Harriet Hall CFS: Rituximab Revisited in Science-Based Medicine

[Marky90]

I'd like to know if you have any reference for this? I never got this impression myself although they did joke that they hoped the rtx trial wouldn't be in vain if cyclophosphamide is successful.
Even if cyclophosphamide is successful it is likely many years away from a phase 3 trial and also given the side effects it would seem likely that rtx would be preferred first line treatment unless it is known that a patient won't respond.



I think everyone would agree that there is a risk but some people decide it's a risk worth taking. It's not an easy decision by any means and the participants in the phase three trial are taking this risk on all our behalf.

Interesting. Could you elaborate on this @Jonathan Edwards ? I had not really considered that, and thought I could try another regime in some years when b-cells are up again..

 

[Marky90]

I think Marky90's point about the risk of the disease progressing such that Rituximab is no longer effective for them by the time it becomes available...I agree that's quite a strong argument. With some high quality information coming down the road in about 2 years, though, I tend to think it would be a safer choice for most people to wait for the results of that study.

Yeah, I think i might have waited if I knew my disease would stay at status quo..

But after learning that Jameson Hill, a vibrant hopeful young man in the new ME-documentary, apparantly suddenly have become completely bedbound - it got me thinking. I know the progressive kind is a minority, but it is a nightmarish prospect, and I want to avoid it if possible..

 

[Jonathan Edwards]

Interesting. Could you elaborate on this @Jonathan Edwards ? I had not really considered that, and thought I could try another regime in some years when b-cells are up again..

I think it is all a matter of speculation as to what happens next. The risks of trying these treatments now are probably not great but the better organised and documented trials are the more we will know.

 

[BurnA]

I think it is all a matter of speculation as to what happens next. The risks of trying these treatments now are probably not great but the better organised and documented trials are the more we will know.

Do you have any theory as to why some people may deteriorate after rtx treatment ?

 

[BurnA]

Yeah, I think i might have waited if I knew my disease would stay at status quo..

But after learning that Jameson Hill, a vibrant hopeful young man in the new ME-documentary, apparantly suddenly have become completely bedbound - it got me thinking. I know the progressive kind is a minority, but it is a nightmarish prospect, and I want to avoid it if possible..

It's true, sometimes not knowing what the future holds is the worst part about this disease. I can function enough that I can still work and therefore my life isn't completely ruined but it's the prospect of not being able to work that scares the hell out of me everyday and makes me want to try rtx.

 

[Marky90]

I think it is all a matter of speculation as to what happens next. The risks of trying these treatments now are probably not great but the better organised and documented trials are the more we will know.

Thanks, I agree with you, however i wondered if there is any experience with regards to rtx working less well the second time around in e.g. RA? I don`t want to miss out on a future protocol or drug cocktail, if you catch my drift..

 

[Jonathan Edwards]

Do you have any theory as to why some people may deteriorate after rtx treatment ?

People with ME/CFS appear to be intolerant of all sorts of things and we do not know why. I think it unlikely that rituximab would make people worse for any specific reason relating to the action of rituximab.

One thing that seems a bit strange in the Hall piece is to suggest that rituximab is inappropriate for ME/CFS, presumably because ME/CFS is not a serious enough condition, but then to suggest that rituximab might make ME/CFS so much worse that the person was terribly ill, so it should not be used because ME/CFS can become seriously disabling. Infection really is not a common problem with rituximab, even if very rarely opportunistic infections can occur, unless the person already has a serious immunodeficiency. The whole thing was not thought through.

 

[Marky90]

People with ME/CFS appear to be intolerant of all sorts of things and we do not know why. I think it unlikely that rituximab would make people worse for any specific reason relating to the action of rituximab.

One thing that seems a bit strange in the Hall piece is to suggest that rituximab is inappropriate for ME/CFS, presumably because ME/CFS is not a serious enough condition, but then to suggest that rituximab might make ME/CFS so much worse that the person was terribly ill, so it should not be used because ME/CFS can become seriously disabling. Infection really is not a common problem with rituximab, even if very rarely opportunistic infections can occur, unless the person already has a serious immunodeficiency. The whole thing was not thought through.

One thing i wondered about is the transient worsenings.. Quite a lot of the patients taking rtx privately in norway are experiencing this. Are b-cells important in restricting the profileration potential of potential remaining autoimmune plasma cells? Or are worsenings more likely to be due to some unknown unknown immune reaction similar to side effects after intravenous gammaglobulins, as fluge and mella have proposed.

Would be interesting to hear your thoughts on this!

 

[Marky90]

Sorry for the immunobabble, maybe you understood what I would ask if I knew more immunology

 

[Sasha]

Jonathan Edwards has made the point on this forum that there's a particular risk of getting Rituximab treatment right now, which I think is an important point worth emphasising: while we're at the stage where researchers are refining the protocol, we don't really know what the most effective treatment regime is and what the long-term effects may be. But as I recall it, Jonathan noted that in RA, to some extent you may be 'using up your bullets' every time you try Rituximab treatment. Somebody getting treatment now might find they don't respond, and 3 years from now we might all know that a different dosage and schedule would have had a much better chance, but now it's too late because patients develop something equivalent to 'tolerance' to the treatment and next time round it will be less effective.

I wasn't aware of this aspect of rtx treatment - that you only had so many goes with it and then you're done.

Is that the case, @Jonathan Edwards? And if so, is the kind of dosing schedule that F&M are investigating an attempt to deal with this issue?

 

[Kati]

I believe dr Hall is a flat earth believer and that only evidence should be offered to patients, therefore CBT and GET, until there is new evidence. How we get to that evidence is beyond her, she is probably trusting government agencies are prioritizing the research funding, hence the high priorities being HIV, ebola, cancer, diabetes and male pattern baldness amongst the 200 conditions being more important than us.

'Be part of the solution' and don't perpetuate the problem should apply here.

 

[EtherSpin]

I know that in Germany there were 10 CFS patiënts on Rituximab with very bad results one was completely ill and had a wheelchair. He isn't still recovered. No one in this group had a positive effect. So Hariet Hall has a point for warning patiënts. Rituximab isn't going to be a panacea for CFS. Just a very very specific (autoimmune) subgroup will benefit. I think about 20-30%.

do you know any more details about the german group ? like is there anywhere I could read about the dosage and frequency etc ?
regarding subgroups, I do not in any way mean to be disrespectful or dismissive but why would we think that autoimmune/immune dysfunction driven CFS people are a slice as opposed to all of us when we are talking about people who fit the more robust criteria (PEM , memory problems, comprehension and word finding problems, unrefreshing sleep, sensory overload, POTS or less specific OI etc) ? If NK cells being both ineffective and low in number is a common characteristic wouldn't this indicate most of us are this way either because of or VIA a mechanism of a now errant immune system ?
I ask because I want to keep my own expectations firmly in check RE this medication but at the same time I imagined that ritux or related drugs would easily treat more than 20% of us. don't we still have a long way to go with observing the rate and effect of B-cell depletion so a balance can be struck with spacing between infusions, how long a treatment schedule goes for and the actual dosage ?

 

[barbc56]

why would we think that autoimmune/immune dysfunction driven CFS people are a slice as opposed to all of us when we are talking about people who fit the more robust criteria (PEM , memory problems, comprehension and word finding problems, unrefreshing sleep, sensory overload, POTS or less specific OI etc) ? If NK cells being both ineffective and low in number is a common characteristic wouldn't this indicate most of us are this way either because of or VIA a mechanism of a now errant immune system ?

Interesting question. I could be wrong but isn't this issue more complicated than this as our knowledge is limited at this point in time? I think there are often similar symptons but not necessarily the same cause and this makes it difficult to do studies about this. What we do know unfortunately is only the tip of the iceberg.

regarding subgroups, I do not in any way mean to be disrespectful or dismissive

IMHO, you are not being disrespectful. At all! You've asked a legitimate question though I'm not sure what an illegitimate question looks like.

There's the old adage that there are no stupid questions. In fact it's sometimes a great way to frame a post in a less confrontational manner. This doesnt always work and not always possible depending on the question, but it's food for thought when posting.

Barb

 

[EtherSpin]

IMHO, you are not being disrespectful. At all! You've asked a legitimate question though I'm not sure what an illegitimate question looks like.

There's the old adage that there are no stupid questions. In fact it's sometimes a great way to frame a post in a less confrontational manner. This doesnt always work and not always possible depending on the question, but it's food for thought when posting.

Barb

I'm weary of blunt edges no matter the righteousness these days I hate absolute black & white adherence to any viewpoint whether it be ethics, medicine,research,culture - especially having had CFS of a medium level and having known people with it more severe for many more years I am acquainted with lots of facets of human frailty and limitation. I'm at pains to establish basic human respect first and foremost. I've been added to so many snarky online groups (presumptuously,by friends) and I actually have a lot of tolerance for people with polar views to mine,even if the view is silly to me. I never want to be *that* person and having had some episodes in the last 1.5 years of neuroinflammatory mood probs (never before having anything in 30+ years, eternal optimist and cheery bloke) I know that some of us can understandably be deeply upset by something disproportionate.
seriously off topic, someone should swear at me, ask me if I failed to listen in school then ban me from a section of the forum (*standard internet protocols*)

 

[Marky90]

Gijis, it would be nice if you could back up your claims from time to time.

 

[BurnA]

Gijis, it would be nice if you could back up your claims from time to time.

The story of the Germans was brought up on a thread several months ago - probably one of the rituximab threads. It might have originated from a you tube video interview with some German doctors and mikovitis. I can't be sure though. There is a thread about this interview already and be advised that the general consensus is that it contains a lot of nonsense.

 

[Marky90]

So retreatment with rtx seems safe with regards to adverse effects: http://www.rheumatologynews.com/spe...e-in-ra/0273083aacbedfb1f5a6978ccf368b26.html

But, what about efficiancy & tolerance?
Sorry to be a pain in the island of man, but is there any literature on this @Jonathan Edwards ?

 

[Isabelle]

That's quite a leap of judgement. Hall writes an article critiquing a report about Gulf War Syndrome. The report she's reviewing uses Simon Wessley as a citation. Therefore based on this "evidence" we now definitely know that she's made a deal with the devil!

How does that make her colluding with Wesseley? I doubt she is but really don't know one way or another and these situations are usually more complicated than first thought. We certainly can't make any conclusions that she's a sockpuppet of Wessleys using this type of the evidence.

Her blog makes these types of leaps and we jump right on her. But it's okay for us to do this because we are the goodies and Dr. Hall is one of the baddies?

I read her paper and didn't think it was that bad but I need to go through it more throughly. In a sense what she says in the paper, whether pro or con, is only partially pertinent.

When people behave in a way that might come across as knee jerk reactions and jumping to conclusions, and believe me I think her blog was lousy, what does that say about us?

This ultimately backfires and impedes progress. That makes me mad. Why? Because I want to get better and this attitude makes us look like the reputation that people are accusing us of. Lazy, ranting patients who aren't really sick because it's all in their mind and all they need is a bit of exercise and psychological therapy to talk them out of believing they're sick.

Thats not who we are!

We have every right to state our case but we can be adults about it and debate the points the other side is saying without resorting to name calling or jumping to conclusions.

We've been ignored long enough. We have every right to be angry. But we need to be fair and take the high road if we want to see more funding, better studies and not be dismissed as irrational.

I want to get better! But these type of posts, in my opinion, aren't helping us achieve this goal. Some may disagree with that. There are some very good posts on this thread and it would be a shame if they get lost because of a few posts.

Barb

@isabell, I'm not singleing you out here. I was responding to your quote only in the fist paragraph and even with that I was really talking in more general terms. No disrespect intended for for you nor anyone else. I'm just stating my take on things.

With respect Barb you completely misunderstood my point. I wasn’t suggesting she had ‘made a deal with the devil’. I pointed out that she did not reference him directly. I thought her article was quite poor. She said she hadn’t mastered the information in the report yet felt qualified to criticize it.

She said in her article: ‘Skeptics have pointed out that ill-defined syndromes are often reported after wars…’ Who are these ‘Skeptics’ she refers to? Nothing is properly referenced. My background is in science and I consider myself a skeptic, but she isn’t speaking for me. She styles herself as a champion of science-based medicine, yet contradicts the evidence. She has ‘…mixed feelings’ about more money being spent on research (as recommended by the report) to find effective treatments because ‘Research money is short’.

She said ‘ I despair of ever knowing the truth.’ Research is useful in the search for the truth. She mentioned the ‘…overlap with other multisystem illnesses like chronic fatigue syndrome (CFS)…’ I thought this information relevant and pertinent. I thought my response quite measured. I don’t consider it a rant. I made no disparaging remark. I find your attack unwarranted and unjustified.

 

[msf]

I have a Ritux question that I´m sure someone here can answer. Is it possible that the Ritux works by reducing the level of pro-inflammatory cytokines in the body? Is the response to Ritux seen in ME patients consistent with this? Do plasma cells control the level of cytokines indirectly by producing antibodies?

 

[Marky90]

From the phase 2 discussion:

"However, other underlying mechanisms than autoimmunity may explain the observed clinical effects of B-cell depletion on ME/CFS symptom maintenance. Rituximab influences other aspects of immune function than the pronounced effect on CD20 positive B-cells. These include rituximab-induced T-cell inactivation, T-cell polarization to a suppressive phenotype, elimination of B-lymphocytes as antigen-presenting cells, and depletion of a CD20dim T-cell subset [37]. B-cell depletion impairs adaptive and autoreactive CD4-positive cells in mice, as one mechanism for observed clinical benefit of rituximab in presumed T-cell mediated autoimmune diseases [38]. Whatever the mechanism behind the rituximab effect, the patient described in our study with a response but allergic reaction to rituximab, and later treated with the humanized anti-CD20 antibody ofatumumab again achieving a clinical response, indicate B-cell depletion as the factor responsible for response and not some other, unknown effect of the antibody."