo.aspx?productid=4333

Will try this next:

http://www.1cascade.com/ProductInfo.aspx?productid=2726

"Red root is a lymphatic stimulant useful in tonsilitis, sore throats, swollen lymph nodes and fluid-filled cysts. "

Any problems with these? If echinacea stimulates immune sys, bad idea aftr rtxn?


bad sleep

6/12
Pre-rituxan I used to usually sleep through the night, at least the majority of the time, even if not the same quality of sleep as I got pre-CFS. I haven't slept through the night once in the 5.5 months since RituxanIt's getting to be a pretty bad situation. I wake up a lot, and often can't get back to sleep after only 4 hours. I'm really sleepy during the day. When I don't actually wake up, I almost always toss and turn and sort of "half wake up" all the time.

D Ribose didn't used to affect my sleep, but since Rituxan, if I take it during the day (last dose way before bed time) or even in AM only, I lay in bed in a kind of half sleep state where I can't get all the way to sleep.

I had mild sleep apnea before Rituxan, and tha'ts gotten worse. But I think there is something more going on here as well given the "half sleep" (worsened by sugar).

There was a change immediately after Rituxan.

9/12
(update- been 8 mnths and slp a bit better BC of no sugar/carbs for 6hrs bfr bed). But still nt good. Apnea worse.

Curious if anyone else has noticed this?

CFS also wrse

I can't talk. Can't type/text enough to communicate. Haven't had a conversation with someone in 8 months...

It's very sad to hear that this patient's hoped-for treatment has made them worse, but I think I read once that the Norwegian trial participants felt worse for about six months before improving? It clicked in my head because it's similar to what people experience with the guaifenesin protocol.

Guaifenesin made me better for 2.5 days when I started it in 2003, then a lot worse, sometimes almost unendurably, for 7 months, then suddenly a lot better for a couple of years. It's always mystified me because I couldn't reconcile it with the known therapeutic actions of guaifenesin, and my other improvement, with LDN in 2008, was just a straightforward immediate improvement. So it caught my attention when I heard that same response pattern popped up with rituximab.
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I find it bizarre that Bansal are referring to anecdotal reports, instead of the studies in Norway. It`s not the right scientific approach.

Sure, it might be that we wont see the same respons rates in future studies, but this might be closely linked with inclusion criteria. In phase three they included patients with a family history of autoimmune diseases, this to heighten the chances of illuminating the autoimmune subgroup (or at the very least the subgroup where ordinary b-cells are important in the disease mechanism), and I expect they did the same in phase 2. The people taking it privately are MUCH more heteregenous than the study participants, and this could very well affect response rates.

In the studies they have seen transient worsenings in approx 25 %, this is also consistent with what people taking it privately in Norway have reported. It might very well be that Whitney and Bodden for whatever reason relapsed due to rtx alone, but if one bring that up I think one should also point out that these cases are very very rare, and correlation does not imply causation.
 
Messages
15,786
However, feedback relating to people in the UK who have been treated with rituximab in America, as well as US citizens who have been treated with rituximab, has been nowhere near as positive as the results that have been reported from Norway. Consequently, questions are now being asked as to how a UK trial could/should proceed and whether this is the right time to commence a UK trial.

Is he seriously suggesting that Rituximab trials should be scrapped because of anecdotal reports, despite preliminary trials showing it to be effective? If so, I don't think he understands science very well. Trial data is far superior to a few anecdotal reports, especially when those anecdotal reports lack essential data such as diagnostic criteria, symptoms, dosing, etc etc.

This sounds like an attempt to scaremonger, and to shut down the research of a promising biological treatment.
 

user9876

Senior Member
Messages
4,556
I am only aware of anecdotal cases outside Norway where there has not been a response to rituximab and it would, of course, be interesting to know about instances where there has been a positive response

Dr Bansal did not quote any numbers and we were left with the impression that, quite sensibly, the when, where and how of a UK trial is the subject of on-going discussion

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

Rather concerning anecdotal reports from elsewhere:

(1) The Open Medicine Clinic is providing Rituxan for patients all over the world. I just finished my treatment with very little/no response. Very disappointing, but I felt I had to give it a try. It is very expensive, but there is a pretty good program to help with medication cost if your income is at a certain level and you can prove your insurance won't cover it. Even with the medicine free, the visit is $1500 to $2000 each (x6) plus hundreds of dollars of blood tests. I know there are certain infections they test for before you can go through it, I don't know if Lyme is one of them.


(2) swollen throat


Not Sore. swollen. Maybe swollen bfore rtxn but much worse after. , it's been 8 months on rtxn and over two months since last infusion.

Causing (worse) apnea. Had a home sleep study and apnea is significant.

Anyone else? Any ideas?

gargle with salt water helps the swollen throat a bit.

This seems to help as well:

http://www.1cascade.com/ProductInfo.aspx?productid=4333

Will try this next:

http://www.1cascade.com/ProductInfo.aspx?productid=2726

"Red root is a lymphatic stimulant useful in tonsilitis, sore throats, swollen lymph nodes and fluid-filled cysts. "

Any problems with these? If echinacea stimulates immune sys, bad idea aftr rtxn?


bad sleep

6/12
Pre-rituxan I used to usually sleep through the night, at least the majority of the time, even if not the same quality of sleep as I got pre-CFS. I haven't slept through the night once in the 5.5 months since RituxanIt's getting to be a pretty bad situation. I wake up a lot, and often can't get back to sleep after only 4 hours. I'm really sleepy during the day. When I don't actually wake up, I almost always toss and turn and sort of "half wake up" all the time.

D Ribose didn't used to affect my sleep, but since Rituxan, if I take it during the day (last dose way before bed time) or even in AM only, I lay in bed in a kind of half sleep state where I can't get all the way to sleep.

I had mild sleep apnea before Rituxan, and tha'ts gotten worse. But I think there is something more going on here as well given the "half sleep" (worsened by sugar).

There was a change immediately after Rituxan.

9/12
(update- been 8 mnths and slp a bit better BC of no sugar/carbs for 6hrs bfr bed). But still nt good. Apnea worse.

Curious if anyone else has noticed this?

CFS also wrse

I can't talk. Can't type/text enough to communicate. Haven't had a conversation with someone in 8 months...

One concern I have about the OMI program and using data from it is that people are travelling a long way in order to have treatments and this in itself could cause a relapse.

It worries me if a trial is being ruled out due to anecdotal stories which are unclear told on the internet. It is unfortunate that OMI are not publishing overall figures but if the response rate is 2/3 and then there we should expect some non-responders. A trial to replicate seems the right approach to try to replicate figures.
 

bertiedog

Senior Member
Messages
1,738
Location
South East England, UK
During the research section of the meeting Dr Bansal refered to two beneficial effects of exercise - endorphin release and pain and a substance involved in neuronal repair called brain derived neurotrophic factor/BDNF - and did nothing more than say that these are two important aspects of muscle function that need to be considered when we look at research into activity/energy management

I know this can be true PROVIDED I am not in a downturn or crash situation. On a normal day I always feel better for a good 20-25 minute walk in the park with my dog. Usually I am out for 30 minutes but that always includes a short sit-down. I feel energised and have a sense of well being.

However if my energy is poor and I am not feeling relatively strong then only a 15 minute walk will take it out of me. I will feel weak in my legs, probably dizzy and my brain is firing off negative messages to me that I need to sit down.

I am lucky in that I have my endocrine system supported so I bounce back pretty quickly and also have had a lot of support for my immune system so on most days I can have an enjoyable, beneficial walk but without these things I spent my life on the couch. Finally the other thing that makes a huge difference in my ability to walk for an average of 8500-9000 steps daily is the use of my oxygen concentrator 3 times daily after each meal or after exercise. I don't understand why more isn't mentioned of the help these can give us in order to be able to have at least some exercise.

Pam
 

charles shepherd

Senior Member
Messages
2,239
Is he seriously suggesting that Rituximab trials should be scrapped because of anecdotal reports, despite preliminary trials showing it to be effective? If so, I don't think he understands science very well. Trial data is far superior to a few anecdotal reports, especially when those anecdotal reports lack essential data such as diagnostic criteria, symptoms, dosing, etc etc.

This sounds like an attempt to scaremonger, and to shut down the research of a promising biological treatment.

You appear to have misunderstood the points that were being made in the summary of this meeting

Clinical trials should, of course, be providing the 'Gold Standard' information that is required when it comes to making important decisions as to whether a drug (or a behavioural) treatment is safe and effective and whether something like rituximab should then be licensed for use in ME/CFS (and recommended for use by NICE here in the UK)

And normally they do

But there are exceptions……..

In the case of ME/CFS, the conflicting evidence from clinical trials and the 'patient evidence' in relation to CBT and GET immediately springs to mind.

And there are other instances where clinical trials have dismissed forms of treatment in ME/CFS where the 'patient evidence' indicates that they could be safe and effective (e.g. vitamin B12)

So you also have to take notice of anectodatal patient evidence, as as well as anecdotal evidence from clinicians, when deciding how to move forward with a clinical trial that is going to provide further evidence on safety and efficacy in the case of a very costly treatment such as rituximab - where there are also issues and concerns relating to both short term and long term adverse effects

I take the view (along with many of my clinical colleagues) that in our current state of knowledge the use of rituximab in ME/CFS should normally be restricted to properly organised clinical trials. This is partly because rituximab is a drug that has the potential to cause very serious side-effects. So I don't think it should be used outside clinical trials until we have further information on safety, efficacy and we know more about which patients might or might not respond

However, out in the real world, patients in the US are being prescribed rituximab outside clinical trials and they are reporting their experiences to clinicians and on the internet - some of which are very disappointing or concerning

All that was being said at the meeting was that this 'patient evidence' also has to be noted and discussed.

It would be negligent not to do so.

The MEA continues to believe that there should be high quality clinical trials of rituximab taking place outside Norway to see if other groups can replicate the findings relating to safety and efficacy (as well as identifying sub-groups that may respond better/worse than others)

Consequently, our offer to provide around £60,000 (possibly more) to help fund a clinical trial of rituximab here in the UK remains on the table
 

charles shepherd

Senior Member
Messages
2,239
One concern I have about the OMI program and using data from it is that people are travelling a long way in order to have treatments and this in itself could cause a relapse.

It worries me if a trial is being ruled out due to anecdotal stories which are unclear told on the internet. It is unfortunate that OMI are not publishing overall figures but if the response rate is 2/3 and then there we should expect some non-responders. A trial to replicate seems the right approach to try to replicate figures.

My understanding is that the patients who have been treated with rituximab during the past few years at the OMI are not part of a formal clinical trial - I certainly cannot find any registration of a clinical trial

It would, of course, be very interesting to have this 'clinical evidence' made available
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
In the case of ME/CFS, the conflicting evidence from clinical trials and the 'patient evidence' in relation to CBT and GET immediately springs to mind.

If I understand you correctly here, I strongly disagree. Anecdotal reports on CBT and GET long stood as the foundation for conclusions on it`s efficancy by health workers and governments. PACE and FINE both showed zero objective improvements, and therefore CBT and GET so far has been proven not to work, by the researchers who were adamant to make them work. There is no conflict between anecdotes on CBT and GET, studies on CBT and GET, and studies indicating that rituximab works for ME/CFS. Rituximab seems to work for some, while CBT and GET does not.

"And there are other instances where clinical trials have dismissed forms of treatment in ME/CFS where the 'patient evidence' indicates that they could be safe and effective (e.g. vitamin B12)"

True, but that would in reality also be the case for PACE and FINE for CBT and GET.

"So you also have to take notice of anectodatal patient evidence, as as well as anecdotal evidence from clinicians, when deciding how to move forward with a clinical trial that is going to provide further evidence on safety and efficacy in the case of a very costly treatment such as rituximab - where there are also issues and concerns relating to both short term and long term adverse effects"


No, there`s no sound reason to do so when the only place adverse effects are consistently reported is from Haukeland. Anecdotal reports will represent a completely skewed picture of what adverse effects one could expect from rituximab for ME/CFS.

"I take the view (along with many of my clinical colleagues) that in our current state of knowledge the use of rituximab in ME/CFS should normally be restricted to properly organised clinical trials. This is partly because rituximab is a drug that has the potential to cause very serious side-effects. So I don't think it should be used outside clinical trials until we have further information on safety, efficacy and we know more about which patients might or might not respond"

Agreed, but it`s important to remember that the actual risk for serious side effects with rituximab alone, is almost as low as the one you get from taking paracetamol.

"However, out in the real world, patients in the US are being prescribed rituximab outside clinical trials and they are reporting their experiences to clinicians and on the internet - some of which are very disappointing or concerning"

But the problem is that such reporting is not consistent, and therefore not information that should be relevant in the question of going forward with a trial on rituximab or not.
 
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Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
My understanding is that the patients who have been treated with rituximab during the past few years at the OMI are not part of a formal clinical trial - I certainly cannot find any registration of a clinical trial

It would, of course, be very interesting to have this 'clinical evidence' made available

As far as I understand there is no active reporting of adverse effects or responses, so there is not really any data available anyway i think.
 

charles shepherd

Senior Member
Messages
2,239
If I understand you correctly here, I strongly disagree. Anecdotal reports on CBT and GET long stood as the foundation for conclusions on it`s efficancy by health workers and governments. PACE and FINE both showed zero objective improvements, and therefore CBT and GET so far has been proven not to work, by the researchers who were adamant to make them work. There is no conflict between anecdotes on CBT and GET, studies on CBT and GET, and studies indicating that rituximab works for ME/CFS. Rituximab seems to work for some, while CBT and GET does not.

"And there are other instances where clinical trials have dismissed forms of treatment in ME/CFS where the 'patient evidence' indicates that they could be safe and effective (e.g. vitamin B12)"

True, but that would in reality also be the case for PACE and FINE for CBT and GET.

"So you also have to take notice of anectodatal patient evidence, as as well as anecdotal evidence from clinicians, when deciding how to move forward with a clinical trial that is going to provide further evidence on safety and efficacy in the case of a very costly treatment such as rituximab - where there are also issues and concerns relating to both short term and long term adverse effects"


No, there`s no sound reason to do so when the only place adverse effects are consistently reported is from Haukeland. Anecdotal reports will represent a completely skewed picture of what adverse effects one could expect from rituximab for ME/CFS.

"I take the view (along with many of my clinical colleagues) that in our current state of knowledge the use of rituximab in ME/CFS should normally be restricted to properly organised clinical trials. This is partly because rituximab is a drug that has the potential to cause very serious side-effects. So I don't think it should be used outside clinical trials until we have further information on safety, efficacy and we know more about which patients might or might not respond"

Agreed, but it`s important to remember that the actual risk for serious side effects with rituximab alone, is almost as low as the one you get from taking paracetamol.

"However, out in the real world, patients in the US are being prescribed rituximab outside clinical trials and they are reporting their experiences to clinicians and on the internet - some of which are very disappointing or concerning"

But the problem is that such reporting is not consistent, and therefore not information that should be relevant in the question of going forward with a trial on rituximab or not.

I think we are going to have to agree to disagree on most of the points you make!

But I will respond to one observation:

"Agreed, but it`s important to remember that the actual risk for serious side effects with rituximab alone, is almost as low as the one you get from taking paracetamol."

As we all know, rituximab is a drug that can cause a range of side-effects, including serious side-effects in both the short term (even life threatening) and in the long term. All the indications so far from the work in Norway indicate that most people with ME/CFS are not having any significant problems (in the short term) and can tolerate this drug. However, the numbers are still very small, and may not be representative of other patient groups with ME/CFS. So the simple answer at the moment is that rituximab appears to be safe to use in ME/CFS. But this can only be confirmed if these findings are replicated in much larger clinical trials that are carried out in a number of independent centres.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I think we are going to have to agree to disagree on most of the points you make!

But I will respond to one observation:

"Agreed, but it`s important to remember that the actual risk for serious side effects with rituximab alone, is almost as low as the one you get from taking paracetamol."

As we all know, rituximab is a drug that can cause a range of side-effects, including serious side-effects in both the short term (even life threatening) and in the long term. All the indications so far from the work in Norway indicate that most people with ME/CFS are not having any significant problems (in the short term) and can tolerate this drug. However, the numbers are still very small, and may not be representative of other patient groups with ME/CFS. So the simple answer at the moment is that rituximab appears to be safe to use in ME/CFS. But this can only be confirmed if these findings are replicated in much larger clinical trials that are carried out in a number of independent centres.

Fair enough, Charles :) The beauty of democracy, and individual time management.

I would however appreciate an eloberation of how anecdotes can be justified as relevant, in the above mentioned circumstances.

I concur with your latest comment.
 

charles shepherd

Senior Member
Messages
2,239
Fair enough, Charles :) The beauty of democracy, and individual time management.

I would however appreciate an eloberation of how anecdotes can be justified as relevant, in the above mentioned circumstances.

I concur with your latest comment.

Anecdotes = patient and clinician evidence

I take the view that doctors need to listen to what patients (and their medical colleagues) tell them about what helps/does not help in relation to treatment and management of ME/CFS!
 

charles shepherd

Senior Member
Messages
2,239
One of the big unknowns in relation to the possibility of treatment with rituximab in a neuroimmune disease like ME/CFS (where there is also evidence of reactivated viral infection) is what effect LONG TERM treatment might have on an important (but fortunately rare) neurological side-effect known as progressive multifocal leukoencephalopathy (PML)

PML and Rituximab: What Rheumatologists Should Know
July 25, 2013 | Rheumatic Diseases
By Leonard Calabrese DO

Prior to 2005, progressive multifocal leukoencephalopathy (PML) was the domain of HIV specialists, oncologists, or physicians caring for transplant recipients. Then, a tectonic change occurred. PML was discovered among patients taking the biologic agent natalizumab for multiple sclerosis. Within two years, we found that the disease occurred rarely with a variety of immunosuppressive agents, including rituximab.1

As there is no simple and effective therapy for this often-fatal condition, it is important for physicians who prescribe biologics to remain informed. Here are the basics and the latest facts:

PML is a rare, typically fatal opportunistic infection secondary to JC virus (a polyoma virus originally called John Cunningham virus). Classically, it is seen in patients with compromised immune systems. Most patients (about 95%) have HIV infection, are on combination chemotherapy for cancer, or are transplant recipients. Approximately 2-5% of patients with PML have underlying autoimmune or autoinflammatory disorders, and are on or have been treated with immunosuppressives. PML occurs rarely in normal hosts and can also arise on rare occasions in the absence of iatrogenic immunosuppression, generally associated with a comorbidity such as sarcoidosis or chronic liver disease.1

With approval of the biologic agent natalizumab for the treatment of multiple sclerosis, which represented a major clinical advance for that condition, PML re-emerged as an iatrogenic threat. In 2007, shortly after review of 24-month data on natalizumab,2 cases of PML were identified, followed quickly by a third case. This led to temporary suspension of the drug. Over time it was re-introduced with aggressive risk mitigation. Over 350 cases have been reported worldwide by now. As a result, there is now a much greater focus upon PML in the immunosuppressed patient in general, and more specifically in those patients on biologic therapies. (A second and small chapter in this history was the identification of 4 cases of PML associated with the T cell directed drug efalizumab, used to treat psoriasis. This agent was pulled from the market voluntarily.)

PML has also been associated with other immunosuppressive agents including rituximab, frequently in patients with systemic lupus erythematosus (SLE). In 2007, our group found that the disease occurred rarely with a variety of immunosuppressive agents.2 Of note, SLE patients appeared to be affected disproportionately. Two patients with SLE had been exposed to rituximab, and over time it was appreciated that rituximab was associated with PML. One systematic review that used a sophisticated search mechanism for rare diseases reported 57 cases.3 The majority were patients who had been prescribed rituximab along with chemotherapy to treat malignancy.

It remains unexplained why PML arises as a rare complication of therapy with immunosuppressive agents. Since the original cases reporting PML in SLE patients, a total of 6 cases have been described in patients treated with rituximab for rheumatoid arthritis (RA), and summarized in a recent systematic review of the FDA Adverse reporting System.4 An analysis of several of these cases revealed no obvious cofactors associated with the development of PML, such as age, dose, or duration of treatment. In this analysis of all cases of PML occurring in patients with rheumatic diseases from 1997-2010, a total 34 confirmed cases were described, including 14 exposed to rituximab. Again, SLE was the predominant underlying diagnosis.4 PML was found in only one instance of exposure to a TNF inhibitor.

In terms of aggregate risk, PML remains a very rare complication in rheumatic diseases in general and in RA in particular. For RA patients treated with rituximab, the risk is extremely low, with recent incidence estimates in the range of 5/100,000 patients exposed to the drug. In comparison, the incidence of PML in natalizumab-exposed patients is approximately 1/1000. In the case of natalizumab, cofactors such as dose, duration, and co-therapy contribute to the risk. It can be calculated that for a JC virus-infected patient with MS treated with natalizumab for a long period (>24 months) who has a history of prior immunosuppressive exposure, the risk may approach 1/100.5 Clearly, these are significantly different magnitudes of risk.

From my perspective, PML is very rare prevalent risk for all patients who are on heavy immunosuppressives including rituximab, especially in the setting of SLE. Given the difference in levels of risk just described, I do not believe that a risk-mitigation strategy (such as serologic testing for underlying JC infection, being used to stratify risk in MS) can be justified for patients with rheumatic diseases.

While I advocate vigilance in terms of carefully evaluating new-onset suspicious focal and diffuse neurologic dysfunction, as we have summarized elsewhere,6 PML is not a reason to eschew effective therapy when needed.

Much remains to be learned about the biology and natural history of JC infection. Unfortunately, there is no effective therapy, short of reconstituting the immune system. So rheumatologists will have to stay tuned in.2
 

msf

Senior Member
Messages
3,650
Interesting stuff about JC virus and Rituximab, Dr. Shepherd. It´s really odd how it can make you very susceptible to JC virus, Hep C (I think), but not to just any virus or bacteria.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Anecdotes = patient and clinician evidence

I take the view that doctors need to listen to what patients (and their medical colleagues) tell them about what helps/does not help in relation to treatment and management of ME/CFS!

That`s a great stance, I guess we simply have conflicting opinions on the value of anecdotal "evidence" compared to trial evidence. I agree that there are many questions regarding safety with long term treatment, but it seems to be much more important when rituximab is used with other immunosuppressives.
 

charles shepherd

Senior Member
Messages
2,239
Interesting stuff about JC virus and Rituximab, Dr. Shepherd. It´s really odd how it can make you very susceptible to JC virus, Hep C (I think), but not to just any virus or bacteria.

Interesting (and rather concerning) drug alert from the FDA in relation to viral reactivation in two people who had been taking rituximab for SLE (where approx 10,000 patients have been treated with rituximab):

Information for Healthcare Professionals: Rituximab (marketed as Rituxan)
FDA ALERT [12/2006]: This Alert highlights important emerging safety information about Rituxan. Two patients have died after being treated with Rituxan for systemic lupus erythematosus (SLE). The cause of death was a viral infection of the brain called progressive multifocal leukoencephalopathy (PML) that is caused by reactivated JC virus. Latent JC virus is present in about 80 percent of adults.

Rituxan is a powerful immunosuppressant that eliminates mature circulating B-cells for up to nine months. Rituxan is approved for CD20-positive, B-cell, non-Hodgkins lymphoma and for moderately-to severely-active rheumatoid arthritis when there has been inadequate response to other treatments. Rituxan is being studied for other indications, and is prescribed off-label for other serious diseases and conditions such as SLE. The sponsor estimates that approximately 10,000 patients with SLE have been treated with Rituxan. Reactivation or exacerbation of viral infections including JC virus leading to PML may occur when patients receive Rituxan for any reason. FDA is working with the sponsor to gather additional information about the occurrence of PML in patients treated with Rituxan and to strengthen the Warnings about the risk of PML in the product labeling for Rituxan. Patients who have been treated with Rituxan and present or develop new neurological signs or symptoms should be evaluated for PML.
 

charles shepherd

Senior Member
Messages
2,239
That`s a great stance, I guess we simply have conflicting opinions on the value of anecdotal "evidence" compared to trial evidence. I agree that there are many questions regarding safety with long term treatment, but it seems to be much more important when rituximab is used with other immunosuppressives.

Anecdotal evidence in science and medicine (from elsewhere):

But should anecdotes play any role in medical evidence? Yes, but a very minor and clearly defined one. Anecdotes, with all their weaknesses, are real life experience. It is possible that a treatment does in fact work and personal experience may be the first indication that there is a meaningful biological effect in play. But here are two limiting factors in how anecdotes should be incorporated into medical evidence:

The first is that anecdotes should be documented as carefully as possible. This is a common practice in scientific medicine, where anecdotes are called case reports (when reported individually) or a case series (when a few related anecdotes are reported). Case reports are anecdotal because they are retrospective and not controlled. But it can be helpful to relay a case where all the relevant information is carefully documented – the timeline of events, all treatments that were given, test results, exam findings, etc. This at least locks this information into place and prevents further distortion by memory. It also attempts to document as many confounding variables as possible.

The second criterion for the proper use of anecdotes in scientific medicine is that they should be thought of as preliminary only – as a means of pointing the way to future research. They should never be considered as definitive or compelling by themselves. Any findings or conclusions suggested by anecdotal case reports need to be later verified by controlled prospective clinical studies.

Understanding the nature and role of anecdotes is vital to bridging the gap between the proponents of science-based medicine and believers in dubious or sectarian health practices (as well as the public at large). In my experience it is often the final point of contention between these two camps.

It is interesting to note that the scientific community has long ago made up its collective mind about the weaknesses and role of anecdotes. Logic and the lessons of history speak very clearly on this issue. But there are forces at work today that want to turn back the clock on scientific progress – they want to bring back anecdotes as a reliable source of medical evidence, essentially returning to the pre-scientific era of medicine. In some cases this is done out of frustration – that controlled scientific data has not validated a prior strongly held belief. In other cases it seems to be a calculated attempt to lower the bar of evidence to admit treatments that have not been validated by solid scientific evidence. In either case, this is not in the best interest of the health of the public.