Doctor proposing Rituximab trial for autoimmunity

JasonUT

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Hello,

My doctor is proposing Rituximab treatment for autoimmunity. However, I don't feel my lab data is very compelling for autoimmunity.

ANA titer:
Positive 2 of 8 times with positive value of 1:40 (Ref Range < 1:40)

Mayo Dysautonomia Autoimmune Panel (3 times)
a. N-Type Calcium Channel Ab (VGCC): 0.10
(7/11/2018), 0.51 (3/30/2019), 0.22 (5/3/2020) (Ref Range < 0.03)
b. Neuronal K+ Channel Ab (VGKC) 0.07
(7/11/2018), 0.03 (3/30/2019), 0.03 (5/3/2020) (Ref Range < 0.02)

All other autoimmunity panels negative.

What do you think?

Background info:
I have been suffering with health issues since 2014. Diagnosis currently include POTS confirmed twice via TTT, vestibular migraines, central vestibular issues confirmed via VNG, intractable headaches, and ME/CFS.

I'm seeing some improvement with Clonidine transdermal patch for POTS and Cyproheptadine for headaches and Vestibular therapy for central vestibular issues.

Prior to the three above treatments, I was bed bound 23 hours per day, and now I'm bed bound/couch bound approximately 16-18 hours per day and house bound the remainder of the day.

My common component seems to be the brain stem which includes the vestibular nuclei (my vestibular issues) and autonomic nervous system (POTS).
 

lenora

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Hello @JasonUT......If the brainstem is the main source of your problems, has a series of MRI's been done to confirm this?

Have as many different doctors as possible read them (not just the report). Things are sometimes found by one doctor while another may miss it entirely. Also, with the brainstem you may have many other different symptoms....heart, breathing problems, that type of thing. Do you?

Migraines are hard to treat, have you been given samples of different drugs to try? I'm sorry that you're as ill as you are....I hope things improve soon. It's surprising how many of us suffer from migraines in addition to so many other symptoms. At least I was lucky enough to postpone them until just recently.

Which part of the country are you in? Have you tried to find a clinic specializing in this illness? Yours, Lenora.
 

Pyrrhus

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You might consider asking your doctor to consider immunoglobulin therapy (IVIG or SCIG) instead of Rituximab.

Although some people with ME report that they have benefitted from Rituximab, others have reported that their lives were destroyed by the Rituximab treatment.

ANA titer:
Positive 2 of 8 times with positive value of 1:40 (Ref Range < 1:40)

Mayo Dysautonomia Autoimmune Panel (3 times)
a. N-Type Calcium Channel Ab (VGCC): 0.10
(7/11/2018), 0.51 (3/30/2019), 0.22 (5/3/2020) (Ref Range < 0.03)
b. Neuronal K+ Channel Ab (VGKC) 0.07
(7/11/2018), 0.03 (3/30/2019), 0.03 (5/3/2020) (Ref Range < 0.02)

All other autoimmunity panels negative.
Personally, I feel you're right to question your doctor's assumption of autoimmunity.
 

Gingergrrl

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My doctor is proposing Rituximab treatment for autoimmunity. However, I don't feel my lab data is very compelling for autoimmunity.
Hi Jason, we talked a few years ago on PR re: the N-type Calcium Channel Autoantibody and other autoimmune issues & treatments (but I'm not sure if you remember)? I don't post a lot on PR these days but still participate in several ongoing PM's and try to reply to posts like this if I think I might be able to help.

ANA titer:
Positive 2 of 8 times with positive value of 1:40 (Ref Range < 1:40)
I agree that your ANA result alone is not meaningful and most labs consider an ANA titer of 1:40 to be negative and only consider 1:80 or higher to be positive. My ANA titer is usually 1:160, speckled pattern (in case this is of any use)?

Mayo Dysautonomia Autoimmune Panel (3 times)
a. N-Type Calcium Channel Ab (VGCC): 0.10
(7/11/2018), 0.51 (3/30/2019), 0.22 (5/3/2020) (Ref Range < 0.03)
b. Neuronal K+ Channel Ab (VGKC) 0.07
(7/11/2018), 0.03 (3/30/2019), 0.03 (5/3/2020) (Ref Range < 0.02)
You consistently test positive for both calcium channel and potassium channel autoantibodies on the Mayo Panels and am confused why you dismiss this as insignificant? The Mayo Panels are highly accurate and are showing that you have two ion channelopathies. Can you remind me who your doctor is? For some reason, I remember that you were seeing Dr. Vernino (but I may be completely remembering this wrong)!

All other autoimmunity panels negative. What do you think?
I would take the results of the Mayo Panels very seriously (if I was in your shoes). I have tested positive for the N-type CA+ Channel Ab like you since 2016 (but I am negative for the Potassium Channel Abs). I also have some other positive autoantibodies in addition.

There is an excellent private group on FB re: the N-type CA+ Channel Ab and I can give you the info in case you are interested. It is a great group of people and they have really helped me in the past (and I tend to ask a lot of questions ;)).

The treatments that put me into remission were high-dose IVIG followed by Rituximab. I did infusions for 3 years total. The first year just IVIG, the second year I overlapped the IVIG & Rituximab, and the third year, just Rituximab. I also benefit from other medications (for MCAS, POTS, endocrine issues, etc) but those meds alone were for symptom relief and did not get to the root of the problem like the IVIG & Ritux did.

I have been suffering with health issues since 2014. Diagnosis currently include POTS confirmed twice via TTT, vestibular migraines, central vestibular issues confirmed via VNG, intractable headaches, and ME/CFS.
We are very similar re: POTS (mine had also been confirmed twice by TTT) but I never had migraines/ headaches, or vestibular issues. What I had that you didn't mention was progressive muscle weakness that affected my breathing, severe MCAS & allergic reactions, and thyroid/adrenal issues.

Can you remind me if you have done the cancer screenings since you test positive for two paraneoplastic autoantibodies?
 

Hoosierfans

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Hey @Pyrrhus, you mentioned that some folks report that their lives were destroyed by Rituximab. That’s terrifying! Can you elaborate? Was this a large number of patients? Whitney Dafoe is the only person I am aware of that had the Rituximab have such a drastic negative effect. It may be in the cards for me in the future so I am curious. Thanks!
 

jaybee00

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I don’t think that’s true about rituximab (lives destroyed)—haven’t heard that. The RCT study of rituximab demonstrated that it had no effect on MECFS—but if you look at the patent application by Fluge there was *one* patient who apparently did respond. https://forums.phoenixrising.me/thr...-against-plasma-cells-2021-fluge-mella.83692/

As far as immunosuppressive drugs, there is evidence for cyclophosphamide helping MECFS (especially for the patients with the two risk alleles) but it was an open label trial https://www.s4me.info/threads/intra...-study-2020-rekeland-mella-fluge-et-al.14925/
 

Hoosierfans

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Why would you take an expensive drug with no demonstrated effect on MECFS?
For several reasons. First, while I carry an ME / CFS diagnosis on my chart, I don’t experience PEM. So to the extent studies don’t show effect on PEM, it doesn’t quite apply to me. Second, my illness (still working on exactly what the drivers are) appears to be autoimmune driven. I recently tested positive for many Celltrend antibodies. Third, I have SFN. So at this point my internist is working on getting me into see a neuroimmunologist but we’ve discussed what we *think* they will recommend and he thinks I’m headed for IVIG and / or Rituximab.
 

Gingergrrl

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For several reasons.
Aren't you also positive for anti-Hu autoantibodies (from another public thread where you were talking about this w/me & @crypt0cu1t)? I hope I am not remembering this wrong!

In cases like mine where someone has multiple autoantibodies that are behaving in a pathogenic way with progressively worsening symptoms, my doctor felt that high-dose IVIG was literally the only logical next step (and I agreed 100%). When I was a clear responder to IVIG, then he was able to make a solid case for Rituximab vs. IVIG in which the benefits are often like a band-aid and often stop once you stop the IVIG.
 

Learner1

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In cases like mine where someone has multiple autoantibodies that are behaving in a pathogenic way with progressively worsening symptoms, my doctor felt that high-dose IVIG was literally the only logical next step (and I agreed 100%). When I was a clear responder to IVIG, then he was able to make a solid case for Rituximab
I had a similar situation, and did IVIG and then Rituximab. As I was immunodeficient to begin with, I've continued IVIG after the Rituximab.

It has been successful, and I'm thankful I had the opportunity.
You might consider asking your doctor to consider immunoglobulin therapy (IVIG or SCIG) instead of Rituximab.
Typically, patients have infections treated first, then do IVIG, and if that's all successful, then they move in to Rituximab.
Although some people with ME report that they have benefitted from Rituximab, others have reported that their lives were destroyed by the Rituximab treatment.
Before I did Rituximab, I got a second opinion from a doctor who specializes in both autoimmunity and immunodeficiency. We discussed stem cells and bortezimub as well, and he thought that Rituximab was the least risky solution and just might work. He suggested I ensure that I didn't have any live infections, as that wouldn't be good if we removed my antibodies, and then I get any antibodies tested that I wanted to know about before starting the IVIG, because once you start the IVIG you're getting other people's antibodies showing up on tests.

@Pyrrhus I know of two possible cases where Rituximab made patients worse. In both cases, it is not clear that these patients had their infections treated first. Then their antibodies were wiped out by the rituximab. Not a good scenario.

However, like I said the second opinion I got thought it would not be risky. I did get one virus I wasted my treatment, which lingered for a while, but as I kept on doing the IVIG throughout the rituximab treatment and after, that gave me antibodies to be able to fight the virus and it went away. I think in these other cases where they were negative outcomes, those patients were not on IVIG throughout.
The RCT study of rituximab demonstrated that it had no effect on MECFS—but if you look at the patent application by Fluge there was *one* patient who apparently did respond. https://forums.phoenixrising.me
There are several patients who have responded, both in that trial, as well as over the past 6 years. Each of these patients was carefully selected to have autoimmunity as gingergrrl explained.
As far as immunosuppressive drugs, there is evidence for cyclophosphamide helping MECFS (especially for the patients with the two risk alleles) but it was an open label trial https://www.s4me.info/threads/intra...-study-2020-rekeland-mella-fluge-et-al.14925/
Cyclophosphamide is a very dangerous drug that is given to cancer patients. It is known to damage mitochondria, as well as cause cancer. There are many other less risky things to try.

Looking at clinical trials where patients were only selected by having ME/CFS, but they were not segmented by which infections they had or didn't have, and what immune system characteristics they had or didn't have, along with any autoimmunity, it sort of a garbage and garbage out proposition. Only when patients are carefully selected to be similar to one another, beyond just having vanilla ME/CFS, are we going to get decent results. The current theory is that we are a mixed basket of etiologies, disease drivers, metabolomics, autoimmunity, infections, toxicity, and genetic factors, with different subsets of symptoms and comorbidities, so expecting this variable group to have the same outcome from any treatment is extremely unrealistic.
Why would you take an expensive drug with no demonstrated effect on MECFS?
What do you think?
I think you should discuss it further with your doctor, and insist upon ensuring you have all of your infections tested for and treated and do IVIG for about 12 to 18 months prior to starting Rituximab. These factors seem to have led to success. One other thing that some patients have tried is plasmapharesis, which is a physical remover of antibodies. It's temporary until the antibodies grow back, but if symptoms improve once the antibodies are removed, it would likely predict the probability of success for rituximab as a more permanent treatment.
 

Gingergrrl

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There are several patients who have responded, both in that trial, as well as over the past 6 years. Each of these patients was carefully selected to have autoimmunity as gingergrrl explained.
Even though it's never possible to predict in advance who will be a responder to any med or treatment, I totally agree w/you re: the key with Rituximab is selecting patients who have a known, proven history of autoimmunity vs. randomly.

Cyclophosphamide is a very dangerous drug that is given to cancer patients. It is known to damage mitochondria, as well as cause cancer. There are many other less risky things to try.
I wholeheartedly agree with this and Cyclophosphamide is a very dangerous drug that is known to cause cancer.

I think you should discuss it further with your doctor, and insist upon ensuring you have all of your infections tested for and treated and do IVIG for about 12 to 18 months prior to starting Rituximab. These factors seem to have led to success.
I also agree that it is critical to make sure that someone does not have active infections prior to starting Rituximab. I was tested for TB, hepatitis, and other viruses, and we made sure that I did not have any active infections prior to starting Ritux. I also did IVIG for 12 months prior to starting Ritux.

One other thing that some patients have tried is plasmapharesis, which is a physical remover of antibodies. It's temporary until the antibodies grow back, but if symptoms improve once the antibodies are removed, it would likely predict the probability of success for rituximab as a more permanent treatment.
I never did plasmapheresis b/c both of my doctors (at that time) felt that it would not be safe for me. It is a much quicker way to test if someone gets symptom relief with the physical removal of antibodies. I actually would have tried it but my doctors were not comfortable with it for me and would not approve it so I will never know if I would have been a responder.
 
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Hoosierfans

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@Learner1 and @Gingergrrl, one of the things you both said kind of begs the question. You both mentioned that your docs tested to make sure you didn’t “have any active infections” prior to starting Rituximab. There’s a lot of debate in this and amongst the general chronic illness / CIRS / lyme community about what constitutes an “active infection” when one has negative PCRs, negative IGM but high IGG titers.

Can you expand upon what your docs prescribing IVIG / Rituximab considered “active.” In other words, if they saw a negative PCR, negative IGM, but IGGs remained high, would they let you go forward w/ Rituximab or would they require you to get your IGG levels down?
 

lenora

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@Hoosierfans....@Pyrrhus is probably in the midst of daytime actitvities at this point (given the time difference). Why don't you see what his response is concerning the rituximab ? I'm afraid that I don't have any info for you, but am interested and will continue to follow this matter. You'll receive an answer, I'm sure. It's an interesting subject and I would also like more information. Feel better. Yours, Lenora.
 

Hoosierfans

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@Gingergrrl yes with respect to the Anti-Hu. I tested positive in December, but my neurologist wanted to repeat the test. I’m waiting on those results now.

As my illness seems to have a strong autoimmune component (anti-Hu, CellTrend antibodies, and now I just got back Cunningham results which show anti-dopamine antibodies and anti-tibulin antibodies), I feel comfortable that IVIG is the right way to proceed for me. And, maybe eventually Rituximab depending on what my doctors decide.
 

Gingergrrl

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@Learner1 and @Gingergrrl, one of the things you both said kind of begs the question. You both mentioned that your docs tested to make sure you didn’t “have any active infections” prior to starting Rituximab. There’s a lot of debate in this and amongst the general chronic illness / CIRS / lyme community about what constitutes an “active infection” when one has negative PCRs, negative IGM but high IGG titers.
I know that there are many schools of thought re: what constitutes an active Lyme infection and unfortunately I don't have any experience with this and hoping that someone else can give you feedback who knows more about it. I consistently tested negative on Lyme & tick-borne infections on all tests so it wasn't an issue in my case.

The specific issues that my doctor tested me for prior to Rituximab were to confirm that I had never had TB or hepatitis (at any point in my life) b/c they can both reactivate and become very dangerous (from Rituximab). Luckily, I'd never had either, which the testing confirmed, so this was not an issue for me.

Lastly, my doctor also ordered a special test to make sure that I was not IgM positive for the JC virus (which could make someone at higher risk of PML from Rituximab) and I was negative. I did have IgG antibodies which meant I probably had a mild infection as a child but my doctor was not concerned about that.

Can you expand upon what your docs prescribing IVIG / Rituximab considered “active.” In other words, if they saw a negative PCR, negative IGM, but IGGs remained high, would they let you go forward w/ Rituximab or would they require you to get your IGG levels down?
As far as I recall, my doctor was not concerned about IgG antibodies as long as the PCR tests were negative. There was a point in my life that I was PCR positive for EBV but that was several years apart from the Rituximab.

WRT to infections, patients with latent TB might be advised against getting rituximab due to potential of reactivating TB.
Also testing for hepatitis in addition to testing for TB.
 

Pyrrhus

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@Pyrrhus I know of two possible cases where Rituximab made patients worse. In both cases, it is not clear that these patients had their infections treated first. Then their antibodies were wiped out by the rituximab. Not a good scenario.
Excellent point.
Unfortunately, there are just so many infections that we still do not know how to test for, much less treat.

Cyclophosphamide is a very dangerous drug that is given to cancer patients. It is known to damage mitochondria, as well as cause cancer. There are many other less risky things to try.
Another excellent point.

One other thing that some patients have tried is plasmapharesis, which is a physical remover of antibodies. It's temporary until the antibodies grow back, but if symptoms improve once the antibodies are removed, it would likely predict the probability of success for rituximab as a more permanent treatment.
That sounds like a good suggestion.
Plasmapheresis might give a "preview" of what Rituximab would be like.

@Pyrrhus is probably in the midst of daytime actitvities at this point (given the time difference). Why don't you see what his response is concerning the rituximab ?
Aww, thank you so much for the vote of confidence, @lenora !
In this case, I think @Learner1 and @Gingergrrl might be more informed than I am.
 

Learner1

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IVIG is given to rituximab patients if they develop low IG (hypogammaglobulinemia) after treatment.

https://academic.oup.com/qjmed/article/107/10/821/2890483
As far as I know, my doctor has only been prescribing Rituximab after patients have already been on IVIG for about 12 months, and he typically continues it throughout the rituximab treatment. For some patients, they discontinue the IVIG when the coast seems to be clear, but for others who may have been immunodeficient to start with or have ongoing immunodeficiency, they stay on IVIG.
Can you expand upon what your docs prescribing IVIG / Rituximab considered “active.” In other words, if they saw a negative PCR, negative IGM, but IGGs remained high, would they let you go forward w/ Rituximab or would they require you to get your IGG levels down?
As far as I recall, my doctor was not concerned about IgG antibodies as long as the PCR tests were negative.
As @Pyrrhus points out We don't even know how to test for some infections, and for others there are not good PCR tests. Obviously, if one is in discussion to be getting a drug like Rituximab or even IVIG, one is talking to a doctor that has expertise and opinions on testing for infections. My doctor had been an AIDS doctor for many years with the experience of seeing all kinds of infections play out, and he treats patients individually, looking at their health history and then making educated guesses as to what to look for. But each patient is different and each doctor is different.
 

Hoosierfans

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Thank you @Learner1 and @Gingergrrl for clarifying. And @Pyrrhus for weighing in. I had an appointment with my internist yesterday and consistent with what you said, he was most concerned with Hepatitis and TB. And we discussed that we probably wouldn’t even touch Rituximab until 12-18 months of IVIG or plasmapheresis.

Oh, and my repeat Anti-Hu came back negative, thank goodness. So we will be pursuing IVIG based on the high levels from CellTrend and also 3 positive antibodies on the Cunningham. 👍🏻
 

Gingergrrl

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As @Pyrrhus points out We don't even know how to test for some infections, and for others there are not good PCR tests. Obviously, if one is in discussion to be getting a drug like Rituximab or even IVIG, one is talking to a doctor that has expertise and opinions on testing for infections. My doctor had been an AIDS doctor for many years with the experience of seeing all kinds of infections play out, and he treats patients individually, looking at their health history and then making educated guesses as to what to look for. But each patient is different and each doctor is different.
I agree with all of this (and you have a smart doctor ;))

Thank you @Learner1 and @Gingergrrl for clarifying. And @Pyrrhus for weighing in. I had an appointment with my internist yesterday and consistent with what you said, he was most concerned with Hepatitis and TB. And we discussed that we probably wouldn’t even touch Rituximab until 12-18 months of IVIG or plasmapheresis.
I agree with this, too. Although, my understanding of plasmapheresis is that you will know fairly quickly if you are a responder or not (vs. IVIG which can take much longer to know).

Oh, and my repeat Anti-Hu came back negative, thank goodness.
That is really great news! :thumbsup: