Rituxan, 10 weeks in and no major changes yet

Blake2e

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I have aggressive Mast cell activation syndrome (MCAS) and I finished the Rituxan loading phase 10 weeks ago exactly. In the beginning I thought it was helping a little because it felt like my intolerance to steroids was reduced a little, but 10 weeks my intolerance to steroids is just getting worse and my other symptoms are becoming worse. My B cells are still ablated. I'm on Xolair as well. My IgE was over a 1000 at one point. at the end of the 1st month on Rituxan my IgE was about 280 and on the 2nd month it was around 380. I believe it was the Rituxan that lowered it but it seems to be increasing now. Im gonna check it again at the end of this month.

Is there a chance that the Rituxan may still work for me?
 
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If we look at Fluge and Mella's superceded Phase 2 study no patients showed a response before week 8. Most showed a response by week 20.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129898

Obviously this trial had no control arm and the much better designed Phase 3 trial found Rituximab does not work on average for the average patient. If it is going to work for you you will probably know by ~week 25. I'd say that since you've begun you may as well wait a little longer to see.
 

Gingergrrl

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I have aggressive Mast cell activation syndrome (MCAS) and I finished the Rituxan loading phase 10 weeks ago exactly. In the beginning I thought it was helping a little because it felt like my intolerance to steroids was reduced a little, but 10 weeks my intolerance to steroids is just getting worse and my other symptoms are becoming worse.
Hi Blake! I was wondering how you were doing and glad that you posted an update. Can you remind me, were you exclusively trying Ritux for your severe MCAS or was it also for other diagnoses? I can't remember, do you also have POTS or other autoimmunity?

If I remember correctly, you were hoping that the Ritux would allow you to come off of the steroids? Have you been able to reduce the steroid doses at all? I was also curious which symptoms were getting worse?

My IgE was over a 1000 at one point. at the end of the 1st month on Rituxan my IgE was about 280 and on the 2nd month it was around 380.
Did you notice if you felt better when your IgE was lower or was there no correlation between the two?

Is there a chance that the Rituxan may still work for me?
It is so hard to know and I wish I could make a prediction! I wish I knew in my case if my remission from IVIG & Ritux is permanent or temporary? I want to proceed with life as if it is permanent but am so hesitant in many ways in case it is temporary.

Can you remind me, are you also doing IVIG? I cannot remember if you were doing both or just Ritux?
 

Blake2e

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Do you have POTS?

Ever run a cell trend test?
I'm getting evaluated for it. I suspect I may have some form of POTS secondary to MCAS.

No I havent done a cell trend test but Im interested in it. I found this website https://www.celltrend.de/en/pots-cfs-me-crps.html but Im not sure if there would be a point in doing it at the moment since my B cells are shut down and I get IVIG for primary immunodeficiency. I feel like those things may interfere with results. Though since I am still symptomatic then if I have those autoantibodies then the test should be able to pick up on it.

If we look at Fluge and Mella's superceded Phase 2 study no patients showed a response before week 8. Most showed a response by week 20.

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129898

Obviously this trial had no control arm and the much better designed Phase 3 trial found Rituximab does not work on average for the average patient. If it is going to work for you you will probably know by ~week 25. I'd say that since you've begun you may as well wait a little longer to see.
Interesting so about 6 months to know for sure. Researched some more on autoimmunes and time to response seems similar. Long-lived plasma cells are probably why a long lag is seen from time of drug administration to clinical response. If it's that long of a wait then I'll need to do a combination treatment and find another drug to help with the symptoms. Maybe a proteasome inhibitor or high dose IVIG.

Edit: when you say average pt in the phase 3 trial, what do you mean by average? People in general that go on this drug or for people taking it for ME/CFS?

Hi Blake! I was wondering how you were doing and glad that you posted an update. Can you remind me, were you exclusively trying Ritux for your severe MCAS or was it also for other diagnoses? I can't remember, do you also have POTS or other autoimmunity?
I wasnt doing any updates b/c I felt stuck. Not knowing if Rituxan was working and not being able to get high dose IVIG (though I havent quit trying). Ritux for MCAS, though I may have POTS. I'm seeing a Neurologist next week to get evaluated. But as of now I am not diagnosed with any autoimmune.

If I remember correctly, you were hoping that the Ritux would allow you to come off of the steroids? Have you been able to reduce the steroid doses at all? I was also curious which symptoms were getting worse?
Before I started Rituxan, steroids had just about lost all effectiveness on me but after the infusion it felt like my tolerance to them came back. Over the past 10 weeks my steroids dosages have been climbing up high again. Angioedema, purple extremities, tachycardia, tremors, profuse putrid sweating from all over, heartburn, nausea, diarrhea (some of these symptoms are why my doc and I suspect POTS though I have no issue with standing up and laying down). I also get other more typical allergy symptoms with sinus, eyes, fatigue, migraines. Growing increasingly more sensitive to allergens,

Did you notice if you felt better when your IgE was lower or was there no correlation between the two?
I do. At 280 IgE I felt much better than I did at 380. At 280 I felt moderate fatigue, some nausea and stomach cramping and heart rate in 70s while I was waiting to get my blood drawn. At 380, I had tremors (I had trouble holding my arm still for them to draw the blood), heart rate over 120 and felt massive amounts of adrenaline coursing through veins,

It is so hard to know and I wish I could make a prediction! I wish I knew in my case if my remission from IVIG & Ritux is permanent or temporary? I want to proceed with life as if it is permanent but am so hesitant in many ways in case it is temporary.

Can you remind me, are you also doing IVIG? I cannot remember if you were doing both or just Ritux?
Im doing IVIG, 30g, for primary immunodeficiency.
 
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Edit: when you say average pt in the phase 3 trial, what do you mean by average? People in general that go on this drug or for people taking it for ME/CFS?
Their phase 3 trial was on rituximab for mecfs and it failed its primary endpoint. Which is to say they demonstrated it showed no more benefit than placebo. However the paper on the trial has not been published - we just know that it "failed".

I use the word average because the study averages out across its sample population. We cannot 100% exclude the possibility that rituximab will work for an individual - even if it is shown not to work on average.
 

Belbyr

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Their phase 3 trial was on rituximab for mecfs and it failed its primary endpoint. Which is to say they demonstrated it showed no more benefit than placebo. However the paper on the trial has not been published - we just know that it "failed".

I use the word average because the study averages out across its sample population. We cannot 100% exclude the possibility that rituximab will work for an individual - even if it is shown not to work on average.
I agree, I believe they are still sorting out all the data but there is for sure a subgroup that this benefits, otherwise there would have never been any trials. With everything they are finding in POTS/dysautonomia these days, it looks like all of that is autoimmune mediated when you factor in all the other autoimmune diseases tied to it.

When I was running the gauntlet of testing for pots, they told me they find the autoimmune cause in 40-50% of cases, now Cort is reporting with more panels they are finding 60%+ are now positive for autoimmune conditions.
 

Blake2e

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I agree, I believe they are still sorting out all the data but there is for sure a subgroup that this benefits, otherwise there would have never been any trials. With everything they are finding in POTS/dysautonomia these days, it looks like all of that is autoimmune mediated when you factor in all the other autoimmune diseases tied to it.

When I was running the gauntlet of testing for pots, they told me they find the autoimmune cause in 40-50% of cases, now Cort is reporting with more panels they are finding 60%+ are now positive for autoimmune conditions.
What's Cort?

I also had a question about ordering from Celltrend. How do you go through the process of ordering it and getting the blood drawn? Did you go to a regular lab and were they the ones who send it to Germany? The website isnt super clear about the process.
 
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Gingergrrl

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I'm getting evaluated for it. I suspect I may have some form of POTS secondary to MCAS.
Are you going to have a tilt table test (TTT)?

No I havent done a cell trend test but Im interested in it. I found this website https://www.celltrend.de/en/pots-cfs-me-crps.html but Im not sure if there would be a point in doing it at the moment since my B cells are shut down and I get IVIG for primary immunodeficiency. I feel like those things may interfere with results. Though since I am still symptomatic then if I have those autoantibodies then the test should be able to pick up on it.
Did your doctor(s) feel that the results of the Cell Trend testing could change the outcome of your treatments? If it would make absolutely no change in your IVIG or Rituximab, then it probably is not worth the financial cost and effort of shipping the blood to Germany (although it might be interesting on an academic level). I know you have been fighting to get a higher dose of IVIG and if this testing could make a difference in that, then I do think it is worth it.
In my case, I did the testing both prior to treatment, and afterwards so we could get a comparison level.

I wasnt doing any updates b/c I felt stuck. Not knowing if Rituxan was working and not being able to get high dose IVIG (though I havent quit trying). Ritux for MCAS, though I may have POTS. I'm seeing a Neurologist next week to get evaluated. But as of now I am not diagnosed with any autoimmune.
I found it helpful to write updates even when I was stuck (or getting progressively worse) prior to finding the right treatment. Best wishes for your Neuro appt. I forgot, have you done any of the Mayo Clinic panels for autoimmunity?

Before I started Rituxan, steroids had just about lost all effectiveness on me but after the infusion it felt like my tolerance to them came back. Over the past 10 weeks my steroids dosages have been climbing up high again.
I am confused, now that you are back on the steroids, are they helping your symptoms or making them worse?

Angioedema, purple extremities, tachycardia, tremors, profuse putrid sweating from all over, heartburn, nausea, diarrhea (some of these symptoms are why my doc and I suspect POTS though I have no issue with standing up and laying down).
Wow, this all sounds horrible to go through! Do you have any increase in tachycardia when you stand up, or lift your arms above your head, or bend down to pick up something from the floor, etc?

Im doing IVIG, 30g, for primary immunodeficiency.
Thanks for reminding me (and hopefully I will not ask you again)!

I agree, I believe they are still sorting out all the data but there is for sure a subgroup that this benefits, otherwise there would have never been any trials. With everything they are finding in POTS/dysautonomia these days, it looks like all of that is autoimmune mediated when you factor in all the other autoimmune diseases tied to it.
I completely agree with this and I think that time will tell if that sub-group is part of ME/CFS or a group who was misdiagnosed with ME/CFS but had a primary autoimmune diagnosis (or had both).

When I was running the gauntlet of testing for pots, they told me they find the autoimmune cause in 40-50% of cases, now Cort is reporting with more panels they are finding 60%+ are now positive for autoimmune conditions.
That is interesting and I think we may find out some day that all POTS is autoimmune.

I also had a question about ordering from Celltrend. How do you go through the process of ordering it and getting the blood drawn? Did you go to a regular lab and were they the ones who send it to Germany? The website isnt super clear about the process.
I can explain this in great detail another day when I am more alert (please remind me!) but the two best options are to go to a private specialty lab for the blood draw or to have a home phlebotomist come to your home. A regular lab like Quest or Lab Corp would not be able to do it.
 

Blake2e

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Are you going to have a tilt table test (TTT)?
Likely, but 1st appointment is just a consult (waste of time, dont know the point of a consult since my immunologist explained everything in detail) so itll likely be done in the following appointment.

Did your doctor(s) feel that the results of the Cell Trend testing could change the outcome of your treatments? If it would make absolutely no change in your IVIG or Rituximab, then it probably is not worth the financial cost and effort of shipping the blood to Germany (although it might be interesting on an academic level). I know you have been fighting to get a higher dose of IVIG and if this testing could make a difference in that, then I do think it is worth it.
In my case, I did the testing both prior to treatment, and afterwards so we could get a comparison level.
I'm going to ask Neurologist and see what he says. I dont think I have the autoimmune version as my symptoms only start up when my allergies are triggered. I dont think a diagnosis of autoimmune POTS would really help me with getting high dose IVIG. But I like taking test to have the hard facts and rule things out.

I found it helpful to write updates even when I was stuck (or getting progressively worse) prior to finding the right treatment. Best wishes for your Neuro appt. I forgot, have you done any of the Mayo Clinic panels for autoimmunity?
Thanks I think I'll write up some of my thoughts on what Im going to do next and why my treatment isnt progressing as I'd like.

I am confused, now that you are back on the steroids, are they helping your symptoms or making them worse?
I was never off the steroids but right before I started Rituxan the steroids were becoming very much useless for me (I would just react to them and they stopped helping with symptoms) but after the Rituxan infusion I was I became a bit more tolerant of them and they've been helping a little more. Problem is I'm needing higher and higher doses.

Wow, this all sounds horrible to go through! Do you have any increase in tachycardia when you stand up, or lift your arms above your head, or bend down to pick up something from the floor, etc?
None of that but maybe when I bend down to pick something up off the floor too fast, though I think thats more to do with exercise/exertion intolerance. My autonomic dysfunction symptoms pop up when my allergies are triggered. All that histamine messing with my autonomic nerves.


Thanks for reminding me (and hopefully I will not ask you again)!
Its all good.

That is interesting and I think we may find out some day that all POTS is autoimmune.
Reading this kind of thing in many places is why I want to do the blood tests for the autoantibodies despite my thinking that I dont have that autoimmune. So many similarities thats its good to try and rule it out.

I can explain this in great detail another day when I am more alert (please remind me!) but the two best options are to go to a private specialty lab for the blood draw or to have a home phlebotomist come to your home. A regular lab like Quest or Lab Corp would not be able to do it.
Thatd be awesome!
 

Gingergrrl

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Likely, but 1st appointment is just a consult (waste of time, dont know the point of a consult since my immunologist explained everything in detail) so itll likely be done in the following appointment.
Maybe the Cardio just wants to meet you and get your history and prepare you for the TTT?

I'm going to ask Neurologist and see what he says. I dont think I have the autoimmune version as my symptoms only start up when my allergies are triggered. I dont think a diagnosis of autoimmune POTS would really help me with getting high dose IVIG. But I like taking test to have the hard facts and rule things out.
For me it was further evidence of autoimmunity. At first I just had Hashimoto's and only thought of my thyroid as autoimmune but nothing else. But then slowly, I kept collecting more and more autoimmune antibodies and diagnoses so it was helpful knowing the my POTS was autoimmune b/c it meant that it could eventually respond to autoimmune treatments like Rituximab (and it did).

Thanks I think I'll write up some of my thoughts on what Im going to do next and why my treatment isnt progressing as I'd like.
:thumbsup:

I was never off the steroids but right before I started Rituxan the steroids were becoming very much useless for me (I would just react to them and they stopped helping with symptoms) but after the Rituxan infusion I was I became a bit more tolerant of them and they've been helping a little more. Problem is I'm needing higher and higher doses.
Thx for explaining. I am tapering off Cortef and it is the longest taper of my life and will be close to 1.5 years by the time it is done. But my Endo did not believe it was possible for me to come off of it and now he does. I started at 15 mg per day and am now (almost) at 8.75 mg per day with the goal to get to zero (if my blood work remains safe to do so). I prefer not to be on any steroids although when I started the Cortef I was allergic to all food and we were desperate to find something that worked.

My autonomic dysfunction symptoms pop up when my allergies are triggered. All that histamine messing with my autonomic nerves.
I know there is a HUGE correlation between POTS and MCAS, and the two almost always go hand in hand, but I still cannot remember why (even though it has been explained to me many times :bang-head:). Do you understand it? I know that histamine makes the membranes more permeable (so that third spacing of fluid often occurs) but how does this trigger POTS?

Reading this kind of thing in many places is why I want to do the blood tests for the autoantibodies despite my thinking that I dont have that autoimmune. So many similarities thats its good to try and rule it out.
If you are able to do them, I think the info could be valuable.

Thatd be awesome!
I can definitely explain it (Cell Trend) and please let me know specifically what questions you have. You can send me a PM if you prefer. My doctor's office created a kit (which was not available when I first did the testing in 2016 but is available now) so I have an instruction sheet that explains exactly what to do. Are there any private specialty labs in your area? In my state, these specialty labs can do blood draws as long as you have a signed doctor's note. The other option is using a home phlebotomy service.
 

Blake2e

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Maybe the Cardio just wants to meet you and get your history and prepare you for the TTT?
The Neuro just wanted to get to know my case directly which I understand. This neuro can treat autonomic dysfunction but doesnt have equipment need to diagnose, Only neuro in the state who has equipment to diagnose is overbooked and takes a lot of time off work.


I know there is a HUGE correlation between POTS and MCAS, and the two almost always go hand in hand, but I still cannot remember why (even though it has been explained to me many times :bang-head:). Do you understand it? I know that histamine makes the membranes more permeable (so that third spacing of fluid often occurs) but how does this trigger POTS?
“”” Patients with MCAD usually have episodes of flushing and sometimes rashes followed by autonomic symptoms. It is hypothesized that histamine release from degranulated mast cells triggers can cause excessive vasodilation and trigger a hyperadrenergic response.””” (http://www.dysautonomiainternational.org/page.php?ID=150)


] can definitely explain it (Cell Trend) and please let me know specifically what questions you have. You can send me a PM if you prefer. My doctor's office created a kit (which was not available when I first did the testing in 2016 but is available now) so I have an instruction sheet that explains exactly what to do. Are there any private specialty labs in your area? In my state, these specialty labs can do blood draws as long as you have a signed doctor's note. The other option is using a home phlebotomy service.
My neuro said I didnt need to do it yet. Can you send me that instruction sheet?
 

Gingergrrl

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The Neuro just wanted to get to know my case directly which I understand. This neuro can treat autonomic dysfunction but doesnt have equipment need to diagnose
Sorry for my confusion and I thought you were seeing a Cardio but there are also Neuros who specialize in Dysautonomia. Although both are sadly rare! Since you are seeing a Neuro, I would ask if they can order one of the Mayo Autoimmune Dysautonomia Panels for you (like PAVAL or DYS1). I can't remember if you already had one of them in the past?

This was a VERY interesting link and I have probably read it before (at some point in the last 4-5 yrs!) but it was interesting to read it again. In my case, I have no idea if (undiagnosed) MCAS triggered the POTS or vice versa. I also do not know when exactly I developed the paraneoplastic autoantibodies since I was first tested in 2016 but I already had POTS for 3 yrs by that point. I wish I had a crystal ball and could decode exactly what happened to me.

My neuro said I didnt need to do it yet. Can you send me that instruction sheet?
If you are interested in doing the Cell Trend testing on your own, you don't need a Neuro to approve it (but just need a doctor to approve the blood draw). The kit had many parts to it with one page printed from the Cell Trend website (in English) re: the different tests that they offer. Then there was another page with the blood draw instructions for the phlebotomist, and another page re: how you pay Cell Trend using PayPal and also instructions to send them an e-mail alerting them of your info, when your blood sample was sent with Fedex with the tracking #, how to use Fedex Overnight International for shipping, etc. If you want all of the info, it's probably easier to talk via PM? (I can't post the actual papers b/c they have my name and personal info all over them plus notes that I wrote).
 

Blake2e

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Sorry for my confusion and I thought you were seeing a Cardio but there are also Neuros who specialize in Dysautonomia. Although both are sadly rare! Since you are seeing a Neuro, I would ask if they can order one of the Mayo Autoimmune Dysautonomia Panels for you (like PAVAL or DYS1). I can't remember if you already had one of them in the past?
Did not know some Cardios dealt with autonomic dysfunction, thats good to know. There is 1 Neuro in my state that has the equipment to diagnose POTS, Im waiting to see her, might take a while. But I just message my main Neuro (who can treat autonomic dysfunction but lacks equipment to diagnose) about doing those blood tests you mentioned,

If you are interested in doing the Cell Trend testing on your own, you don't need a Neuro to approve it (but just need a doctor to approve the blood draw). The kit had many parts to it with one page printed from the Cell Trend website (in English) re: the different tests that they offer. Then there was another page with the blood draw instructions for the phlebotomist, and another page re: how you pay Cell Trend using PayPal and also instructions to send them an e-mail alerting them of your info, when your blood sample was sent with Fedex with the tracking #, how to use Fedex Overnight International for shipping, etc. If you want all of the info, it's probably easier to talk via PM? (I can't post the actual papers b/c they have my name and personal info all over them plus notes that I wrote).
We can talk over PM.
 

Gingergrrl

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But I just message my main Neuro (who can treat autonomic dysfunction but lacks equipment to diagnose) about doing those blood tests you mentioned
If your main Neuro will order one of the Mayo Autoimmune Dysautonomia Panels, it will be very helpful to rule in or out an autoimmune cause of your symptoms. And Mayo Panels are taken much more seriously by insurance companies (assuming you have a positive result).

We can talk over PM.
:thumbsup:
 
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I have aggressive Mast cell activation syndrome (MCAS) and I finished the Rituxan loading phase 10 weeks ago exactly. In the beginning I thought it was helping a little because it felt like my intolerance to steroids was reduced a little, but 10 weeks my intolerance to steroids is just getting worse and my other symptoms are becoming worse. My B cells are still ablated. I'm on Xolair as well. My IgE was over a 1000 at one point. at the end of the 1st month on Rituxan my IgE was about 280 and on the 2nd month it was around 380. I believe it was the Rituxan that lowered it but it seems to be increasing now. Im gonna check it again at the end of this month.

Is there a chance that the Rituxan may still work for me?
At Center for Complex Diseases, their experience is that it takes 4-6 months (usually) to see major improvement, if you're going to respond. They say that they've had non-responders, but have not had a patient permanently worsen from Rituxan. I have neuroimmune disease, Lyme/other TBD, neurological autoimmune disease, EDS, PID, NKCF deficiency, and moderate to severe MCAS.
 

Blake2e

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At Center for Complex Diseases, their experience is that it takes 4-6 months (usually) to see major improvement, if you're going to respond. They say that they've had non-responders, but have not had a patient permanently worsen from Rituxan. I have neuroimmune disease, Lyme/other TBD, neurological autoimmune disease, EDS, PID, NKCF deficiency, and moderate to severe MCAS.
What Rituxan is doing for me seems very strange. In the 1st month after infusion I start to feel better, maybe a 30% cut in sensitivity to allergies. Then after that month it slowly stops working until the end of the 2nd month I quickly get worse. As of now Im scheduled to get infusions every 2 months for I believe the next 6 months.