Experience with Rituximab

[Insomniac]

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A patient with CFS/ME happened to get cancer and by chance was given Rituximab as treatment for cancer and CFS symptoms went away.

The patient was able to continue Rituximab after the cancer was gone and has received Rituximab for over 4 years in various doses.

 

[junkcrap50]

You should try posting your request at www.s4me.info . There might be someone over there who does.

 

[Gingergrrl]

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That is really interesting and thank you for sharing it. I am still of the belief that there is a group of people who were diagnosed with ME/CFS (or just "CFS" in the US) who are responders to Rituximab. I am not certain if these individuals are an autoimmune sub-group, misdiagnosed, or some of each.

I also believe (as do others that I have spoken to) that there was a major flaw between the Phase 2 and Phase 3 Rituximab Trials b/c different doses of the medication were given. In Phase 2, everyone received One Gram (1000 mg) per infusion which is adequate to cover all patients using the BSA (body surface area) formula for autoimmune dosing.

However, in Phase 3, patients were given the first two doses per the BSA formula (which means different subjects got different doses) and then for all of the remaining infusions in the trial, each subject only got 500 mg (which is not adequate to cover all patients, especially men or people who are very tall or overweight). My own dose for Rituximab is 600 mg per infusion (based on the BSA formula) so I know that 500 mg is a very low dose. This is why it makes sense that were responders in Phase 2 (who received 1000 mg) but not in Phase 3 when the dose was literally cut in half to 500 mg. I would LOVE to hear what such a patient thinks about this dosing issue (since I have no science background but this seemed to me that it would make the trial invalid or at least very questionable).

Do you know what the dose was for each infusion? I do not know how it doses for cancer (only for autoimmunity) and was wondering if the dose changed from when doing it specifically for cancer vs. at present?

I was incredibly lucky to have found two doctors who take me seriously (without me having a science background). Even though I did not do Ritux with an ME/CFS diagnosis, I did do it off-label and none of the three diagnoses that I have are FDA approved for Ritux so I am in a similar boat. I have proven autoimmunity but not a diagnosis that Ritux is currently approved for.

This is also extremely helpful to hear b/c I am currently well into my second year of Ritux and my next infusion will be on 5/3. In my case, every single infusion has been 600 mg and that has never wavered. Vs. after the first six infusions (which took exactly one year), we have stretched out the interval between infusions from 3-months, to 4-months, and now to 5-months. So I will be getting a total of two infusions this year (2019) vs. six infusions over the one year period that I started (July 2017 to July 2018). This upcoming infusion will be #8 total (or my 2nd maintenance infusion).

My doctor 100% believes that it is the Rituximab alone that is maintaining my remission and I agree. I also did two years of high dose IVIG (which brought some symptoms into remission prior to ever starting Ritux) but the most intractable of my symptoms did not go into remission until about nine months into Ritux and they have not returned. My last IVIG was July 2018 (almost one year ago) so any affect from that is long gone vs. my B-cells remain at zero from Ritux (actually I am waiting for my most recent lab results but am almost certain that once we get them back, any day now, that they will show that my B-cells are still at zero).

I had wondered if some patients really stayed on Rituximab long-term and maintained their remission? But this patient is solid evidence that this can happen since she is still in remission after four years and is even working again! This made me so happy to hear!

I was also curious how the doctor decided to keep a 3-month interval for maintenance infusions? Do you know if they tried to stretch out the interval between infusions but the symptoms returned? No worries if you do not know any of these answers (and this is a topic of great interest to me if you can't tell )

I'm tagging a few people who possibly might find your post interesting @Blake2e @Learner1 @ClaireKnowles

 

[RL_sparky]

PMed contact info.

 

[Murph]

full contact details here:

https://www.uib.no/en/persons/Olav.Mella

https://www.uib.no/en/persons/Øystein.Fluge

 

[Insomniac]

Thank You Murph

 

[Hip]

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It would be interesting if the patient has any insight into the specific nature of his/her ME/CFS. Or whether he/she she might not have ME/CFS, but a similar disease to ME/CFS that also causes fatigue.

Generally rituximab has been a failure as an ME/CFS treatment. In fact the phase III trial showed that patients given rituximab actually did worse than the controls who were not given this treatment, that's how bad the result was.


But if rituximab does work in a small subset of patients with ME/CFS or ME/CFS-like symptoms, it would be good to identify what sort of disease this subset actually have. It may or may not be ME/CFS.

 

[Gingergrrl]

Generally rituximab has been a failure as an ME/CFS treatment. In fact the phase III trial showed that patients given rituximab actually did worse than the controls who were not given this treatment, that's how bad the result was.

I completely agree with you @Hip that the Phase 3 trial results were a failure but I am curious what you think of the DOSE of Rituximab in Phase 3 being 500 mg vs. 1000 mg in Phase 2 (literally 50% reduction) and what I wrote in post #3 of this thread. How is this factor being dismissed?

But if rituximab does work in a small subset of patients with ME/CFS-like symptoms, it would be good to identify what sort of disease this subset actually have. It may not be ME/CFS.

I totally agree and there is a sub-set of people who have improved with Rituximab who have an ME/CFS diagnosis. What we do not know is if they are a true autoimmune sub-set or a misdiagnosed group? I've seen statistics that at least 30% of people with ME/CFS are misdiagnosed (like I was).

In Jan 2013, my illness started with a post-viral syndrome that met CFS criteria in the US at that time (and followed Mono/EBV), and I was told by every doctor I saw that I had "CFS". This included PCP (GP), an Endocrinologist, a Psychiatrist, a Naturopath, and Cardiologist. If I had not found Phoenix Rising (which is how I found my doctor), I don't even know if I would be alive right now, and I certainly would not be walking without a wheelchair again, (no matter what label is given to me) and the labels for my illness from 2013 to 2019 have been pages long! My illness did not begin as autoimmune and shifted from viral to autoimmune later in it's course.

 

[Hip]

DOSE of Rituximab in Phase 3 being 500 mg vs. 1000 mg in Phase 2 (literally 50% reduction) and what I wrote in post #3 of this thread.

I don't think the dose was 500 mg, but around 865 mg, according to my calc below. The phase III study says:

Treatment induction with 2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months

The average body surface area in Europe is 1.73 square meters, so that means the average patient in the phase III trial would be getting a rituximab dose of 500 X 1.73 = 865 mg. So that just slightly less than 1000 mg. I don't think it would make much difference.

In any case, I remember Prof Edwards saying that the same therapeutic effect can probably be achieved using one tenth of the normal rituximab dose. Drug companies selling rituximab just err on the side of caution and provide high doses.

I was told by every doctor I saw that I had "CFS".

If I remember rightly from a previous discussion, your symptoms would not be diagnosed as ME/CFS by any of the ME/CFS criteria, even the looser criteria like the CDC Fukuda. So whatever you disease you may have, although it seems to have responded well to rituximab, it's not ME/CFS by the standard criteria.


IN general ME/CFS patients on this forum have done very poorly on rituximab, echoing Fluge and Mella's negative results.

Some years ago I went through every single rituximab account on this forum I could find, and out of 22 ME/CFS patients trying rituximab on Phoenix Rising, only 2 of them responded: Rebecca2z responded well, funkyqueen less so.

Rebecca2z also had no less than four autoimmune diseases, so it's likely the benefits she experienced from rituximab were connected to her autoimmunity. Thus we can probably discount her case.

So out of 22 ME/CFS patient trying rituximab on Phoenix Rising, only 1 patient experienced some modest improvements on rituximab. A pretty dismal success rate, but one in keeping with the negative F&M phase III result.

For the rest of the 22 there were no long-term improvements. And 5 out of the 22 trying rituximab experienced serious side effects.

So sadly rituximab turned out not to be the savior of ME/CFS patients as everyone had hoped for. But it does seem that you do get a few people with ME/CFS symptoms responding. Whether those patients have ME/CFS, or some unusual subset of ME/CFS, or a different disease which has ME/CFS-like symptoms, I don't think anyone knows.

 

[Mel9]

Rachel, I really hope that your friend is able to reach Dr. Fluge. I was just curious, could she also try to contact Dr. Mella?



I completely agree with you @Hip that the Phase 3 trial results were a failure but I am curious what you think of the DOSE of Rituximab in Phase 3 being 500 mg vs. 1000 mg in Phase 2 (literally 50% reduction) and what I wrote in post #3 of this thread. How is this factor being dismissed?



I totally agree and there is a sub-set of people who have improved with Rituximab who have an ME/CFS diagnosis. What we do not know is if they are a true autoimmune sub-set or a misdiagnosed group? I've seen statistics that at least 30% of people with ME/CFS are misdiagnosed (like I was).

In Jan 2013, my illness started with a post-viral syndrome that met CFS criteria in the US at that time (and followed Mono/EBV), and I was told by every doctor I saw that I had "CFS". This included PCP (GP), an Endocrinologist, a Psychiatrist, a Naturopath, and Cardiologist. If I had not found Phoenix Rising (which is how I found my doctor), I don't even know if I would be alive right now, and I certainly would not be walking without a wheelchair again, (no matter what label is given to me) and the labels for my illness from 2013 to 2019 have been pages long! My illness did not begin as autoimmune and shifted from viral to autoimmune later in it's course.

Your story is inspirational @Gingergrrl
You show that Intelligent patients might help solve this horrible disease.

 

[junkcrap50]

You may try contacting @Cort who may have direct contact means for Fluge & Mella. Also, he may write an article about this patient.

 

[Gingergrrl]

@Hip I want to try to explain my points better b/c after reading your reply, I don't think I explained them well. I really value your opinion and the open discussion that we are allowed to have here on PR.

I don't think the dose was 500 mg, but around 865 mg, according to my calc below. The phase III study says:

In regard to the issue of dosing, I am going to quote exactly what you said in your post above and the bolding is mine:

Treatment induction with 2 infusions of rituximab, 500 mg/m2 of body surface area, 2 weeks apart, followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9, and 12 months

The first TWO infusions in Phase 3 of the trial used the BSA (body surface area) formula which is used in the Autoimmune Protocol for Rituximab. This means that for the first two infusions, patients received doses that were specific for their own BSA and very well could have averaged 865 mg as you stated. However, for the four additional infusions in Phase 3 of the trial, every patient received a fixed dose of 500 mg.

Not only is this a dose that is lower than the average BSA dose that you calculated of 865 mg, what is more important is that it is literally HALF the dose that each subject received in Phase 2 of the trial. In Phase 2 of the trial (which had several responders who ALL met full criteria for ME/CFS), every single patient received 1000 mg of Rituximab for every single infusion. This is a high enough dose to capture those who had a high BSA.

In addition, there were several responders to that dose. From the perspective of consistency for the trial, if you had several responders in Phase 2 (who all met criteria for ME/CFS), but then you literally cut the dose in half for four of the infusions for Phase 3, you are no longer running the same trial. How is this not a confounding variable that would mess up the results? I literally cannot figure this out!

The average body surface area in Europe is 1.73 square meters, so that means the average patient in the phase III trial would be getting a rituximab dose of 500 X 1.73 = 865 mg. So that just slightly less than 1000 mg. I don't think it would make much difference.

According to my own two doctors, my infusion center nurses, and the pharmacists at my infusion center (who administer Rituximab on a daily basis for cancer and autoimmunity), there would NOT a big difference between 865 mg and 1000 mg BUT there would be a big difference between 500 mg and 1000 mg because 500 mg would NOT be enough to safely assume that all B cells had been killed. I am not a large person and my dose using the BSA formula is 600 mg. So 500 mg would be too small of a dose even for me, let alone someone who is taller or weighs more than me.

In any case, I remember Prof Edwards saying that the same therapeutic effect can probably be achieved using one tenth of the normal rituximab dose. Drug companies selling rituximab just err on the side of caution and provide high doses.

According to everyone I listed above (doctors, infusion center nurses, pharmacists) a dosage of 1/10th of Rituximab would not be therapeutic b/c it would not kill all B cells. And insurance companies (at least in the US) are the opposite of what you described above and would do anything humanly possible to only have to pay for the lowest dose that they can get away with. No insurance company is going to pay for a higher dose if they can pay for a lower dose. We had to calculate the BSA formula for autoimmunity using my height and weight and that is what we got.

If I remember rightly from a previous discussion, your symptoms would not be diagnosed as ME/CFS by any of the ME/CFS criteria, even the looser criteria like the CDC Fukuda. So whatever you disease you may have, although it seems to have responded well to rituximab, it's not ME/CFS by the standard criteria.

I think you are missing my point which is that I was diagnosed with "CFS" in the US in 2013 & 2014 by literally endless doctors, of various disciplines, who were well educated and respected but my current doctor and I now believe that every single one of them was wrong. My point is that the rate of misdiagnosis is extremely high (possibly 30% to 40% of all CFS diagnoses are incorrect). Yet I had no prior knowledge of CFS so when multiple doctors told me that it was my diagnosis, I assumed that they were correct and it is why I searched on-line and found PR and decided to join to learn more about my diagnosis.

I was very lucky that I had the family support and financial means to travel to see doctors and get testing in 2016 that allowed us to discover that I had several obscure autoantibodies. But it was finding Phoenix Rising in 2014 that led me to my doctor (and how many people never find PR)? I literally did research 24/7 (and found people much smarter than I will ever be!) to help me figure this out. It became my full time job b/c my lungs were so weak, I had one doctor tell me that if it did not plateau, I could end up on a ventilator.

If I had not done all of this and just accepted that every single doctor told me that I had "CFS" and that there was "no treatment" I might be dead right now (from the progressive muscle weakness or from an episode of anaphylaxis or God knows what). There is zero chance that I would have gotten IVIG and Rituximab with an ME/CFS diagnosis which is my entire point.

But to your first point, when I got sick in Jan 2013, I had a post-viral fatigue syndrome (post Mono-EBV) that to 99% of US doctors was "CFS". I had unrelenting fatigue where I could not get out of bed to take a shower. It felt like the Mono had re-activated and I had flu-like symptoms, muscle pain, severe insomnia, headaches, nausea, and within two weeks of it starting, I developed severe POTS with my HR in the 160's and 170's. It was the POTS (even though I didn't know the word "POTS" yet) that told me that something was VERY wrong. Every doctor I saw ruled out depression and the only label they could give me was "CFS" (because "ME" is not used in the US). This is random but even Dr. Chia (who I saw in person) told me that I had ME/CFS but that he had no treatments to offer me.

By the time I found Phoenix Rising in mid 2014, my illness had completely shifted and the core symptoms were POTS & Dysautonomia plus the progressive muscle and lung weakness (and then by 2015, the MCAS and allergic reactions). The more I read on PR, the more I was convinced that I had a different illness (in spite of the overlap with POTS & MCAS) and in spite of multiple people (at that time) trying to convince me that I was wrong and to stop searching "b/c I had CFS".

My point is that my illness started the same (with re-activated elevated EBV titers, very low NK functioning, etc) but then shifted into a completely different entity. How many people do not have the opportunity to see the doctors that I did and are left with a "CFS" diagnosis that is possibly not correct?

IN general ME/CFS patients on this forum have done very poorly on rituximab, echoing Fluge and Mella's negative results.

Echoing results of the Phase 3 trial but not of the Phase 2 trial. There were many responders in Phase 2 of the trial (in which the higher dose of Rituximab was used). And all of those subjects had a solid ME/CFS diagnosis. Unless some of them actually were misdiagnosed and had an unknown autoimmune disease like I did? From Phase 2, there were true responders and either they are an autoimmune sub-group or they were misdiagnosed. Why are those people being discounted (I do not mean by you, I just mean in general). I think we can learn a lot from them but sadly Phase 3 cut the dose in half (to 500 mg) for four of the six infusions. It even cut the loading dose (the two initial infusions) although not by half.

I also disagree that no one from PR has had positive results from Rituximab even if you discount Rebecca2z who is a friend of mine (Edited to add: my point is not that she is a friend vs. that she was diagnosed with "CFS" by both UCLA and Stanford. This in no way means that her "CFS" diagnosis is correct, vs. that she believed it to be correct, as did I re: my own case at that time). There are people I don't have permission to name, so I have to respect that, but of those who currently post, right off the top of my head I can think of Blake2e, ClaireKnowles, and Pogoman (and I am sure that there are others that I am forgetting) plus this patient and several people in FB groups that I belong to who were initially diagnosed with ME/CFS (but it is unclear, even to them, if it is their correct diagnosis).

So sadly rituximab turned out not to be the savior of ME/CFS patients as everyone had hoped for. But it does seem that you do get a few people with ME/CFS symptoms responding. Whether those patients have ME/CFS, or some unusual subset of ME/CFS, or a different disease which has ME/CFS-like symptoms, I don't think anyone knows.

I absolutely agree with you that Rituximab is not the savior of the ME/CFS community and I don't believe it is the savior of any community. Ritux is FDA approved for RA yet a huge percentage of RA patients will not be responders. No one can predict who will be a responder in advance. However, if I had started to respond and then we suddenly cut my dose from 600 mg to 300 mg and I stopped responding, I would assume it was to the 50% cut in my dose vs. another factor (like in Phase 2 to Phase 3 of the trial).

And I agree with what you said that we do not know if there is an unusual sub-set of responders or if there are multiple diseases with overlapping symptoms. I am not talking about myself vs. in general. I have had the opportunity to truly get to know hundreds of people since joining PR in 2014 and there are people who had rock solid "CFS" diagnoses who later turned out to have other illnesses (from mitochondrial disease to myasthenia gravis to Lupus to autoimmune encephalitis, etc).

Your story is inspirational @Gingergrrl You show that Intelligent patients might help solve this horrible disease.

Thanks, Mel, and that is very sweet of you! But I am not looking for compliments and my point (that I am still not sure if I expressed well !) is not about me vs. that there are responders to Rituximab and this trial (in my opinion) did not help to identify who they are. I still believe Rituximab is an effective choice for a small sub-group of people, and even if they are a mis-diagnosed group, it would be incredibly helpful to figure this out so that they can get the proper treatment AND to get those people out of ME/CFS studies so they don't confuse the results. (Sorry that was not directed at you, Mel, just the first sentence where I quoted you).

 

[IThinkImTurningJapanese]

Some years ago I went through every single rituximab account on this forum I could find, and out of 22 ME/CFS patients trying rituximab on Phoenix Rising, only 2 of them responded: Rebecca2z responded well, funkyqueen less so.

You missed one,
@Butydoc

Hi Gingergrrl,

I do believe your post are important, but I understand your position. I will add some of my experience concerning retuximab. I'm almost at the 6mo mark and starting to see some improvement. I have received 1000mg each dose.

 

[Hip]

From the perspective of consistency for the trial, if you had several responders in Phase 2 (who all met criteria for ME/CFS), but then you literally cut the dose in half for four of the infusions for Phase 3, you are no longer running the same trial. How is this not a confounding variable that would mess up the results? I literally cannot figure this out!

I've not looked at the Fluge and Mella studies in any detail (I find reading long articles or studies difficult). But I have just had a quick read, and it seems that much more rituximab was given to patients in the negative 2019 phase III study, compared to the positive 2011 phase II study.

The only 2 double-blinded, placebo controlled rituximab trials that F&M performed were:

➤ The 2011 phase II study on 15 ME/CFS patients given rituximab, and another 15 given a placebo. Those given rituximab had their disease for 1 to 13 years, and satisfied the Canadian consensus criteria. The 30 patient cohort was followed up for at least 12 months in this study.​

​

In this study, only two rituximab infusions of 500 mg/m2 were given (two weeks apart), but with no further follow-up infusions. The B-cells were greatly depleted by these infusions (see this graph), but then B-cell numbers gradually started to recover at about the 6 month stage after the infusions (as no further top-up infusions were given to keep B-cells down).​

​

Phase II response rate: 67% in the rituximab group, and 13% in the placebo group.​

​

​

➤ The 2019 phase III study on 151 ME/CFS patients (split into either receiving rituximab or placebo) who had their disease for 2 to 15 years, and satisfied the Canadian consensus criteria. In this study, two rituximab infusions of 500 mg/m2 were given (two weeks apart), followed by 4 maintenance infusions with a fixed dose of 500 mg at 3, 6, 9 and 12 months.​

​

Phase III response rate: 26% in the rituximab group, and 35% in the placebo group.​

So the difference between the phase II and III studies is that the phase III study gave two initial doses plus top-up maintenance doses of rituximab throughout the year, but the phase II study did not provide any maintenance doses, only the two initial doses.

So in spite of administering more rituximab, the phase III study got much worse results.

Obviously with its much larger cohort, the phase III study is considered statistically more reliable than the phase II study.

The phase II study may have just been a statistical blip, with its apparent success just a spurious result.

Or the perhaps the phase II study might have included different types of ME/CFS patient, and that's why the results were different. F&M did not test the patients for which infections they had, and given that there was an 8 year difference between the publication of these studies, perhaps there may have been an outbreak of a different virus by the time the phase III study was conducted. So the phase III study might have been treating a different viral subset.

There was an outbreak of giardiasis-caused ME/CFS in Bergen, Norway in 2004, which is where Fluge and Mella conducted their phase II rituximab trial. This is an unusual form of ME/CFS, and maybe there were lots of patients in their phase II trial who had this Giardia lamblia form of ME/CFS.

The phase III trial was a multi-center trial, so would not have had may of these Giardia lamblia m, patients.

Or maybe even the fact that the phase III study used much more rituximab might have been a factor. Perhaps more is not necessarily better with rituximab, when it comes to treating ME/CFS.



F&M also conducted an 2015 unblinded study on 29 ME/CFS patients, with no placebo group. In this the provided two initial infusions of rituximab 500 mg/m2 two weeks apart, followed by maintenance rituximab infusions of 500 mg/m2 after 3, 6, 10 and 15 months, and with follow-up for 36 months. The response rate was 64%, but without a placebo group, that result is not really that useful.

My point is that the rate of misdiagnosis is extremely high (possibly 30% to 40% of all CFS diagnoses are incorrect).

Yes, chronic diseases are quite often misdiagnosed initially, often not because of any negligence on the part of doctors, but because diagnosis is hard. It often takes a few years to settle onto the correct diagnosis, because it may take a year or two to perform all tests necessary to check for the various diseases that can have similar symptoms.

Another reason why chronic diseases are liable to initial misdiagnosis is because most chronic diseases start slowly, with minimal symptoms to begin with, and the symptoms gradually get worse over the years. So when a patient first goes to the doctor, the symptoms may still be quite minimal and subtle. That makes it harder to figure out what disease they might have. But say 5 years down the line, those subtle symptoms may become more severe and thus more obvious and apparent, making diagnosis easier.

So in the early stages of chronic disease, misdiagnosis is common. But eventually doctors tend to figure out the correct diagnosis.

In Fluge and Mella's phase III trial, they used Canadian consensus criteria, and only included patients that had had the disease for 2 to 15 years. So it's likely that most of the cohort were ME/CFS patients.

I think that even in the early stage, had your doctors strictly followed the CCC, they probably would not have diagnosed you with ME/CFS.

I can think of Blake2e, ClaireKnowles, and Pogoman (and I am sure that there are others that I am forgetting)

The first two are in my list, but it's too early to see their results (you need to wait at least around 12 months or so). Pogoman I did not know about, but I've added him to my list — thanks. Also too early to tell in his case.

In the 2015 paper, F&M found for major responders, the mean time from the first rituximab infusion until start of clinical response was 23 weeks (range 8-66 weeks).

You missed one,
@Butydoc

Butydoc is on my list, but I've seen no reports of long term success. Some patients on this forum reported an initial improvement, but nothing that panned out long term. That's why it important to wait at least 12 months after the rituximab therapy starts to get the final verdict from each patient.

Quite a few patients on my list had rituximab back in around 2013.

 

[Rufous McKinney]

My illness did not begin as autoimmune and shifted from viral to autoimmune later in it's course.

So: what do you consider to be your diagnosis:? If you care to share..... I'm glad to find this discussion as I was curious regarding your positive experience @Gingergrrl , while the study came back: Rituximab didn't help.

CFS just seems to remain the easy catchall term that isn't conveying much of whats actually going on.

and its just flummuxing, to me (how do you spell that?) , how hard it is to get anywhere in a conversation with care providers.

 

[Rufous McKinney]

That's why it important to wait at least 12 months after the rituximab therapy starts to get the final verdict from each patient

It took ten months for Chinese herbs to clear a severe inflammatory rash I had covering 1/4 of my body surface.

the regular doctor recommended I cover 1/4 of my body in cortisone creams. Right? I don't think so.

There was no placebo effect. I gave up , figured the rash wasn't going anywhere, but continued the herbs because they helped me feel better and gain energy.

so: it can take quite a while to correct these things.

 

[Hip]

It took ten months for Chinese herbs to clear a severe inflammatory rash I had covering 1/4 of my body surface.

What has Chinese herbs got to do with rituximab? This thread is about rituximab.

 

[Rufous McKinney]

its about that it can take a long time for the body to demonstrate the adjustments it is in fact maybe making.

sorry to bother the thread.

 

[Hip]

its about that it can take a long time for the body to demonstrate the adjustments it is in fact maybe making.

It can take a long time in some cases, but treatment can kick in within hours in other cases. It's very variable, depending on disease and treatment. In this case, we know from F&M's 2015 paper that major responses to rituximab began to manifest at the 23 week stage on average (range 8-66 weeks).

 

[Gingergrrl]

I'm going to reply to this in two parts so each post is not too long.

You missed one, @Butydoc

Butydoc was one of the people that I immediately thought of but did not mention b/c I have not spoken to him (or even seen him post) in a very long time. I was not sure if it was okay to mention him and I also do not know his current health status. But since you mentioned him @IThinkImTurningJapanese, I assume it is okay! I am actually very interested if the Rituximab helped him long-term and hoping that he will share that with us some day.

I've not looked at the Fluge and Mella studies in any detail (I find reading long articles or studies difficult).

I also find reading scientific studies very challenging. I do not have difficulty with reading in general, only with material that is heavily scientific. That is why I am truly hoping that someone more scientific can answer my questions re: the dosing differences between Phase 2 and Phase 3 b/c I truly want to understand them (including if this means that I have misinterpreted something).

Rituximab led to me being able to walk without a wheelchair, and regain normal muscle strength and breathing, after almost four years (which I never thought would happen again in my lifetime). I have encountered many people who have had drastic improvements from Ritux and I want to know what we all share in common (because these are people who have been given VERY different diagnoses by doctors). I want to do everything humanly possible to maintain this "remission" b/c I have a lot at stake and huge future decisions depend on it for me.

But I have just had a quick read, and it seems that much more rituximab was given to patients in the negative 2019 phase III study, compared to the positive 2011 phase II study.

I think that we are looking at different articles @Hip and I really want to figure this out and appreciate you (and everyone else) bearing with me! The Rituximab study that I am referring to is not from 2011 because it was not even remotely completed (let alone published) when I joined PR in mid 2014. If you are referring to a study that was completed in 2011 and calling it "Phase 2", then I am certain that we are referring to different studies.

The Rituximab Study that I had thought was "Phase 2" which was by Fluge & Mella (and several other authors) was at a later date. I am almost certain that I have a printed copy of it (somewhere?!) and will try to find it later tonight. I have family over right now but really wanted to reply to this thread! I am typing fast and will come back and edit this later for clarity and typos.

The study I am referring to involved each patient getting 1000 mg of Rituximab per dose, it involved multiple maintenance doses (I believe at 6 mos, 9 mos, 12 mos, and 15 mos) and I am almost certain that the Rituximab Protocol later given at Kolibri in Sadnes, Norway was also 1000 mg per infusion (and I knew of several responders who got treatment at Kolibri (and several non-responders as well). This is all very confusing to me and the LAST thing I want to do is mis-state something from one of the studies and hoping someone can clarify this all for me.

Or the perhaps the phase II study might have included different types of ME/CFS patient, and that's why the results were different. F&M did not test the patients for which infections they had, and given that there was an 8 year difference between the publication of these studies, perhaps there may have been an outbreak of a different virus by the time the phase III study was conducted.

This assumes that all ME/CFS is caused or maintained by a virus (vs. autoimmunity or another cause) and I am just not sure that we know yet that this is the case. Perhaps the cohort in Norway involved people with co-morbid (or misdiagnosed) autoimmune conditions?

Yes, chronic diseases are quite often misdiagnosed initially, often not because of any negligence on the part of doctors, but because diagnosis is hard.

I absolutely agree and am not saying that the doctors who diagnosed me in 2013 were negligent (although my initial PCP was because she completely missed that I had both Hashimoto's Disease and POTS). She wrote me off as having "CFS" based on absolutely nothing and then told me that there were "no treatments" and she did not need to see me again. I've shared all of this endlessly (so I don't want to waste anyone's time here!) but I agree w/you that most of the early doctors that I saw were not negligent (although some definitely were).

Another reason why chronic diseases are liable to initial misdiagnosis is because most chronic diseases start slowly, with minimal symptoms to begin with, and the symptoms gradually get worse over the years. So when a patient first goes to the doctor, the symptoms may still be quite minimal and subtle. That makes it harder to figure out what disease they might have. But say 5 years down the line, those subtle symptoms may become more severe and thus more obvious and apparent, making diagnosis easier.

I agree with this as well but have a different take on it. I think that sometimes illnesses take several years to morph into their full form and the early symptoms are too vague and ambiguous to diagnose. But I also think (and my doctors believe this is what happened in my case), that some illnesses begin with a virus such as EBV and then in later years, the EBV morphs into autoimmunity (or even cancer) in some cases. So the early doctors did not "miss" it vs. it just hadn't happened yet. In the early days, I had a post-viral fatigue syndrome from EBV but in later years, this shifted into complete autoimmune chaos (in my case).

I think that even in the early stage, had your doctors strictly followed the CCC, they probably would not have diagnosed you with ME/CFS.

I have never encountered a doctor in the US who diagnosed me using "CCC" criteria or used the term "ME". In the early days of my illness, I was given the "CFS" diagnosis because I had fatigue that followed a severe case of Mono (approx 10 months earlier), positive IgM, EA & IgG viral titers for EBV, and a myriad of other unexplained symptoms.

(you need to wait at least around 12 months or so).

My main doctor (who is an ME/CFS specialist) and is NOT one of the doctors that I referred to above, said that in most cases, you would know if you are a responder in 6-9 months. You might not have a full improvement but if you had zero improvement by month 9, than you most likely are not a responder. He had no way to predict if I would be a responder but he said that IF I was, it would most likely be earlier than the normal time-frame b/c I had already done a full year of high dose IVIG when I started Ritux (and did a 2nd year of IVIG which overlapped with the first year of Ritux). So we were hitting the autoantibodies from all angles (both the fully grown ones and killing the B-cells to stop the creation of new ones at production level).

Quite a few patients on my list had rituximab back in around 2013.

I think that we have a very different list b/c I did not even join PR until mid 2014 and everyone that is on my (informal) list had Rituximab after that point. I am also including people who are in two private FB groups that I belong to and are not members of PR (but I think that they are important b/c many of them were also initially given "CFS" diagnoses like I was). And many people in my FB groups were NOT responders to Ritux and they have identical autoantibodies as me. So there is some factor that I am trying to identify but do not yet know what it is.