My ritux experience so far

[Benji]

I mean I have had great periods, since I startet. December last year was the best I have had for years. When I get better I have my boys more with me. Last desember I spoilt them, took then to cinema, megafun, and brought buddies too. i made them advent-calendar 1 present each day. I told my x to take his girlfriend out because now I was able to have the kids more (he didn’t though, they broke up).
These are things I am dreaming of now, no hope.
I had response for a month ++, and some weeks in may.

 

[Jesse2233]

@Benji the fact that you had that period of much improved health is a great sign. Even if subsequent rituximab infusions aren't the answer it seems that you have promising evidence that autoantibodies are driving some aspect your condition. There are many other treatments to explore

 

[Desertstorm]

Late to this party but any input is very welcome. Here's what they know I have. CFS, FM, autoimmume/systemic body wide inflammation and vasculitis. The inflammation affects skin, pulmonary passages, kidney and eyes. May have missed some! Basically it is classified as Gulf War Illness via VA disability protocol and that it all started in the desert after a bad virus , all sorts of insecticides, military administered anti chem weapon pills (PB) and exposure to a lot of Saddam's nasties. For instance my aircraft had a chem detector installed in the cockpit and registered positive for both sarrin gas and nerve agents three times at altitude.

The fatigue and other symptoms are cyclical in nature but always far worse when tapering off steroids or after an injury or medical procedure. For two decades it was all a matter of functionality until a few yeas ago when I became 60-70 % bed bound and 90% home bound. The next step suggested by my docs is rituxan.


My docs have had me on steroids for many years for the inflammation and tramadol for the pain and sme energy improvement. Steroids suck. So does GWI/CFS.

So reading all I can about rituxan and speaking with the doc there are down sides beyond the cost and if it will work. His plan is to use it to fight the vasculitis and inflamatory aspects and see if that leads to progress in the FM and CFS parts of the puzzle. He uses it often on RA patients. He like all other docs here in MT that I have found do not really get into addressing CFS directly. Certainly the VA medical side does not.

Interesting how this thread evolved and then petered out after the study release. Another dead end or worth pursuing ?

Like I said, looking for opinion and input to help me make a decision. Tried so many other things all I really can hope for now is to be steroid fre and still functional to an extent.

Thanks!

 

[Gingergrrl]

Here's what they know I have. CFS, FM, autoimmume/ systemic body wide inflammation and vasculitis.

@Desertstorm I was just curious, how did your doctor(s) assess and determine that you had autoimmunity and vasculitis?

Interesting how this thread evolved and then petered out after the study release. Another dead end or worth pursuing ?

For me, Rituximab was a game-changer along with IVIG and I am doing the autoimmune protocol and we no longer believe that ME/CFS is my diagnosis. I have multiple auto-antibodies, POTS & Dysautonomia, MCAS, Hashimoto's Disease, and severe breathing and muscle weakness. My treatments have improved everything but the POTS and ability to stand/walk without wheelchair is the most intractable issue (for me).

 

[Jonathan Edwards]

Like I said, looking for opinion and input to help me make a decision. Tried so many other things all I really can hope for now is to be steroid fre and still functional to an extent.

Hi Desertstorm,
I don't post to this forum much any more but I would like to answer here. In case you are not aware, I was the physician who introduced the use of rituximab for rheumatoid arthritis and vasculitis etc. in 1998. I thought the early results in ME/CFS were interesting and my group have worked closely with the Norwegian team but I am now clear that rituximab is not a sensible option for ME/CFS per se. Basically the results show it does not work.

However, rituximab is known to produce good results in various types of vasculitis, including forms affecting kidney and lung. It is a much better option than steroids.

What is not clear to me from your post is exactly what illness you have. If you have vasculitis then that is something quite different from Gulf War illness. The two would not be confused by a competent physician.

So for vasculitis rituximab is good treatment. For ME/CFS it is not. I have no reason to think it is useful for GWI. Vasculitis is not caused by viruses or insecticides or nerve gases as far as I know (except in some very specific infections chiefly in children). Vasculitis can produce severe fatigue. So I think it all depends on whether you have vasculitis. If so the answer is in the textbooks. If not, then rituximab is not something to try without very good reason.

 

[Wonkmonk]

Basically the results show it does not work.

But isn't concluding that it doesn't work after this one negative study just as premature as concluding that it does work after the first positive studies?

And in your opinion - I assume you may have had insight into the study results - is it unreasonable to assume there is a subset of patients for which it actually works? (As I understand Drs Fluge/Mella, they think such a subset may exist)

 

[Jonathan Edwards]

But isn't concluding that it doesn't work after this one negative study just as premature as concluding that it does work after the first positive studies?

And in your opinion - I assume you may have had insight into the study results - is it unreasonable to assume there is a subset of patients for which it actually works? (As I understand Drs Fluge/Mella, they think such a subset may exist)

Nobody as far as I know concluded rituximab was effective after the first trial- certainly not Dr Fluge. There was a suggestion that it might work, despite the primary endpoint not being met. When I reviewed the data in detail I was not convinced that there was the sort of consistent time course that would make one confident of a real effect but I thought it was well worth doing a larger study.

If a large study of this sort comes out negative, as this has, then there is no good justification for pursuing the treatment. There are all sorts of reasons why studies appear positive when there is no effect. There are not many reasons why well designed studies (like those) are negative when in fact there is an effect. The two situations are not comparable.

We know that a small number of people diagnosed with ME turn out to have autoimmune diseases that have been missed and some of these may well respond to rituximab. However, they are a very small number and have specific features of specific conditions so strictly speaking do not have ME. The fact that the phase 3 trial has come out clearly negative means that there is no good justification for thinking that there is an ME responder subgroup.

 

[Learner1]

So for vasculitis rituximab is good treatment. For ME/CFS it is not. I have no reason to think it is useful for GWI. Vasculitis is not caused by viruses or insecticides or nerve gases as far as I know (except in some very specific infections chiefly in children). Vasculitis can produce severe fatigue. So I think it all depends on whether you have vasculitis. If so the answer is in the textbooks. If not, then rituximab is not something to try without very good reason.

Rituximab seems to be being used with some success in patients with autoimmune illnesses. Jarred Younger found that a certain subset of patients have autoimmunity. All patients with ME/CFS don't have the same etiology, lab results, genes, or environmental factors. I.e., we are not generic widgets.

And, ME/CFS is no longer a diagnosis of exclusion. Patients have various comorbidities and drivers of their illness.

The "failure" of the Rituximab trial was sad. I saw somewhere a thoughtful discussion of what the news means, and as @Wonkmonk indicates, the conclusion was that there very well might be a subset of patients for whom it will work.

It may not be a very big subset, and we don't know the characteristics of it yet, but its unlikely it will help absolutely no one ever with ME/CFS.

Of course, we should be looking for other potential solutions, but it sounded like there was still work to be done to better understand the details and ramifications of the Rituximab trials.

 

[Jonathan Edwards]

Rituximab seems to be being used with some success in patients with autoimmune illnesses.

Er, um, yes, it is known to be used with high effectiveness in several autoimmune diseases because of the proof of concept study I published in 2004 in New England Journal of Medicine. Maybe some people have still missed the point that I effectively invented this way of treating autoimmunity. Which is why I not keen to see it used without good reason.

Jarred Younger found that a certain subset of patients have autoimmunity.

I am not aware that Dr Younger has found anything particular that has not been known for yonks - that like healthy people, a proportion of people with ME have autoantibodies. But that means nothing of consequence if we have no reason to think those antibodies are causing the illness - and we don;t so far. I very much doubt Dr Younger would claim he has evidence for that.

The "failure" of the Rituximab trial was sad. I saw somewhere a thoughtful discussion of what the news means, and as @Wonkmonk indicates, the conclusion was that there very well might be a subset of patients for whom it will work.

Well let me just say it plainly. As the guy who invented this treatment and who spent twenty years studying it I can assure pWME that the negative Norwegian study means that we have no reason to think there are any significant subsets of ME that respond to rituximab. Others may well be thoughtful but I have actually been in the middle of rituximab research right from the start and the detailed data from Norway make me pretty sure that there is no 'response' subgroup. There is no consistent pharmacodynamic profile of the sort we saw in RA. There are people who have got better following rituximab but it is unlikely that the drug produced the response. If a trial is negative you cannot conclude that anyone responded, so there is no evidence for a subgroup response.

As I indicated above, there may be a small number of people who have been put under the ME diagnosis who have a responsive autoimmune disease but the way to handle that is to identify the autoimmune disease and treat it.

it sounded like there was still work to be done to better understand the details and ramifications of the Rituximab trials.

As far as I am aware the Norwegians have closed their rituximab programme. I am pretty sure that proposals for work in the UK have been abandoned. I see nothing more we need to understand - the drug was ineffective. There are no ramifications.

Perhaps the most important thing I have learnt from the Norwegian studies is the confirmation that PWME sometimes get dramatically better following treatments for reasons that have nothing to do with the specific treatment. In other words what gets bundled under the general title of 'placebo effect' is not trivial, despite what Dr Knoop and Dr White would have people believe. Maybe something similar to the account Jennifer brea gives in her film of feeling wonderful after starting a treatment, although sadly in that case she crashed again soon after.

 

[Learner1]

If all science were to stop due to old scientists concluding that there was no further work to be done, many significant discoveries would have been overlooked.

Too much is unknown about this disease to pretend that there are black and white answers. Patients are not homogenous, therefore it is unlikely the same tool will or won't cure them all. It's more likely that a toolbox of tools, applied in various combinations, will help us.

If something can cure the autoimmunity that many of us have, it would be useful. Particularly as some of us have underactive immune systems as well, making use of immunosuppressants a bad idea. I am not a fan of immunosuppressants as I met too many patients who had been on them who got cancer. But my autoimmune symptoms are my most disabling.

Perhaps Rituximab is not the optimal choice - maybe there's something that will work better. But it obviously works on some patients, or it wouldn't be used as widely as it is. I know 3 patients who've had success with it in their unique situations.

I'd like to learn more.

 

[Wonkmonk]

As far as I am aware the Norwegians have closed their rituximab programme. I am pretty sure that proposals for work in the UK have been abandoned. I see nothing more we need to understand - the drug was ineffective. There are no ramifications.

Please let me point out that I generally share your scepticism, because the time-response patterns in the positive first trials was quite strange and couldn't be explained. And - more importantly - hundreds if not thousands of patients have been treated at OMI and Kolibri with Rituximab. If Rituximab cured even only a small percentage of them, I am wondering, where are they?

But it still sounds premature to categorically rule out that there is a subset of responders.

I'm sure you have much better insights than I have, but I have found this lecture from just a month ago (which luckily has subtitles) from Dr Mella in which at 24:10 he talks about Rituximab and says he thinks there is a subset who respond, so I would be surprised if they stopped all further investigation. Quoting the subtitles:

"Then one might ask, does this mean the end of Rituximab in connection with ME? I'm not so sure about that. But I think in order to use it in further studies, we need some marker to tell us which patients benefit from it. Based on what we have seen from the patients, I still think there is a subgroup that has an effect. However, we can't identify them today through clinical data."

 

[Frenchguy]

Perhaps the most important thing I have learnt from the Norwegian studies is the confirmation that PWME sometimes get dramatically better following treatments for reasons that have nothing to do with the specific treatment. In other words what gets bundled under the general title of 'placebo effect' is not trivial, despite what Dr Knoop and Dr White would have people believe. Maybe something similar to the account Jennifer brea gives in her film of feeling wonderful after starting a treatment, although sadly in that case she crashed again soon after.

Maybe "placebo responders" don't have ME, maybe Jennifer Brea don't have ME and have a very severe POTS case. No one know.

Unfortunately, there is currently no test to confirm that.

The fact that Mark Davis found T cell expansion (probably in a subgroup) and preliminary results of cyclo trial could help to understand if response is real or placebo in this subgroup.

 

[Gingergrrl]

Maybe "placebo responders" don't have ME, maybe Jennifer Brea don't have ME and have a very severe POTS case. No one know.

I agree that no one knows but from having severe POTS myself, when I watched Unrest, I did not identify with Jennifer's daily experience b/c she could do things that I still cannot dream of doing (POTS-wise) and my POTS is better now. But her daily experience was different than mine. Am not diagnosing her (or even myself!) and just reporting my experience.

Maybe the responders to Ritux have a specific autoimmunity (like me) that has yet to be given a name. Maybe we are the "misdiagnosed subgroup" or maybe there are some with true ME/CFS and autoimmunity and the Ritux is treating the autoimmune component (in that particular group) which still leads to an overall improvement. Just my thoughts on it.

 

[Jonathan Edwards]

"Then one might ask, does this mean the end of Rituximab in connection with ME? I'm not so sure about that. But I think in order to use it in further studies, we need some marker to tell us which patients benefit from it. Based on what we have seen from the patients, I still think there is a subgroup that has an effect. However, we can't identify them today through clinical data."

As I have said before, I think Dr Mella is trying to let people down gently. Maybe he believes that there is a subgroup that responds but the evidence does not indicate that. I have followed responses in a dozen different diseases. I have seen where there is a biological effect with a consistent pharmacodynamic profile, that is supported by controlled trial evidence. I have seen where there is no consistent profile and no consistent trial evidence. The situation in ME is clear - there is no reliable evidence for a significant biological effect. There is no consistent pharmacodynamic profile. I am as disappointed as anyone but the balance of evidence is no effect.

My main concern, where Dr Mella would agree with me 100% is that I do not want private physicians in the US or Australia or Scandinavia or wherever, who know little or nothing of B cell biology, tinkering around with rituximab and ending up with situations like Whitney Dafoe and Mr Bodden. OK we have all heard of three people who seem to have got marvellously better but we have also all heard of at least two who have got very seriously worse - for whatever reason. That does not look like a profile for a worthwhile drug. I think it is unethical to use rituximab in ME outside a formal trial at present. I am prepared to put that out publicly and to repeat that statement in a court of law if anything were to go wrong and my opinion be asked.

 

[Frenchguy]

Maybe the responders to Ritux have a specific autoimmunity (like me) that has yet to be given a name. Maybe we are the "misdiagnosed subgroup" or maybe there are some with true ME/CFS and autoimmunity and the Ritux is treating the autoimmune component (in that particular group) which still leads to an overall improvement. Just my thoughts on it.

+1

But I agree with Prof Edwards that people can have true undiagnosed autoimmune disease.
There is hundreds autoimmune disease, and people can have one without tradionnal markers or blood abnormalities, and without tradionnal symptoms !
Is ME an novel model of autoimmune disease ?
Very confusing ... Fluge & Mella said that there patients have increased family members with autoimmune conditions and genetic suceptibility.
There is a genetic predisposition to have ME.

The current results show that the core problem is in the blood and that people improve with general immunosuppresion, this is a good news.

I want to cry when I see $$$ invested to support the psychological research in this disease.

 

[Gingergrrl]

I think it is unethical to use rituximab in ME outside a formal trial at present. I am prepared to put that out publicly and to repeat that statement in a court of law if anything were to go wrong and my opinion be asked.

You have said it publicly over and over again and to be honest, it is getting tiring. I have no idea who you are threatening in a court of law but if you are referring to my TWO doctors, who independently of each other feel Ritux is the right treatment for me, I think they can more than hold their own in court. They have given me enough life back to help my mom while she is dying. They are the mavericks of this world and they are my heroes.

 

[Wonkmonk]

@Jonathan Edwards Thank you for sharing your thoughts, as I said, I am also sceptical, although as probably all CFS patients I tend to desperately look for the next straw to grab and after the hype we've seen, it is hard to let Rituximab go, and I can understand patients who - despite the advice not to try it - ultimately decide to grab that straw.

May I perhaps ask you about your opinion about Cyclophosphamide as a possible treatment option? Dr Mella appears to be much more optimistic about this drug. Again quoting the subtitles from the video above:

"The Cyclo-Study where we used Cyclophosphamide has preliminary very good data. Many patients are reporting improvement, but the problem is that it is less well tolerated than Rituximab. Particularly subjective, nausea is a significant problem and we are a little unclear about what to do next. When we look at the Rituximab data, we see that in order to be certain what effects we are really looking at, then we need to do a form of double blind study, at least a study that can say something about that are in operation in the study. So we are thinking about making a double blind study on Cyclophosphamide. It is difficult because the substance causes nausea. Even if we give a lot of anti-nausea medication, there are some patients who become nauseous and there is more nausea among ME patients than in cancer patients. This is a treatment we provide daily at the cancer ward. Cancer patients rarely get nauseous when they get the anti-nausea medication, whereas ME patients in fact do. So the tolerance is worse in ME patients than in cancer patients. So we are currently in the thinking stage when it comes to Cyclophosphamide. But we must remind ourselves that when we had the first patient observations, it was with chemotherapy that contained either ifosfamide or Cyclophosphamide. It might be that the nonspecific immunosuppression cyclophosphamide provides may become a therapeutic offer for patients in the future."

 

[Hip]

You have said it publicly over and over again and to be honest, it is getting tiring.

It is important to bring up the serious side effects and safety issues of a drug. It would be unethical not to, and it's not something that should be considered "tiring". You would not call FDA Black Box warnings tiring; everyone needs to be aware of the risks.

Even out of the ME/CFS 20 patients on this forum whose rituximab treatment I followed, 5 of these patients had serious or nasty side effects, including one 26 year old who developed multiple bacterial lungs infections that required lung surgery to remove, leaving many scars on the chest, as well as a heart ejection fraction down to 45%.

And out of these 20 patients, only two made improvements: one did really well, but had other health conditions that might explain why the rituximab worked; the other made good but not spectacular improvements.

my TWO doctors, who independently of each other feel Ritux is the right treatment for me

Very pleased that the rituximab treatment had such positive effects for you, and that you had no adverse effects.

Though as you don't have ME/CFS by any of the established definitions of this disease, it does not really throw much light on the efficacy of rituximab for ME/CFS, and the risk / benefit considerations of rituximab in the case ME/CFS.

As I understand it, the issue here is the risks involved, and whether the benefits (which we know are infrequent) balance out those risks. I am sure if you spoke to ME/CFS patients who have had severe adverse effects, they would have their own opinions about the risk / benefit ratio.

 

[Gingergrrl]

Though as you don't have ME/CFS by any of the established definitions of this disease, it does not really throw much light on the efficacy of rituximab for ME/CFS, and the risk / benefit considerations of rituximab in the case ME/CFS.

But 90% of American doctors to this day (2018) still label me with a "CFS" diagnosis. And it is not just me. There is clearly a misdiagnosed group, some severely ill like I was, who are labeled with CFS and basically told to fuck off and die by the traditional medical establishment in the US (so I can only imagine what is happening in other countries).

We have an illness yet to be formally named and it usually involves having multiple autoantibodies. The volume of PM's that I was receiving from people similar to me was insane and every last one had been given a "CFS" diagnosis by at least one doctor (and usually multiple doctors).

I am sure if you spoke to ME/CFS patients who have had severe adverse effects, they would have their own opinions about the risk / benefit ratio.

I have spoken to them and don't know why you would assume otherwise? I spoke to hundreds of Rituximab patients as part of my research. Some from OMI, some from Center for Complex Diseases, some from Kolibri, and many with private doctors across not just the US but worldwide. Many from PR, some from Facebook, some from other medical groups. Almost every single one had been given a "CFS" diagnosis as I was.

I continued to dig deeper since 2013 and with each layer, it brought me to my current treatment. I do not deny or sugar coat that there can be major risks like anaphylaxis or very rarely PML. It also should not be done if you are at risk of reactivating hepatitis or TB (which I was not b/c never had either).

But if I were to name the top 100 things that have injured or harmed me in my pursuit to get better, Ritux would not even make the list (for me).

 

[Hip]

But 90% of American doctors to this day (2018) still label me with a "CFS" diagnosis.

Most doctors throughout the world I think are very badly trained when it comes to ME/CFS diagnosis, and probably have never heard of the exacting Canadian consensus criteria. I would think in the mind of many doctors, ME/CFS is just a vague waste-bin diagnosis that they conveniently use when nothing else fits.

So these doctors may well have placed you in their illness waste-bin, but they shouldn't be doing that really. It gets them off the hook by calling it ME/CFS, and it gets you out of their office; but really they should be investigating your case further, and getting to the bottom of it.

If I remember rightly, a few years ago I think it was the NIH that set up a department for dealing with mystery illnesses that no other doctors or specialists could fathom. I can't remember the name of it, but that's ideally how patients should be treated when their symptoms match no known disease: they should be investigated by some very high level researchers.

We have an illness yet to be formally named and it usually involves having multiple autoantibodies. The volume of PM's that I was receiving from people similar to me was insane and every last one had been given a "CFS" diagnosis by at least one doctor (and usually multiple doctors).

Did those other people you were in contact with have a symptomatically identical condition to you, or did they each have their own idiosyncratic symptoms which just happened to be labelled as ME/CFS?

I am just wondering if you might have a new unknown syndrome that others also have.

I do not deny or sugar coat that there can be major risks like anaphylaxis or very rarely PML.

Those are the standard rituximab risks for all patients, but in the case of ME/CFS, we know that there is also an additional risk of severely worsening ME/CFS, as in the cases of Whitney Dafoe and Olaf Bodden, and possibly others that we are not aware of.

So it's these considerations of how much risk is involved, weighed up against the chances of improvement (which are poor in the case of ME/CFS).

But if I were to name the top 100 things that have injured or harmed me in my pursuit to get better, Ritux would not even make the list (for me).

That's great that you fared so well, though one cannot judge the safety of a drug via the effects of only one patient, and you may be the only patient with your mystery condition that's ever been treated with rituximab.