Harriet Hall CFS: Rituximab Revisited in Science-Based Medicine

[Cheshire]

Three years ago I wrote about an experimental treatment for chronic fatigue syndrome (CFS): rituximab (brand name Rituxan). I was concerned that doctors who offered it, like Andreas Kogelnik, were jumping the gun by offering it before the evidence was in, and that they might be putting patients at risk. A correspondent who has been following the CFS forums asked me to revisit this issue. She sent me links to forum posts indicating that Dr. Kogelnik is treating CFS patients with the drug, that they are not being enrolled in clinical trials, that information about results is not available, and that at least one patient may have developed a life-threatening side effect. I want to stress that I don’t have any evidence that those statements are true. These are only posts on a forum, and I have no way to verify the information. I tried to get more information from Dr. Kogelnik’s clinic, but was unsuccessful. Nevertheless, even if everything in those forum posts is false, I think the issue is serious enough to bring it to the attention of the public again. My purpose is to provide accurate information about rituximab and to get people to think about the principles involved, not to make claims or accusations or cast any blame.

https://www.sciencebasedmedicine.org/chronic-fatigue-syndrome-rituximab-revisited/

Very weird and perplexing article, to say the least...

FYI Harriet Hall also wrote this article: https://www.sciencebasedmedicine.org/iom-recommends-replacing-cfs-with-seid/
Discussed here: http://forums.phoenixrising.me/inde...iom-recommends-replacing-cfs-with-seid.35963/

Edit: she uses PR material and posts made by Whitney Dafoe.

 

[Gijs]

Maybe she can write an article about the PACE trial and CBT/GET as well. I hope she read this topic too. But i don't think so.

 

[MeSci]

I'd like to hear what @Jonathan Edwards thinks/knows about this.

 

[A.B.]

When I wrote about this before, the evidence for rituximab in CFS boiled down to a case series of three, and one small randomized controlled trial in 2008. That RCT was negative for the primary end-point of self-reported symptoms at 3 months but 2/3 of the subjects showed a delayed transient improvement after 6-10 months of followup. The protocol in that study was not the same as the protocol Dr. Kogelnik was using.

Key information missing here:

* There was a placebo control group and blinding. Omitting this will lead readers to the conclusion that the response may have merely been a placebo effect.

* While the primary endpoint was negative, the delayed transient response is consistent with an autoimmune disease involving pathogenic B cells.

* While I'm too tired to go over the study and various articles to find out how many patients in that trial had a sustained remission, I suspect there were at least some. Characterising the response to Rituximab as transient in general is inaccurate. The later open label trial (1) reported sustained remission even 3 years after treatment in 11 out of 18 responders. This is unlikely to be entirely due to regression to the mean. Again I'm too tired to dig out details but ME/CFS in a patient sample that has been sick for a while is unlikely to spontaneously go into remission like this.

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488509/

 

[chipmunk1]

like Andreas Kogelnik, were jumping the gun by offering it before the evidence was in, and that they might be putting patients at risk

and CBT was never used before PACE.

 

[user9876]

Key information missing here:


* While I'm too tired to go over the study and various articles to find out how many patients in that trial had a sustained remission, I suspect there were at least some. Characterising the response to Rituximab as transient in general is inaccurate. The later open label trial (1) reported sustained remission even 3 years after treatment in 11 out of 18 responders. This is unlikely to be entirely due to regression to the mean. Again I'm too tired to dig out details but ME/CFS in a patient sample that has been sick for a while is unlikely to spontaneously go into remission like this.

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488509/

But wouldn't we expect the response to be transient in that as b cells build up again and start the production of antibodies then the effects would go if it were triggered by antibodies.

 

[A.B.]

But wouldn't we expect the response to be transient in that as b cells build up again and start the production of antibodies then the effects would go if it were triggered by antibodies.

The theory is that wiping them out completely leads to remission, wiping them out partially leads to a transient improvement.

 

[A.B.]

By the way I have no interest in defending Kogelnik, I just thought the parts aboutthe evidence to date was biased (there are some other parts which were probably also biased but I don't want to investigate further at the moment). A critique of Kogelnik would be more credible if the rest was unbiased.

 

[snowathlete]

Interesting, but it's mainly speculation.
Some ppl who may have MECFS may have been given Rituximab in the U.S. under an unknown protocol that wasn't part of a formal trial and some of them may have got worse as a result but we don't know.

On the other hand, the formal trials we do know about and can base science on are very promising. Also failed to mention there is a UK trial starting and rumours of the NIH funding a U.S. trial.

I also think the stuff about adverse effects was not as balanced as it should have been because fatalities from Ritux, although they can occur, are rare and there is no evidence to show its any higher in MECFS than anything else.

Pleased to see coverage of MECFS. Why you wouldn't cover the currently bigger story about the dodgy PACE trial though I really don't know.

 

[Marky90]

What a balanced article - not.

First off - exercise intolerance is not incompatible with an autoimmune theory.
Also, if Whitney Dafoe had PML he would have been dead by now.
Furthermore: There is a big study on PML incidence in RA, the conlusion was that 1 in 25000 got it approx. And they were on other chemo to if i remember correctly.
And why is it not mentioned that infections due to rtx can be treated?

 

[A.B.]

I also think the stuff about adverse effects was not as balanced as it should have been because fatalities from Ritux, although they can occur, are rare and there is no evidence to show its any higher in MECFS than anything else.

As far as I know the side effects also depend a lot on what disease patients have.

Also the article conveniently doesn't mention how often progressive multifocal leukoencephalopathy actually occurs. From what I remember it's very rare.

 

[Sidereal]

Comment under the article:

shewolfdc • 30 minutes ago
This is the only voice of reason I have found out there on this horrible drug. Back in the 1960s I was diagnosed with Rhematoid Arthritis. This was long before things like RH factor used today to diagnose it existed. But the label stayed on me for many years and was only dropped when I tested negative for RH factor. Eventually I spent six hours with an MS specialist at Georgetown who diagnosed me with ME/CFS based on exercise intolerance and the results of tests ranging from a hospital sleep study, blood work for viruses and lymes disease, MRIs and a spinal tap. I bring all this up because before the RA diagnosis was abandoned, I was put on rituximad and it is the devil. My brain has never been the same since. Parts of my brain are foggy in ways it never was before. This isn't standard brain fog but rather is only in one aspect of my brain that I feel was damaged by this drug. I also had severe, life threatening reactions during the infusion process that resulted in nurses having to scurry to shoot me with drugs to save me. In all I have four, four-hour long infusions over two years. Three with reactions. The last was so bad I quit the drug altogether. It has really concerned me that so many ME/CFS patients, out of desperation, have clung to the hope that this horrible drug was the answer. It is not. I do have ME/CFS and this drug never helped me for once second and did indeed make me worse. I was so hopeful at the time. But this is a dangerous and expensive dead end for ME/CFS patients. Please think long and hard before trying this drug.

 

[Marky90]

As far as I know the side effects also depend a lot on what disease patients have.

Also the article conveniently doesn't mention how often progressive multifocal leukoencephalopathy actually occurs. From what I remember it's very rare.

It`s extremely rare http://www.ncbi.nlm.nih.gov/pubmed/21555606

 

[Nielk]

Does every article about ME/CFS have to be about PACE to be of value? It is important to look at all the information that is available (or suppressed) so far about Rituximab for ME/CFS patients. The writer warns that because Dr. Kogelnik has not been forthright about his experience administrating Rituximab to patients in the US, we do not really know how many have been helped in a measurable way.

I have taken Rituximab over a year ago for my new diagnosis of RA. It did not help me, but it didn't harm me either. I posted about my experience here. At the time, I was searching for stories from Dr. Kogelnik's patients but, found very little. I did find some patients who claimed their ME has declined since taking the drug. We should not discount these experience just because we desire the outcome to be different.

I do hope that a percentage of patients will ultimately be helped by Rituximab because so far we have so little in successful treatments but, we should not jump the gun and put down those that report on the current state of knowledge.

 

[Marky90]

I do hope that a percentage of patients will ultimately be helped by Rituximab because so far we have so little in successful treatments but, we should not jump the gun and put down those that report on the current state of knowledge.

Problem is she didn`t though, her representation of rtx adverse effects makes the drug sound more dangerous than it actually is.

 

[greeneagledown]

Everything people have said about being cautious with using this drug experimentally in ME/CFS is reasonable. And if this disease weren't so debilitating, or if there were other treatments already available, it would be ridiculous for anyone to use Rituximab prior to publication of a successful phase 3 study. But this disease is wretched and there are no known effective treatments. That has to factor into the risk/reward calculus here. The phase 3 study probably isn't going to be published until 2018 and in the meantime, people are losing years of their lives.

It may well be the case that Rituximab makes some patients permanently worse. But judging from the preliminary results from Norway, the likelihood of someone going into remission is FAR higher than the likelihood of someone getting permanently worse.

 

[MeSci]

Since Harriet and her female correspondent (we can all easily guess who) follow Phoenix Rising forums so closely she might consider writing a piece on graded exercise therapy

Am I the only one who can't guess who this person is?

 

[jimells]

It may well be the case that Rituximab makes some patients permanently worse.

Assuming that the unknown patients did get worse, how does anyone "know' it was the Rituximab and not the natural progression of the patient's illness? No matter what I do or don't do, my illness is gradually getting worse. I can maybe affect the speed of the decline, but not stop or reverse it.

I wonder just what clinical trials the author thinks these patients could've been enrolled in. And what about patient privacy? The author seems to think spreading acknowledged gossip is more important.

 

[Marky90]

Assuming that the unknown patients did get worse, how does anyone "know' it was the Rituximab and not the natural progression of the patient's illness? No matter what I do or don't do, my illness is gradually getting worse. I can maybe affect the speed of the decline, but not stop or reverse it.

I wonder just what clinical trials the author thinks these patients could've been enrolled in. And what about patient privacy? The author seems to think spreading acknowledged gossip is more important.

That is a very good point. A modest percentage of people with ME get worse every year, even though they keep their activity levels down. It then follows as likely that a certain percentage with ME who dont respond, will get worse.

And what do we learn in school?
Correlation does not imply causation.

One thing we do know though: About 25 % of the patients taking rtx goes through a transient worsening, that can last weeks, even months.

 

[jimells]

@A.B. Great response to the essay. Thank you.