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Confused on Rituximab

Discussion in 'Rituximab: News and Research' started by cman89, Oct 22, 2014.

  1. cman89

    cman89 Senior Member

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    Something about the focus on rituximab in the CFS world is confusing me. as this drug is meant to target B cells, in effect, killing them off, why arent other immunomodulator/suppresant drugs given a focus alongside this one. I have not been following research on this drug and CFS, so forgive me, but why this drug, and not even some of the other drugs that target b cells, either ant cd20 drugs, or ones that work in another mechanism. Some of the MS drugs seem to have a likelyhood of co -success with CFS, at least based on mechanism of action. Why rituximab?
     
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  2. aimossy

    aimossy Senior Member

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  3. snowathlete

    snowathlete Not an ol' sleazebag

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    It's Rutiximab because some cancer doctors in Norway were treating patients with cancer who also had ME/CFS and they noticed that their ME/CFS got better on the drug. Rather than ignore this they then looked into it properly and did a trial on ME/CFS patients which appeared to show it works. Crowdfunding and a lot of hard work later and we are in phase 3 trials.

    In the future, I wouldn't be surprised if other similar drugs become better options for patients, but it requires will and funding on the part of governments really, and we still don't have that. Else it is slow and dependant on what a small numbers of researchers, charities and patients can manage.
     
    Last edited: Oct 22, 2014
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  4. cman89

    cman89 Senior Member

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    Was not aware of the Norwegian doctor connection. that clears some things up. Seemed a bit random to me.
     
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  5. Valentijn

    Valentijn The Diabolic Logic

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    Funding for biological research (especially biological treatments) regarding ME/CFS has been extremely sparse in the past decades. It's an extremely rare and fortunate thing that the Rituximab trials are happening at all.
     
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  6. wastwater

    wastwater Senior Member

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    I don't really know what im on about but what about anti cd40 dacetuzumab or lucatumumab what might that do
     
  7. A.B.

    A.B. Senior Member

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    Rituximab targets the CD20 protein, which is mainly found in B cells. CD40 is expressed by a variety of different cell types. That Rituximab works suggests the B cells are to blame for ME/CFS symptoms. At least that is the obvious explanation. From what is presently known it doesn't make sense to target anything else.
     
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  8. Jonathan Edwards

    Jonathan Edwards Senior Member

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    A big part of the answer is certainly that rituximab happens to have been tried and looks promising. But apart from that we are now in an era where 'immunosuppressant' or 'immunomodulator' have become more or less obsolete terms because we are in the business of targeting specific signalling molecules or cells for specific reasons based on understanding of disease mechanisms. Traditional immunomodulators like methotrexate are really pretty hopeless for most autoimmune diseases and are being replaced by things like TNF inhibitors, B cell depletors, IL-6 inhibitors or costimulation inhibitors. Anti-CD40 might get at costimulation (which is a good target in RA using abatacept) but my memory says that an anti-CD40 was tried and it had disastrous adverse effects in terms of platelet aggregation and stroke. If we think ME might be autoimmune a B cell depleting drug probably makes most sense since there is rather little evidence of cytokine based inflammation. There are other drugs that target B cells and other anti-CD20 drugs but rituximab has proved much the most practical up until recently. There are better anti-CD20 drugs coming through but the advantage of rituximab for ME is that it is out of patent so is likely to be much less costly.
     
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  9. Kati

    Kati Patient in training

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    i really wish we had better understanding of the pathology and immunology of ME so we could get drugs that targets that pathology.

    Right now patients are left to self-experiment or experiment along with their dr of choice, that is if they want to and if they can afford to. N=1 experiments is what is happening now.

    With 5-6 millions of US federal funding for ME research (and much less everywhere else) sadly, we are not going anywhere fast. So much is needed. Case definition, maybe. Biomarkers, definitely.

    Sorry for my rambling. Preaching to the choir.
     
    Last edited: Oct 25, 2014
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  10. deleder2k

    deleder2k Senior Member

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    @Kati a lot of stuff is going on at the moment. I was at Haukeland University Hospital last Friday and I was told that the open phase 2 Rituximab study was around the corner. Olav Mella is working day and night with it. They expect similar results to the blinded study (I think significant effect for 6/9 if I remember correctly).
    Phase 3 is underway, and I will get my infusion (Rtx or Saline) sometime next week.

    Patent has ran out in Europe, and is running out in the States in a few years. Last year the third generation anti-CD20 drug Obinutuzumab (which is more effective in killing B-cells) was approved by the FDA. I'm not sure whether that drug will work better for those who suffer from an autoimmune form of ME or not, but I know the researchers at Haukeland are investigating it.

    Interesting times.
     
    Last edited: Oct 25, 2014
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  11. Kati

    Kati Patient in training

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    @deleder2k great news, looking forward to trials results.
     
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  12. cman89

    cman89 Senior Member

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    I was wondering about the cytokine effect, since many systems of general malaise can be traced to the cytokine overload. If you dont mind me asking, what evidence regarding ME points away from the cytokine effect specefically? I mean if b cells are causing problems, but the cytokine effect is rather discredited, where would the likely problem be? (Immunology is my weakest subset of knowledge in human physiology. I trained as a phsyio guy, so...)
     
  13. Jonathan Edwards

    Jonathan Edwards Senior Member

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    Repeated studies of ME/CFS patients have given very variable and generally unconvincing evidence of ciruclating cytokine abnormalities. Moreover, many cytokines link in to a raised CRP level and this is not usually seen in ME. There are some hints relating to IL-8, TGFbeta and IL-17 but not consistent.

    Autoimmune disease mediated by B cells and antibodies can cause disease through a whole host of pathways other than cytokines - complement or antibody-dependent cytotoxicity or direct intracellular effects of antibody on cells do not necessarily produce any cytokine response. In systemic lupus severe kidney or neurological disease is not usually associated with evidence of cytokine changes. Autoimmunity is not necessarily 'inflammatory' at all. The effect of antibodies on thyroxine levels in Grave's disease is not inflammatory, for instance. It is certainly possible that cytokines are working locally in microenvironments in ME but so far we do not have the evidence. I actually think that it is justified to try cytokine inhibitors, but some have already been tried without much benefit - particularly TNF inhibitors.
     
  14. Kati

    Kati Patient in training

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    i think this cries out the need for biomarkers, better understanding of the disease pathophysiology and the need for separating patients into clearly defined subsets. Until then, yes cytokine research will be muddled because we are comparing oranges with apples. It is terribly difficult to even stop comparing oranges with apples, because at this point in research we are investigating 4 inches round fruits and can't make a distinction between oranges and apples yet (and I am not talking about depressive case, i am talking within ME since we know it's heterogenous)

    In my case, definitely Anti-TNF would be useless because on the 2times i had my cytokines tested (Miami) my TNF levels were below normal. IL-13 if I remember well was 20 times the upper limit of normal range.
     
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  15. justy

    justy Senior Member

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    For me only IL8 was very high - I have no idea what this means...
     
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  16. cman89

    cman89 Senior Member

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    Makes sense now. Thanks.
     
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  17. Sherlock

    Sherlock tart cherry etc. for joints, insomnia

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    It's been a while since I've thought about this but IIRC the onset of benefit in the M&F study occurred long before one would expect any possible auto-antibodies to be cleared from circulation.
     
    Last edited: Oct 29, 2014
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