Rituximab for severe ME. Should i try?

[Gingergrrl]

I find it odd that many here have certain beliefs about this drug. It is not chemotherapy, it is a monoclonal antibody.

Am asking this out of sincerity as I want to learn and understand more about this (vs. having odd beliefs about RTX or any immunosuppressants!) My neuro said that RTX is a chemotherapy and that in someone with an increased cancer risk like me (b/c of certain auto-antibodies that I test positive for), that taking RTX or any immunosuppressant does increase my cancer risk in future years.

It does not mean that the trade-off could not be worth it and nothing is off the table at this point. And the biggest risk for me with any of these treatments is anaphylaxis b/c I have MCAS and not even sure I could handle the pre-meds. But my question is... why do some docs consider this a chemo med with increased cancer risk and some do not? I have no articles to site and am just asking the question so I can learn more.

 

[Marky90]

Am asking this out of sincerity as I want to learn and understand more about this (vs. having odd beliefs about RTX or any immunosuppressants!) My neuro said that RTX is a chemotherapy and that in someone with an increased cancer risk like me (b/c of certain auto-antibodies that I test positive for), that taking RTX or any immunosuppressant does increase my cancer risk in future years.

It does not mean that the trade-off could not be worth it and nothing is off the table at this point. And the biggest risk for me with any of these treatments is anaphylaxis b/c I have MCAS and not even sure I could handle the pre-meds. But my question is... why do some docs consider this a chemo med with increased cancer risk and some do not? I have no articles to site and am just asking the question so I can learn more.

Wiki nails it pretty well:

"Traditional chemotherapeutic agents are cytotoxic, that is to say they act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract, and hair follicles. This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence also immunosuppression), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss).

Some newer anticancer drugs (for example, various monoclonal antibodies) are not indiscriminately cytotoxic, but rather target proteins that are abnormally expressed in cancer cells and that are essential for their growth. Such treatments are often referred to as targeted therapy (as distinct from classic chemotherapy) and are often used alongside traditional chemotherapeutic agents in antineoplastic treatment regimens."

With regards to proposed cancer risk: http://www.rheumatology.org.uk/about_bsr/press_releases/biologics_cancer.aspx

 

[Jonathan Edwards]

Am asking this out of sincerity as I want to learn and understand more about this (vs. having odd beliefs about RTX or any immunosuppressants!) My neuro said that RTX is a chemotherapy and that in someone with an increased cancer risk like me (b/c of certain auto-antibodies that I test positive for), that taking RTX or any immunosuppressant does increase my cancer risk in future years.

It does not mean that the trade-off could not be worth it and nothing is off the table at this point. And the biggest risk for me with any of these treatments is anaphylaxis b/c I have MCAS and not even sure I could handle the pre-meds. But my question is... why do some docs consider this a chemo med with increased cancer risk and some do not? I have no articles to site and am just asking the question so I can learn more.

Dear Gingergrll,
When I introduced the use of rituximab for non-haematologic autoimmune disease I very deliberately did not avoid patients with cancer or cancer history. In my view it was important to establish whether or not there was any risk and since there was no theoretical basis for risk I thought we should allow people with cancer history to have treatment. They were denied anti-TNF treatment because when anti-TNF was introduced it was decided to assume that cancer might be a problem. Twenty years later we know it is not in fact a problem, with some minor possible reservations.

So there has been no reason to think rituximab would increase the risk of cancer and as far as I know there is no evidence for such a risk. In my view your neurologist is being misleading about calling this chemotherapy because chemotherapy just means drug therapy, or in lay man's terms means the sort of old fashioned cancer therapy that makes people sick. There is no reason to use the term for rituximab. And it seems the doctor is ignorant if they suggest it will increase the risk of cancer, for the reasons I have given.

I am afraid that doctors are very ready to give opinions without actually knowing about a subject in detail. I have done it many times myself in the past - we get trained to do it because it is supposed to 'reassure patients'. That is the reason why some doctors say one thing and some say another. All I can say is that I started this treatment and so far have had no information that it might lead to an increase in risk of cancer. I may have missed something but the web sites that talk about all sorts of side effects are simply reporting what happens by chance. We have no reason to think all of that is actually due to the drug. The infection risks are real, if uncommon. The hypersensitivity reactions are very rare if infusions are properly monitored.

 

[Gingergrrl]

@Jonathan Edwards Thank you for explaining more on RTX and it's relationship to chemotherapy and cancer risk and that was very helpful. After hearing this, I think the bigger risks with it for me are probably infection and anaphylaxis. It is not actually being proposed for me at this time but am keeping it in mind for the future.

Is there ever a sure-fire way to know if a specific auto-antibody is in the B-cells vs. another part of the blood? Sorry if this is a dumb question or if I already asked you this and am not remembering!

 

[Jonathan Edwards]

@Jonathan Edwards Thank you for explaining more on RTX and it's relationship to chemotherapy and cancer risk and that was very helpful. After hearing this, I think the bigger risks with it for me are probably infection and anaphylaxis. It is not actually being proposed for me at this time but am keeping it in mind for the future.

Is there ever a sure-fire way to know if a specific auto-antibody is in the B-cells vs. another part of the blood? Sorry if this is a dumb question or if I already asked you this and am not remembering!

All antibodies come from B cells - that is the specific job of B cells and no other cells. The actual production occurs when the B cells have matured and come to live in bone marrow - and the antibody is released to dissolve in the plasma. So plasmapheresis gets rid of the made antibody but B cell depletion gets rid of cells that can make antibody.

 

[Marky90]

All antibodies come from B cells - that is the specific job of B cells and no other cells. The actual production occurs when the B cells have matured and come to live in bone marrow - and the antibody is released to dissolve in the plasma. So plasmapheresis gets rid of the made antibody but B cell depletion gets rid of cells that can make antibody.

And rtx reaches the b-cells in the marrow? I thought i read somewhere that it might not, but I might have confused the spleen or lymph nodes with the marrow..

 

[Jonathan Edwards]

And rtx reaches the b-cells in the marrow? I thought i read somewhere that it might not, but I might have confused the spleen or lymph nodes with the marrow..

Rituximab does not dal with B cells that have turned into mature plasma cells and settled in marrow, no. So you have to wait for those to all die off. Autoantibody secreting plasma cells may be shorter lived and only reach the spleen but this gets a bit complicated and we do not know the detail.

 

[dannybex]

I must add that many of the patients that responded in the poll are very sick, and it looks like the majority of them are travelling far to receive the treatment which is in a clinic in Western Norway. For a moderate ME sufferer just the travel itself could lead to deterioration that could last for weeks.

Agreed.

@NL93, I am in no position to reccommend you to do anything. We don't know enough about RTX for ME yet, but I think you should make a decision based on published studies, and on the experience from Haukeland University Hospital (and perhaps Kogelnik). Patients who say that their ME occured after classic EBV onset, viral infections, throat infection, pneunomia, GI infection, and borrelia were included in the study published in 2015 (Fluge et al). No serious side effects have been registered.

And as others have mentioned on other threads, no significant benefits either. From the 2015 paper, Fluge and Melia made this clear:

" Although the treatment had a slight beneficial effect on two out of four patients with very severe ME/CFS, none of the four will be characterized as responders. B-cell depletion using rituximab for ME/CFS is at present an experimental treatment, and more evidence is needed. We do not encourage the use of rituximab for ME/CFS outside of approved clinical trials, and this is especially important for the group with very severe disease."

 

[BurnA]

Agreed.



And as others have mentioned on other threads, no significant benefits either. From the 2015 paper, Fluge and Melia made this clear:

" Although the treatment had a slight beneficial effect on two out of four patients with very severe ME/CFS, none of the four will be characterized as responders. B-cell depletion using rituximab for ME/CFS is at present an experimental treatment, and more evidence is needed. We do not encourage the use of rituximab for ME/CFS outside of approved clinical trials, and this is especially important for the group with very severe disease."

This related to very severe.
It might come down to definitions of severe versus very severe.

 

[Marky90]

Rituximab does not dal with B cells that have turned into mature plasma cells and settled in marrow, no. So you have to wait for those to all die off. Autoantibody secreting plasma cells may be shorter lived and only reach the spleen but this gets a bit complicated and we do not know the detail.

Yeah right, Iv`e read you point that out before.. But ordinary b-cells in the marrow get washed out, or? Just trying to improve my understanding a bit..

Edit: Iv`e been a bit unsure if rtx is as effective against b-cells in organs, as in plasma..

 

[deleder2k]

@dannybex, you are right about that. They are referring to those classified as very severe. I think they are considered bedridden most - or all of the time. I don't know if the author of this thread is classified as "very severe" or not, but it is indeed a valid point.

I'd just like to add in that dr. Maria Gjerpe (who received Rituximab and considered herself healthy this day) had to use a wheelchair to be able to get her first infusions. She was unsure if it is worth getting the first infusion or not. She was so sick that I am pretty sure she was classified as "very severe". But who knows.

We know that the response rates is not as good in very severe cases, but there have been a few who I would classify as severe cases who have responded very well.

In the study published in 2015 (Fluge et al.) patients with a very low function level responded favourably. One patient from 10 to 100, one from 5 to 100. One from 20 to 85. 15 to 90. 25 to 85. 10 to 85. 5 to 60. and 5 to 60 again. At 60% you can probably have a part time job. Going from being bedridden to being able to work part time must be like being reborn.

At 5% level of functioning I think one is bedridden almost every hour, every day. Needs help to go to the toilet. At 15% one is not bedridden for most of the time, but housebound. Walking is almost impossible, and wheelchair maybe needed if one is going outside the house.

The study I refer to wasn't double-blinded, but it looks like the response rate was similar to the blinded study in 2011.

 

[Gingergrrl]

All antibodies come from B cells - that is the specific job of B cells and no other cells. The actual production occurs when the B cells have matured and come to live in bone marrow - and the antibody is released to dissolve in the plasma. So plasmapheresis gets rid of the made antibody but B cell depletion gets rid of cells that can make antibody.

@Jonathan Edwards So if someone was already testing positive for auto-antibodies, then would they hypothetically require plasmapheresis to get rid of the mature ones and then something like Ritux to get rid of the new ones? Would this be the most logical approach?

 

[Gingergrrl]

Yeah right, Iv`e read you point that out before.. But ordinary b-cells in the marrow get washed out, or? Just trying to improve my understanding a bit..

Edit: Iv`e been a bit unsure if rtx is as effective against b-cells in organs, as in plasma..

I am trying to understand this as well. If RTX washes out the b-cells in the plasma or bone marrow, too?

 

[NL93]

@dannybex, you are right about that. They are referring to those classified as very severe. I think they are considered bedridden most - or all of the time. I don't know if the author of this thread is classified as "very severe" or not, but it is indeed a valid point.

I'd just like to add in that dr. Maria Gjerpe (who received Rituximab and considered herself healthy this day) had to use a wheelchair to be able to get her first infusions. She was unsure if it is worth getting the first infusion or not. She was so sick that I am pretty sure she was classified as "very severe". But who knows.

We know that the response rates is not as good in very severe cases, but there have been a few who I would classify as severe cases who have responded very well.

In the study published in 2015 (Fluge et al.) patients with a very low function level responded favourably. One patient from 10 to 100, one from 5 to 100. One from 20 to 85. 15 to 90. 25 to 85. 10 to 85. 5 to 60. and 5 to 60 again. At 60% you can probably have a part time job. Going from being bedridden to being able to work part time must be like being reborn.

At 5% level of functioning I think one is bedridden almost every hour, every day. Needs help to go to the toilet. At 15% one is not bedridden for most of the time, but housebound. Walking is almost impossible, and wheelchair maybe needed if one is going outside the house.

The study I refer to wasn't double-blinded, but it looks like the response rate was similar to the blinded study in 2011.

I just read this in the Fluge &Mella cyclophosphamide study:

Exclusion Criteria:

• Patients with fatigue who do not comply by the diagnostic "Canadian" criteria (2003) for ME/CFS
• Duration of ME/CFS less than 2 years
• Mild ME/CFS
• Very severe ME/CFS (bedridden requiring help for all tasks)

So, i am probably not "very severe" by their standards, just "severe" (Btw, who came up with this mild-moderate-severe scale? A better scale would be: severe -very severe- very extremely severe- very extremely profoundly severe, because an illness is not "mild" when a previously healthy person is now only capable of working 10 hours a week, but that is a different discussion. )
Anyways,
I still feel that for me rituximab is more risky than for a moderate sufferer, since a small relapse could make me "very severe", and it might be very hard to recover from there.

I'm probably functioning at 5% now. Would be very very happy with 60%. Or 100%. Those examples do give a lot of hope.

 

[Jonathan Edwards]

Yeah right, Iv`e read you point that out before.. But ordinary b-cells in the marrow get washed out, or? Just trying to improve my understanding a bit..

Edit: Iv`e been a bit unsure if rtx is as effective against b-cells in organs, as in plasma..

Bone marrow is where B cells are born and where they return to make antibody (as plasma cells). Precursor B cells may not be touched by rituximab but after a day or so of development, as soon as they are true B cells, they are killed. So rituximab clears fully formed B cells from marrow. It also prevents any new B cells forming for 6 months - for reasons that we do not fully understand. Rituximab will kill B cells in tissues but maybe not where they are protected by molecules like CD55 (complement decay-accelerating factor) in follicles in nodes and spleen.

 

[Jonathan Edwards]

@Jonathan Edwards So if someone was already testing positive for auto-antibodies, then would they hypothetically require plasmapheresis to get rid of the mature ones and then something like Ritux to get rid of the new ones? Would this be the most logical approach?

In most autoimmune conditions rituximab is all that is needed. Plasmapheresis is used in neurological conditions where antibodies can cause irreversible brain damage and rapid clearance is a priority. Some autoantibodies are produced by long lived plasma cells (like anti-Ro in lupus) and neither approach has much impact on long term levels, so there we have no real answers.

 

[EtherSpin]

No, I seriously doubt it. In fact I am unable to completely extend my elbows, due to a bicycle mishap about 40 years ago. Fortunately I landed on my palms, with elbows taking the shock of landing, instead of my face!

the fact that you can talk about being on a bike 40 years ago suggests that there was plenty of time in your lifespan for hypermobility to turn to stiffness - I am type 3 in a broad family history of EDS and my hypermobility disappeared with onset of CFS - perhaps from the inaction or perhaps cause I was coming into my 30's.
one of my kids however is very hypermobile and when I did dance classes as a kid ( my parents unwittingly trying to treat EDS coordination issues pre diagnosis) I could do the most difficult twisted positions from the first couple of lessons

 

[Gingergrrl]

In most autoimmune conditions rituximab is all that is needed. Plasmapheresis is used in neurological conditions where antibodies can cause irreversible brain damage and rapid clearance is a priority. Some autoantibodies are produced by long lived plasma cells (like anti-Ro in lupus) and neither approach has much impact on long term levels, so there we have no real answers.

Thank you for all the detailed explanations you have given in this thread. I am getting the sense that plasmapheresis is really no longer used in the US outside of cancer treatment. Is this accurate? Would the combination of IVIG and RTX ever be appropriate for reducing and eliminating auto-antibodies? If so, which one would commonly be done first?

 

[morse27]

 

[Apple]

Might it be worth trying to get some decent treatment for your POTS? Before trying something which is arguably quite extreme in your fragile state. I don't speak from experience due to unhelpful drs, but i've heard of some people having huge improvements in functioning after getting the right mix of meds for POTS/OI.