A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
Mark Berry presents the first in a series of articles on the 11th Invest in ME International ME Conference in London ...
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rituximab questions

Discussion in 'Rituximab: News and Research' started by jaybee00, Jul 31, 2016.

  1. jaybee00

    jaybee00

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    Hello,

    Had some more questions on rituximab--appreciate any assistance. Also please feel free to point out earlier posts if these issues have already been addressed.

    1. Why the infusion on day 14? Does the initial infusion miss some of the B cells?

    2. The follow on infusion on Month 3, 6, 9. etc. These are to keep depleting the B cells? Can this eventually be spaced out to once per year or twice per year?

    3. What happens to the good antibodies that we have after B cell depletion ..i.e. antibodies to vaccines etc.?

    4. There are several case reports of colitis following RTX therapy. Has this occurred in any CFS patients? Thoughts?

    http://www.gastroenterologyandhepat...ulminant-colitis-following-rituximab-therapy/

    Thank you.
     
  2. Hip

    Hip Senior Member

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    I think these questions are probably answered somewhere on the forum. I'd suggest using a Google search directed at the forum: place the following text in the Google search box in order to do this:
    Code:
    site:phoenixrising.me 
     
    Last edited: Jul 31, 2016
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  3. greeneagledown

    greeneagledown Senior Member

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    First, some disclaimers: 1) The informal advice on this site is no substitute for a medical opinion from a doctor; and 2) Rituxan is not yet proven to be safe and effective in CFS.

    The 2nd infusion at day 15 is supposed to increase b-cell depletion and/or make it last longer. It may or may not be truly necessary, but it's what's almost always done in all diseases where Rituxan is used as a treatment. Probably best to stick to what has been clinically tested.

    The maintenance infusions are to maintain B-cell depletion. One infusion twice a year would probably not be sufficient to maintain depletion, and one infusion once a year DEFINITELY would not be sufficient. At some point, patients need to take an extended break (probably at least a year) from infusions to let helpful antibody levels build back up. It's not a settled matter as to how long patients can get infusions before taking this break, but doctors can measure your normal antibody levels to try to figure out when you need to take a break from Rituxan. In RA, some patients get infusions regularly for up to 5 year before taking a break, although that may be pushing it. The hope is that for maybe a quarter of CFS patients, just 6 infusions will be enough to cause extended remission.

    For reasons that are unclear, typically levels of normal or "good" antibodies fall much more slowly than autoantibody levels during use of Rituxan. Plasma-B cells that create autoantibodies tend to have much shorter lifespans than plasma-B cells that create normal antibodies. That being said, use of Rituxan does tend to reduce normal antibody levels in the long run.

    I'm not a doctor, this is not medical advice, etc. etc.
     
  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Not a bad stab greeneagledown, but maybe as the person who invented this regimen for autoimmune disease I might jump in here! I am not going to give advice either but can give the facts.

    The infusion at day 14 is a hang over from a protocol that I set up in 1999, designed to allow convenient co-administration with cyclophosphamide and has never got change because the drug company could not bother to find out what was the best regimen. We gave up using 14 days in about 2005 but it got into the license for autoimmune diseases so most people use it. The simple fact is that the regimen started off with four infusions and we condensed them to two double infusions. We still have no idea whether or not one is enough. Two infusions at half dose seem to give slightly less good results in RA but one full dose infusion may be perfectly good. The only reason for two doses is that nobody has worked out if one will do. The 14 day gap makes no sense and at UCH we used a week - simply for convenience of booking the clinic.

    To keep B cells depleted you need to give rituximab once every six months in most people. A few people get B cells back a t 5 months so the Norwegian idea of topping up at 3 months is clever in the sense of making sure nobody gets B cells back, but may be much more often than needed. The reason to stick to it is simply that it is the regimen in the phase 2 trial and until we know the drug actually works in ME/CFS it is probably unhelpful to play around with the schedule. In other autoimmune diseases about half patients only need rituximab once a year or even less often so the time B cells come back is not necessarily crucial, but it is very rare to see relapse while B cells are depleted. So generally speaking, in a disease where rituximab works, the optimum is to give it as often as that person needs, which might be six monthly or in some cases once every two years. But in ME/CFS things might be different and the Norweginas went for a longer period of depletion - we do not now if this is necessary but it is what is being tried at present.

    Good antibodies by and large do not go down much after rituximab. But after several courses they go down to a significant extent in a proportion of people. If they fall to well below normal then the usual practice is to stop rituximab at least for a while and maybe re-vaccinate.Not many people with RA need that break but in ME we do not as yet know.

    Colitis after rituximab is as far as I know very rare and may be conincidence. Patients with lymphoma receiving rituximab (as in the case report) may have other reasons to get colitis - the lymphoma may be in the gut wall and killing it may cause damage there for instance. We predicted that rituximab would be no use in ulcerative colitis and that is the case, but there seems little evidence for it getting worse so the cases of colitis after rituximab may have nothing to do with ulcerative colitis. I would still be a bit cautious about using rituximab in someone who already has UC, because rituximab does seem to be able to exacerbate other T cell drive illnesses like psoriasis.
     
  5. jaybee00

    jaybee00

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    Thanks so much for the helpful reply.

    I also meant to ask about neutropenia. Is this common? If it happens, does it require hospitalization or does it resolve on its own?

    Thanks again.
     
  6. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Really interesting insight Jonathan! I was pondering of some of those things.
     
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  7. Gingergrrl

    Gingergrrl Senior Member

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    Since we are asking questions, can RTX cause a headache similar to that of IVIG?
     
  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Neutropenia is uncommon. Maybe in one case in fifty. As far as I am aware it is nearly always mild enough not to require hospitalisation - or at least is transient and without major problems.

    I have not come across rituximab causing headache. Any infusion that causes a stress reaction might produce a headache - it is the sort of thing that commonly occurs as a side effect of placebos. I don't think there is any specific risk of headache with IVIG either.
     
  9. Gingergrrl

    Gingergrrl Senior Member

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    Headache is the #1 side effect of IVIG that every doctor warned me about b/c it is such a thick substance and can cause swelling or inflammation of the brain, even aseptic meningitis. They give Tylenol and steroid as a pre-med partially for this reason.

    I did not develop the headache until two days after the infusion was done so thought I was in the clear but doctors told me this was common too. They said it can take 2-3 wks to resolve and may need IV fluid or IV steroids.

    Don't want to get this off track, and it sounds like RTX does not cause the IVIG headache, but just wanted to post it is a very real phenomenon that is unrelated to stress and I am not a person who regularly gets headaches and have never had a migraine in my life (but those who do are at higher risk of it with IVIG per doctors and the literature.)
     
  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I was talking of stress in the physiological sense of a shift in blood pressure etc. That can be set off by anything that triggers immune mediators like cytokines (the reason for the steroids and tylenol). IVIG may well do that quite often because of interaction with your own Ig and cells. Rituximab can produce such a reaction if given too fast but as long as infusion is monitored carefully I have not come across headache later.

    I don't think the effect of IVIG has anything to do with it being 'thick' - it is after all exactly the same stuff as you already have in your blood - Ig - but doctors often use poetic language to try to give simple explanations! If it is given in huge amounts very fast it might increase plasma viscosity but I doubt this ever goes above normal range.
     
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  11. Gingergrrl

    Gingergrrl Senior Member

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    Thanks and I learned that my infusion speed was too fast and this increased the headache risk. IVIG also can increase blood viscosity (I have no idea re: RTX) and they often thin it out with saline or D5 Dextrose solution (depending on which brand of IVIG).

    If I'd had fever or blurry vision etc would be at ER now b/c this headache has lasted 8-9 days. They still might have me go tomorrow and can't do next IVIG until headache gone for one week. The viscosity also can be hard on the kidneys (but I have been okay in this regard).

    Am interested to hear comparison to RTX and it sounds like it also requires a very slow infusion speed which is good to know (for someone like me) but maybe not for everyone.
     
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  12. Jill

    Jill Senior Member

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    I too got a horrendous headache about a day after IVGG. I was part of prof dwyers trial back in early 90s in Sydney . Nobody warned me of this and I spent about 2 days throwing up with a terrible headache at a dear elderly couples house who my family knew in Sydney . I remember them both with such fondness as it was so awful to be staying with them and being so ill!!! In the long run it didn't help me .
     
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  13. Gingergrrl

    Gingergrrl Senior Member

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    @Jill Am sorry to hear that you also went through this and for me the headache did not start for at least 24 hours (or maybe even closer to 48 hours?) until after the IVIG. It was not instant and I was really shocked that it could be so delayed and so severe.
     
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  14. Jill

    Jill Senior Member

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    Yes it was delayed for me too. I,m sure it was related to the treatment, although when we phoned the investigators sthey seemed unconvinced.
     
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  15. msf

    msf Senior Member

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    I have a question: Is there a possibility that Ritux works in ME by killing some deficient immune cells that arenĀ“t doing their job? Would the response time correspond to the maturation of new, efficient cells?

    I know nothing about how the immune system regenerates itself, so be gentle.
     
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  16. Kalliope

    Kalliope Senior Member

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    I hope it is ok to ask another question on Rituximab here?

    I've seen from two different places warnings about the RituxME-trial that one can't trust its results when it gets published because Rituximab has so many side-effects those who get infusions with the medicine will know they are not getting placebo.

    The criticism is from "biopsychosocial" hold.

    Has this been a valid argument towards previous placebo-controlled trials on Rituximab?

    @Jonathan Edwards (or others) - any input?
     
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  17. eljefe19

    eljefe19

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    According to Dr Kaufman at OMI there's virtually no side effects from Rituximab. I trust him.
     
  18. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    There are normally no side effects of note from rituximab. There may be telltale symptoms of the drug having its effect in a proportion of people but in other blinded trials of rituximab this has not been a significant problem. This is a reasonable concern and one that has been discussed. After all it is because of failed blinding that PACE and all the other similar trials are no good at all. However, there are reasons to think that the majority of patients in the trial will really not have been able to tell whether they had drug or not. I think the results will be interpretable.
     
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  19. Kalliope

    Kalliope Senior Member

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    Many thanks! How wonderful to be able to ask one of the experts in the field directly.
     
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  20. Jesse2233

    Jesse2233 Senior Member

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    @Jonathan Edwards

    Is there any risk or wisdom in administering anti-viral drugs alongside Rituximab? The rational being to ward off opportunistic infections that might occur with diminished B-cells.

    And if one has high IgG titers for a given virus (such as coxsackie B4) is there a risk of the latent virus reactivating while receiving Rituximab?

    Thank you!
     

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