My ritux experience so far

[Murph]

Any updates @Benji? I'm hoping!

 

[Benji]

I'm hoping too. I am a little better today, but not anywhere around when I had response. Yet. We'll see.
I will be very happy when I can say that I am better again, and won't hesitate telling.

 

[Wonkmonk]

@Benji Is there any hint/information in Norway how the recently unblinded Ritux trial turned out? Still ~33% responders, ~33% partial responders, ~33% nonresponders?

 

[Benji]

I have not heard anything lately.

Before summer? There was one of the center in a News article, that they had 7-8 people remarkably improving, out of a total of 32 (16 placebo, 16 ritux)

It is quite quiet about the ritux study in media, but much ME pubiisity, where Wyller and Vogt and other people criticizing ME association, ME sick people, for not knowing their own best and misguiding new patients, that people can recover with CBT and the biomedical way is old fashioned, and LP og CBT is the new modern thing that will cure everyone. Puh.
Ritux study will come later. Looking forward to it!

 

[Wonkmonk]

Thanks for explaining. I am also looking into Rituximab, mainly because I read a lot about it in the past weeks and relatives talked to some doctors who use it and it seems to be less risky than I initially thought.

I had some very good improvements on antivirals, but I'm still unable to work or have social activity, so I am looking into further options now and Rituximab seems to be the most promising.

 

[Benji]

Thanks for explaining. I am also looking into Rituximab, mainly because I read a lot about it in the past weeks and relatives talked to some doctors who use it and it seems to be less risky than I initially thought.

I had some very good improvements on antivirals, but I'm still unable to work or have social activity, so I am looking into further options now and Rituximab seems to be the most promising.

That is so interesting. For many, rituximab helps a lot, but don't get 100 % healthy.
So antivirals sounds very interesting to battle the "rest-disease". I don't how what my case will show in the end.
I still have no response (yet), after the infusion late may.
I have my next and last infusion for mid-December. I kind of going my own way in this.

 

[Wonkmonk]

If I try Rituximab, I plan to continue antiviral treatment. An Oncologist stated to my sister that it's no problem to take high-dose Valacyclovir while doing Rituximab. In fact many patients need it, because they get herpes virus outbreaks after Ritux.

I plan to continue everything that has helped in the past and hope that collectively it will one day lift me up to a state in which I can work again.

So far that's Nimodipine plus Valacyclovir plus Probenecid (which I added recently per Dr Lerner's protocol and it seems to help a bit).

 

[Wonkmonk]

For many, rituximab helps a lot, but don't get 100 % healthy.

My speculation was that at least for some patients, EBV is directly responsible for their illness. Perhaps mediated by some process in the B-cells, but EBV is the main cause and if you fight it, you get better.

Rituximab destroys EBV's main reservoir, but only few patients clear EBV after Rituximab treatment, probably because not all B-cells are destroyed or because EBV has other reservoirs in the body than the B-cells and returns once Ritux treatment stops.

But if you continue high-dose antivirals during the Rituximab, one should be able to stop any remaining EBV virus from reinfecting new B-cells and it should be possible to kill EBV entirely. In fact, a few patients have cleared EBV after Rituximab and one study suggests long-term administration of valacyclovir can also lead to EBV vanishing from the body.

So it might be worth trying if Valacyclovir plus Rituximab entirely cures patients or at least improves response. At least that's my latest layman's speculation.

But probably Prof. Edwards is soon going to jump in again and tell me it doesn't work that way

 

[frederic83]

But if you continue high-dose antivirals during the Rituximab, one should be able to stop any remaining EBV virus from reinfecting new B-cells and it should be possible to kill EBV entirely. In fact, a few patients have cleared EBV after Rituximab and one study suggests long-term administration of valacyclovir can also lead to EBV vanishing from the body.

I read somewhere on PR, a few years ago, that a canadian or US doctor did a informal trial of Ritux + antiviral to clear as much virus as possible. I don't know if the trial was conclusive

 

[Gingergrrl]

I still have no response (yet), after the infusion late may.
I have my next and last infusion for mid-December. I kind of going my own way in this.

Good luck with your next infusion and thank you for keeping us posted. My next ritux infusion will be on 10/31. It is my first maintenance infusion and #3 (so far).

If I try Rituximab, I plan to continue antiviral treatment. An Oncologist stated to my sister that it's no problem to take high-dose Valacyclovir while doing Rituximab. In fact many patients need it, because they get herpes virus outbreaks after Ritux.

My understanding is also that is safe for patients to take anti-virals while doing Rituximab. In my case, anti-virals did not help me (and I have not taken them since early 2015). But if they were helping me, I am certain that my doctor would have me continue w/them.

I read somewhere on PR, a few years ago, that a canadian or US doctor did a informal trial of Ritux + antiviral to clear as much virus as possible. I don't know if the trial was conclusive

I don't know anything about the Canadian study but my understanding was that OMF was going to conduct a study a few years back with Valcyte & Rituximab but it never occurred due to lack of funding. (Hoping someone will correct me if I am wrong on this).

 

[Wonkmonk]

OMF was going to conduct a study a few years back with Valcyte & Rituximab but it never occurred due to lack of funding.

If one assumes EBV causes CFS in some patients, it would be reasonable to try this. Take Dr Lerner's theory for instance: He says CFS in some patients is caused by continuing partial replication of the herpesvirus and the incomplete herpesvirus particles infect cells and cause mayhem all over the place (at least very simplified, hope I got it right).

He wrote that Valtrex helps, because long-term treatment reduces the number of EBV-infected B-cells and therefore the amount of incomplete herpesvirus particles that cause disease. That takes very long, because B-cells have a half-life of several months, so for the infected ones to be replaced by healthy ones it takes a lot of time and recovery is very slow.

If this theory is correct, or at least if the hypothesis that EBV does something that causes CFS symptoms is correct, and if reducing the number of EBV-infected cells in the body is responsible for the recovery under Valtrex, then Rituximab may (a) be a short-cut to speed up recovery, and (b) help kill as many EBV-infected B cells as possible, or in fact, in combination with Valtrex even remove EBV entirely from the body.

Too bad that study didn't happen.

 

[frederic83]

I don't know anything about the Canadian study but my understanding was that OMF was going to conduct a study a few years back with Valcyte & Rituximab but it never occurred due to lack of funding. (Hoping someone will correct me if I am wrong on this).

That's probably this trial I heard about.

 

[Jesse2233]

That's probably this trial I heard about.

Believe it was OMI, not OMF

 

[Wonkmonk]

f this theory is correct, or at least if the hypothesis that EBV does something that causes CFS symptoms is correct, and if reducing the number of EBV-infected cells in the body is responsible for the recovery under Valtrex, then Rituximab may (a) be a short-cut to speed up recovery, and (b) help kill as many EBV-infected B cells as possible, or in fact, in combination with Valtrex even remove EBV entirely from the body.

But let me add: The potential downside is, if my CFS is not caused by EBV, but by some other virus, then killing the B-cells is counterproductive, because you need them to fight that other virus. It is by no means certain that Valtrex and Valcyte help some patients because they stop viral replication. Immune modulation might be another mechanism, or keeping the herpes virus at bay might set free immune system capability to fight some other virus that is actually responsible for CFS symptoms.

Rituximab has a very long half-life. An oncologist who often uses it told my sister that after a single infusion, it takes 5 months until it is out of the body and it will take some more months until B-cell counts are back to normal. So if one starts Rituximab, one has to be aware that it will weaken the immune system for several months, and any negative effects it may have may be signficant and lasting.

 

[frederic83]

Rituximab has a very long half-life. An oncologist who often uses it told my sister that after a single infusion, it takes 5 months until it is out of the body and it will take some more months until B-cell counts are back to normal. So if one starts Rituximab, one has to be aware that it will weaken the immune system for several months, and any negative effects it may have may be signficant and lasting.

I read on Wikipedia that the half life of Rituximab is between 30 to 400 hours (varies by dose and length of treatment)

 

[Wonkmonk]

I read on Wikipedia that the half life of Rituximab is between 30 to 400 hours (varies by dose and length of treatment)

That would be significantly less than the Oncologist said. confusing. But even then, you have a half life of two weeks (I'd have to get the highest dose, 1000mg), so it takes about 2 months until the antibodies are out and then a few months until your B-cells come back.

So whoever is right about the half life, the effects will be felt for several months.

 

[Gingergrrl]

Believe it was OMI, not OMF

You are right, it was OMI (not OMF) that was going to do that study. Sorry I was confused!

But let me add: The potential downside is, if my CFS is not caused by EBV, but by some other virus, then killing the B-cells is counterproductive, because you need them to fight that other virus.

My understanding (which again could be wrong!) is that the memory B cells that fight viruses/pathogens are in the plasma (or somewhere untouchable to Rituximab) which is why we do not have to get re-vaccinated for anything after having Ritux and can still fight future pathogens that we encounter. I hope someone can explain this better than I can! (And this would also apply to Rituximab for other medical conditions, not just for ME/CFS). Although I'd assume if Ritux is done as chemo for cancer with multiple other chemos or immunosuppressants, you are more at risk than just having Ritux as a monotherapy for an autoimmune condition.

Rituximab has a very long half-life. An oncologist who often uses it told my sister that after a single infusion, it takes 5 months until it is out of the body and it will take some more months until B-cell counts are back to normal.

I read on Wikipedia that the half life of Rituximab is between 30 to 400 hours

That would be significantly less than the Oncologist said. confusing.

I agree, that is confusing (the three quotes above) re: half-life and my guess is that perhaps the actual Ritux infusion leaves the body within 30 to 400 hours (so if you were allergic to it, it is eventually gone) vs. the effects that is has to keep B cells at zero remains for up to six months (or longer)? My 2nd Ritux infusion was Aug 1st and my B cells are still at zero almost three months later.

 

[Wonkmonk]

My understanding (which again could be wrong!) is that the memory B cells that fight viruses/pathogens are in the plasma (or somewhere untouchable to Rituximab) which is why we do not have to get re-vaccinated for anything after having Ritux and can still fight future pathogens that we encounter.

My understanding (which of course could also be wrong ) is that Rituximab attacks all the B-cells that are in the body at the time of the infusion (and the days thereafter), including memory B-cells, and is also effective at killing most of them, but new B-cells that are produced after the Rituximab effect wears off are the same B-cells as before, i.e. they have the same immunity as before, so you don't need new vaccinations because the new B-cells that are produced after Rituximab are just as effective as the old B-cells were that Rituximab destroyed. (huh, that was complicated, hope I don't confuse everyone).

But that being said, for the time during which Rituximab is active, you don't have the B-cells in your blood (or many fewer of them than you usually would have) and that's also why you are more susceptible to usual infections (common cold, flu etc.) during that time.

So that's my argument: there is an immunosuppressive effect of Rituximab and if it's not EBV and not autoantibodies, but instead it is another virus that causes the CFS, then Rituximab will make you less effective at fighting that virus for some time.

This might explain why some CFS patients got much worse after Rituximab. Maybe their CFS is caused by Coxsackie or some other virus and now they are killing their B-cells with Rituximab and get immunosuppressed and then they are even less able to keep Coxsackie at bay and everything gets worse.

 

[Gingergrrl]

My understanding (which of course could also be wrong ) is that Rituximab attacks all the B-cells that are in the body at the time of the infusion (and the days thereafter), including memory B-cells, and is also effective at killing most of them, but new B-cells that are produced after the Rituximab effect wears off are the same B-cells as before, i.e. they have the same immunity as before, so you don't need new vaccinations because the new B-cells that are produced after Rituximab are just as effective as the old B-cells were that Rituximab destroyed. (huh, that was complicated, hope I don't confuse everyone).

I was discussing this last night w/a friend of mine from another medical group (she has POTS and some overlap with me but also has several medical conditions that I do not have). She will possibly be having Rituximab for the rest of her life (vs. I am doing a series of six infusions over the course of one year). She had similar concerns as you re: immuno-suppression and spoke with her infusion nurse and she paraphrased her explanation (below):

"B-Cells are our 'memory' immune cells. When our bodies get a cold and fights it, the B-Cells keep a small copy of the virus and the DNA used to fight that virus. That way if that same virus is introduced into your system your body can fight it. Rituxan implants a chemical code into the cells that tells them that they need to commit suicide. It seems like a bad idea to kill the cells that remember how to fight basic things. In talking to my nurse she said that the bone marrow is what reproduces cells, so the memory is probably in the bone marrow more then the actual cells. So we're probably okay".

She used the word "probably" twice but it kinda reassured me that (hopefully?!) the memory is in the bone marrow and these are the B cells that survive?

Re: what you said about new B cells having the immunity, my understanding is that the B cells remain at zero for the entire year of treatment and that this is the goal (to keep them at zero) so it would have to be some other mechanism that continues to fight viruses, etc.

In Jan, I will not have had a cold, flu or traditional illness in five years. I did the first two Ritux infusions in July/Aug (now mid Oct) but I still have not gotten sick. I have been exposed to both my step-daughter and niece while they were sick (and my niece even had strep throat right before I was with her) but I did not catch it. I've been in restaurants, at hospitals, my infusion center, and regular public places but thus far, have not caught anything. But I continue to do IVIG so this might be protective. I am also extremely on the auto-immune side.

But that being said, for the time during which Rituximab is active, you don't have the B-cells in your blood (or many fewer of them than you usually would have) and that's also why you are more susceptible to usual infections (common cold, flu etc.) during that time.

It seems to be the case but my doctor said that he has not had any patients get sick after getting Ritux (including those who flew on an airplane immediately after the infusion)- which does not pertain to me and I have not been well enough to fly since mid 2013.

So that's my argument: there is an immunosuppressive effect of Rituximab and if it's not EBV and not autoantibodies, but instead it is another virus that causes the CFS, then Rituximab will make you less effective at fighting that virus for some time.

This doesn't match with what my doctor has said so far (or with people in another medical group that I belong to who have done Ritux long term) but maybe ME/CFS is different? I had very high IgM+ and early antigen (EA+) titers to EBV for about 3 yrs post-mono until they finally went negative. But after Ritux, my EBV did not re-activate (that I am aware of, but we have not re-tested it). One of my daughter's best friends has mono right now (I was never exposed to her directly) so I am concerned about this but nothing that I can do.

This might explain why some CFS patients got much worse after Rituximab. Maybe their CFS is caused by Coxsackie or some other virus and now they are killing their B-cells with Rituximab and get immunosuppressed and then they are even less able to keep Coxsackie at bay and everything gets worse.

I honestly have no idea! I tested positive twice for Coxsackie B4 and Echovirus 11 from ARUP lab, and I suspect most people test positive for both herpes and enterovirus titers, especially IgG+, but I have no statistics on that!

 

[Wonkmonk]

@Gingergrrl Thank you so much for your long explanation, that's very reassuring. Of course I know every case is special and yours is still special among the special cases, but the more I think about it, the more I come to the conclusion that Rituximab might be worth trying for me.