Using a Sledgehammer to Crack a Nut

[Justin30]

Am curious re: the two above posts (@Justin30 and @daisybell) why RTX is more of a sledgehammer vs. IVIG? I do not know the answer and am asking in complete seriousness b/c I may end up in the position of choosing.

It will ultimately depend on what my doctors recommend and what my insurance will authorize. I have another appt and test before anything is decided (so earliest would be in May where we really discuss the options.)

For me, in addition to what the doctors feel is safest,(and I now feel that none of them think I could survive plasmapheresis, it depends on:

- Which one actually targets my specific auto-antibodies that attack the calcium channels
- Which one is least likely to cause anaphylaxis
- Which one has an amount of fluid that my body could handle without getting into pulmonary edema

Maybe I should start a thread on IVIG vs. RTX and all of these "sledgehammer options" to not detract this thread in case it is the wrong place (although it seems to fit in here?) I cannot figure out which is better for wiping out auto-antibodies- IVIG or RTX- with the other two big guns being plasmapheresis and other immunosuppressants.

They all seem like sledgehammer options that a year ago I would not have considered but now that I have a more specific grasp of my problem, it might take sledgehammer to knock it out. Other approaches like anti-virals, etc, did not work for me. I have nothing against them and know they work for a certain sub-group, but I am definitely in the auto-immune group.

I am not an expert on any of these therapies but you do have testing that your Drs can utilize to help you make the best decision with regard to treatment.

You have antibodies thay many are not familiar with here and all i know is that ME/CFS in its serious form is extremely scary.

These therapies have been used for many conditions with success.

Listen to your Drs and be sure to ask them all the questions you want answers to before deciding on a therapy.

 

[msf]

I'm not sure that rituximab is a sledgehammer.... It seems to me that it's the right tool for the job at least for a subset of people - until the researchers figure out some way of stopping the auto-antibodies from returning for good. I think I'd choose it over IVIG, if indeed I ever had/have that choice!

As Justin 30 said, it most definitely is a sledgehammer, if a very effective one going by the available evidence. The very fact that it works for several different conditions suggests that it is a sledgehammer, unless you believe that ME, lymphoma and RA all have the same underlying cause.

 

[msf]

Am curious re: the two above posts (@Justin30 and @daisybell) why RTX is more of a sledgehammer vs. IVIG? I do not know the answer and am asking in complete seriousness b/c I may end up in the position of choosing.

It will ultimately depend on what my doctors recommend and what my insurance will authorize. I have another appt and test before anything is decided (so earliest would be in May where we really discuss the options.)

For me, in addition to what the doctors feel is safest,(and I now feel that none of them think I could survive plasmapheresis, it depends on:

- Which one actually targets my specific auto-antibodies that attack the calcium channels
- Which one is least likely to cause anaphylaxis
- Which one has an amount of fluid that my body could handle without getting into pulmonary edema

Maybe I should start a thread on IVIG vs. RTX and all of these "sledgehammer options" to not detract this thread in case it is the wrong place (although it seems to fit in here?) I cannot figure out which is better for wiping out auto-antibodies- IVIG or RTX- with the other two big guns being plasmapheresis and other immunosuppressants.

They all seem like sledgehammer options that a year ago I would not have considered but now that I have a more specific grasp of my problem, it might take sledgehammer to knock it out. Other approaches like anti-virals, etc, did not work for me. I have nothing against them and know they work for a certain sub-group, but I am definitely in the auto-immune group.

I do not know the answer to most of your questions, but I think the sledgehammer analogy is more appropriate for Rituximab than IVIG, in that Rituximab ´hits´ something (the B cells). I believe Prof. Edwards has said that the mechanism by which IVIG seems to work in autoimmune diseases is not known.

 

[Gingergrrl]

The very fact that it works for several different conditions suggests that it is a sledgehammer, unless you believe that ME, lymphoma and RA all have the same underlying cause.

I believe Prof. Edwards has said that the mechanism by which IVIG seems to work in autoimmune diseases is not known.

I agree RTX is a sledgehammer approach and that it works for many conditions with different underlying causes. And Dr. Edwards definitely did say that the way that IVIG works in autoimmune diseases is unknown. But IVIG still seems like a sledgehammer approach to me b/c it also is used to treat such a variety of conditions from immune deficiency to auto-antibodies, etc, without even really knowing the mechanism (vs. with RTX, we know that it depletes the B cells.) Does this make sense? Am still trying to grasp it all myself.

 

[justy]

I agree RTX is a sledgehammer approach and that it works for many conditions with different underlying causes. And Dr. Edwards definitely did say that the way that IVIG works in autoimmune diseases is unknown. But IVIG still seems like a sledgehammer approach to me b/c it also is used to treat such a variety of conditions from immune deficiency to auto-antibodies, etc, without even really knowing the mechanism (vs. with RTX, we know that it depletes the B cells.) Does this make sense? Am still trying to grasp it all myself.

I see the extremely difficult dilemma you are in.

IVIG could push out the autoantibodies, making you feel better, BUT with the possible viral infections it could cause a massive herxheimer type reaction as the GG runs round the body mopping up infections etc (this happened to me when my low dose of SUB Q GG was a little too high and I had a three week herx from hell). You also have the added problem of the very real possibility of ANA to the pooled blood of 20,000 people. I have had atypical ana to low dose of this, but not so bad that I wouldn't carry on.

Ritux - may wipe out your autoantibodies and make you better - great news, however what effect would this have on the viral infections your body cant get rid of - in the short term? in the long term. Then you also have the possibility of ANA. I don't know what the risk is like for Ritux with MCAS.

I have heard that IVIG has been used in cases of Mastocytosis...could your Drs run this past Dr Afrin to get his opinion?

sorry to go off topic so much! Right now I feel so sick and the problems are piling up on top of each other that I would happily let someone hit me over the head with a sledgehammer if I thought it would help!

 

[daisybell]

@justy I think I have heard stories of people having reactions to IVIG due to the fact that there are antibodies pooled from such a large number of people. I would be very interested to know if in fact the risk of a bad reaction is lower with rituximab than IVIG. @Jonathan Edwards are you able to comment on this?

 

[Gingergrrl]

I see the extremely difficult dilemma you are in.

Thanks @justy and at the moment, none of these treatments have actually been offered to me and I need to have one more test (EMG and nerve conduction study) first and have my new local doc consult with my MCAS doc and the autonomic neuro up north who actually discovered the antibodies.

He said IVIG, immunosuppressants or plasmapheresis but then deferred it to the local doc in my area. The local doc is very concerned that I could have a true anaphylaxis reaction and said, "I am not going to rush into a treatment out of desperation that could hurt you... I do not want to seem mean, but I do not want to hurt you." I appreciated this very much but am so truly desperate now to improve my breathing and lung weakness, I am very close to not caring if the treatment kills me to put an end to this suffering.

IVIG could push out the autoantibodies, making you feel better, BUT with the possible viral infections it could cause a massive herxheimer type reaction as the GG runs round the body mopping up infections etc (this happened to me when my low dose of SUB Q GG was a little too high and I had a three week herx from hell). You also have the added problem of the very real possibility of ANA to the pooled blood of 20,000 people. I have had atypical ana to low dose of this, but not so bad that I wouldn't carry on.

I also have the added nonsense that one liter of IV saline/Magnesium gave me pulmonary edema so there is only so much fluid that I can handle in one sitting. IVIG has a high amount of fluid and protein which carries a risk of pulmonary edema and blood clots plus ANA risk. And with IVIG for autoimmune issues (my case) they like to start with an initial larger dose but I know this could not occur in my case. And the pre-meds for MCAS, would be extra volume to be taken into consideration.

Ritux - may wipe out your autoantibodies and make you better - great news, however what effect would this have on the viral infections your body cant get rid of - in the short term? in the long term. Then you also have the possibility of ANA. I don't know what the risk is like for Ritux with MCAS.

RTX had not been offered to me at all by the docs up north or my new local doc and I am just inquiring for my own knowledge. My concern is that I am still unclear if my particular auto-antibody is in the B-cells b/c if it is somewhere else, I could end up doing the treatment for nothing. And the ANA risk is very high for someone like me with RTX. And the question of it making the infections worse concerns me. I test IgM+ for EBV, VZV, etc, even though I have no current symptoms of them and completely on the autoimmune side with crazy allergic reactions.

I have heard that IVIG has been used in cases of Mastocytosis...could your Drs run this past Dr Afrin to get his opinion?

It has and my MCAS doc has 20-30 MCAS patients on it. He said Gamunex or Gammaguard are the only ones he would recommend for someone with MCAS (this is his opinion and I have no idea what Dr. Afrin would say.)

sorry to go off topic so much! Right now I feel so sick and the problems are piling up on top of each other that I would happily let someone hit me over the head with a sledgehammer if I thought it would help!

Not off topic to me, and I am ready to be hit over the head with a sledgehammer, too, and almost 4 AM here. Sorry to the original poster if we went off topic but I really love the sledgehammer concept and trying to apply it to our individual cases.

 

[Jonathan Edwards]

@justy I think I have heard stories of people having reactions to IVIG due to the fact that there are antibodies pooled from such a large number of people. I would be very interested to know if in fact the risk of a bad reaction is lower with rituximab than IVIG. @Jonathan Edwards are you able to comment on this?

Yes I think the rate of reactions is lower with rituximab than Ig. Of the first hundred patients we gave rituximab only one had to stop it because of a reaction (rash). I have not treated many people with IVIG but my impression is that about one in five at least run into reaction problems.

 

[msf]

I agree RTX is a sledgehammer approach and that it works for many conditions with different underlying causes. And Dr. Edwards definitely did say that the way that IVIG works in autoimmune diseases is unknown. But IVIG still seems like a sledgehammer approach to me b/c it also is used to treat such a variety of conditions from immune deficiency to auto-antibodies, etc, without even really knowing the mechanism (vs. with RTX, we know that it depletes the B cells.) Does this make sense? Am still trying to grasp it all myself.

Yes, that makes sense. I think IVIG might be a sledgehammer in the sense Justy talked about above, although if it only targets pathogens then it might be a useful sledgehammer/big nutcracker! When I talked about a sledgehammer I was really thinking (at least in the case of Rituximab and antibiotics) of something that hits ´good´ B cells and ´good´ bacteria as well as bad ones.

 

[Gingergrrl]

Yes I think the rate of reactions is lower with rituximab than Ig. Of the first hundred patients we gave rituximab only one had to stop it because of a reaction (rash). I have not treated many people with IVIG but my impression is that about one in five at least run into reaction problems.

Do you mean anaphylaxis reactions or all reactions? (like pulmonary edema, blood clots, infections, etc)

Yes, that makes sense. I think IVIG might be a sledgehammer in the sense Justy talked about above, although if it only targets pathogens then it might be a useful sledgehammer/big nutcracker! When I talked about a sledgehammer I was really thinking (at least in the case of Rituximab and antibiotics) of something that hits ´good´ B cells and ´good´ bacteria as well as bad ones.

Thanks @msf, and I am not sure if IVIG just targets pathogens b/c I think it also targets autoimmune diseases or auto-antibodies which would be the purpose in my case. I thought you meant sledgehammer as one of the "big guns" that are the most hardcore as far as what treatment entails and also level of risk/side effects.

But I think now you meant it as something that can also kill good cells or bacteria? So would immunosuppressants or chemotherapy be more what you meant? I know immunosuppressants were one of the first things mentioned to me but then retracted after the original doctor saw which antibody I had b/c of the cancer risk it correlates with.

I wish I knew which treatment was going to be offered to me so I could be more specific. Would plasmapheresis be in this category? All the doctors seem to say I would not survive it b/c it involves installing a port and completely exchanging plasma for donor plasma or synthetic (albumin or other names I am forgetting) plus it involves chemicals to keep the blood from clotting while in the machine. It seems to have too many parts I could be allergic to (although in my mind it seems like the greatest chance to actually remove the antibody.)

IVIG seems random in that it would have the correct antibody to replace mine with and RTX I am unclear if my antibody is actually in the B-cells vs. somewhere else in body? I want to make as informed a choice as possible but also know it is doubtful what will be offered to me b/c of my MCAS. I feel I am not smart enough to understand all this but am going to keep trying my hardest. Am going to do one of the sledgehammer treatments if offered to me. This would have been unthinkable even one year ago but I have progressed where not a lot to lose and it feels worth the risk to me whereas a year ago it did not.

Sorry I type a lot and didn't mean for you (msf) to answer all of this! Am just thinking out loud.

 

[Jonathan Edwards]

Do you mean anaphylaxis reactions or all reactions? (like pulmonary edema, blood clots, infections, etc)

I was meaning allergic or immune reactions to the drug within hours. Most reactions with IVIG are a nuisance rather than dangerous, but they can make continued treatment difficult. With proper monintring infusion reactions with rituximab are rare. However, I suspect that a sort of sterile pneumonia can occur within a week or so of infusion and it can be dangerous. Increased rates of infection for certain viruses do occur with rituximab but the only serious one I know of (JC virus) is something like one in twenty thousand cases.

 

[rosie26]

However, I suspect that a sort of sterile pneumonia can occur within a week or so of infusion and it can be dangerous

Would the danger of sterile pneumonia be fungal? Thrush through the respiratory tract?

 

[Gingergrrl]

@Jonathan Edwards I believe I may have asked you one or both of these questions before and apologize if that is the case and also apologize if they are stupid or basic questions.

- Can someone attempt IVIG and RTX or are they mutually exclusive? I do not mean try them at the exact same time of course, but if someone tried one and it did not work or not tolerated for any reason, could they still try the other in the future? I know you once posted this was not the case with IVIG and plasmapheresis b/c one is putting something in, and then the other is then taking it out, so you would have to choose. But with IVIG and RTX, would you have to choose?

- Also, are all auto-antibodies primarily in the B-cells? Meaning if someone with ME/CFS had a presumed auto-antibody vs. someone like me who has two known auto-antibodies on blood test, in both cases, are they in the B-cells and this is a known fact or could they be somewhere else in the body so killing the B-cells wouldn't destroy them?

 

[Jonathan Edwards]

Would the danger of sterile pneumonia be fungal? Thrush through the respiratory tract?

When I say sterile I mean not associated with any infection - some sort of immune reaction.

 

[Jonathan Edwards]

@Jonathan Edwards I believe I may have asked you one or both of these questions before and apologize if that is the case and also apologize if they are stupid or basic questions.

- Can someone attempt IVIG and RTX or are they mutually exclusive? I do not mean try them at the exact same time of course, but if someone tried one and it did not work or not tolerated for any reason, could they still try the other in the future? I know you once posted this was not the case with IVIG and plasmapheresis b/c one is putting something in, and then the other is then taking it out, so you would have to choose. But with IVIG and RTX, would you have to choose?

- Also, are all auto-antibodies primarily in the B-cells? Meaning if someone with ME/CFS had a presumed auto-antibody vs. someone like me who has two known auto-antibodies on blood test, in both cases, are they in the B-cells and this is a known fact or could they be somewhere else in the body so killing the B-cells wouldn't destroy them?

All antibodies come from B cells - that is what B cells do, and nothing else. But rituximab only kills B cells that are expanding in early life. The majority of antibody is made by old mature B cells, that are called plasma cells and which rituximab does not kill directly - they have to die off over months.

IVIG and rituximab could be used in combination but it would be pretty complicated and inefficient.

 

[justy]

When I say sterile I mean not associated with any infection - some sort of immune reaction.

This sort of 'sterile infection' is seen in MCAS patients - it had been driving my Drs nuts trying to work out why I looked like I had lung infections, but didn't actually have evidence of them. Glad I could be of service in working it out for them

 

[Gingergrrl]

All antibodies come from B cells - that is what B cells do, and nothing else. But rituximab only kills B cells that are expanding in early life. The majority of antibody is made by old mature B cells, that are called plasma cells and which rituximab does not kill directly - they have to die off over months.

Thank you and I will try to remember this without asking again. So, all auto-antibodies come from B-cells no matter what they are. This makes it seem like RTX could be the right treatment for me, more than I had thought?

IVIG and rituximab could be used in combination but it would be pretty complicated and inefficient.

I was just curious if they could be used together (I don't mean at the exact same time) more that they do not cancel each other out in some way. I spoke to someone from PR who has done this (after I asked the question) so I know it is possible although pretty rare.

This sort of 'sterile infection' is seen in MCAS patients - it had been driving my Drs nuts trying to work out why I looked like I had lung infections, but didn't actually have evidence of them. Glad I could be of service in working it out for them

I had not heard of this before. Someone was explaining "sterile cell death" to me and is this similar to "sterile pneumonia?" Does this just mean you have pneumonia but no signs of infection causing it? Why is this more common or higher risk in MCAS patients? Am asking @Jonathan Edwards or @justy or anyone who knows! Thanks in advance!

 

[rosie26]

This sort of 'sterile infection' is seen in MCAS patients - it had been driving my Drs nuts trying to work out why I looked like I had lung infections, but didn't actually have evidence of them. Glad I could be of service in working it out for them

I think this is what I am getting with my lungs. It would explain the oral thrush that I have had bouts of in the last year. And also, no wonder I had such a huge negative reaction after taking antibiotics last year.

 

[justy]

Thank you and I will try to remember this without asking again. So, all auto-antibodies come from B-cells no matter what they are. This makes it seem like RTX could be the right treatment for me, more than I had thought?



I was just curious if they could be used together (I don't mean at the exact same time) more that they do not cancel each other out in some way. I spoke to someone from PR who has done this (after I asked the question) so I know it is possible although pretty rare.



I had not heard of this before. Someone was explaining "sterile cell death" to me and is this similar to "sterile pneumonia?" Does this just mean you have pneumonia but no signs of infection causing it? Why is this more common or higher risk in MCAS patients? Am asking @Jonathan Edwards or @justy or anyone who knows! Thanks in advance!

Dr Afrin talks about this more than once in his book - I had no idea until I read this. He says many of his patients keep being given antibitoics for infections - often lung or bladder, but they actually have a sterile infection caused by the MCAS - inflammation driven I think. Not sure which section he discusses it in, you'll know it when you see it though.

 

[Gingergrrl]

The majority of antibody is made by old mature B cells, that are called plasma cells and which rituximab does not kill directly - they have to die off over months.

In theory then, assuming that the patient could tolerate it, would plasmapheresis and RTX together be the best combination to get the mature B cells in the plasma and the already existing auto-antibodies? I know this is probably not realistic, but just curious if I am grasping the concept.

Increased rates of infection for certain viruses do occur with rituximab but the only serious one I know of (JC virus) is something like one in twenty thousand cases.

Is JC virus the "Jakob Creutzfeldt" virus in the US or something else? It seems that this virus (JC or Jakob Creutzfeldt) is a risk with IVIG and it sounds like it is a potential risk with RTX, too?