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Methotrexate

Discussion in 'Rituximab: News and Research' started by Freddy, Apr 3, 2015.

  1. Freddy

    Freddy

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    Hi,

    as perhaphs many of us I'm searching for treatment and I have been fascinated by the rituximab studies.
    I've been mostly bedbound the last year and consequently at least somehow desperate.
    In Germany it seems actually not possible to receive rituximab, even in case I sign documents that it
    will be offlabel and I accept all risks...

    But my doctors would give methodrexate a trial. So my questions:
    Does anybody has experience with it? Both good and bad experiences are welcome!

    @Jonathan Edwards : You think it is a sensible trail? You once wrote somewhere here that it has no clear cut mode and sience cannot draw conclusions if it works. But in the absence of rituximab, you think it is worth a trial?

    @deleder2k : you wrote that the bergen researches came to rtx through the experience from a chemo comb
    with methodrexate beeing part of. Was also rituximab part of this combo? In other words: can the
    improvement of cfs symptoms of the combo be tracked down most likely to methodrexate?
    http://www.biomedcentral.com/1471-2377/9/28
    Here they reasoned in that direction.

    Maybe I missed some discussions here. Are there topics one can find only as logged in member?
    Any hint welcome!
     
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  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    This is really hard to know what to say on. If your doctor thinks a trial of methotrexate is worthwhile I would respect that. The doubt about mode of action does not matter for you - since you are only interested in your own improvement, not a trial. Methotrexate can cause nausea and headache but many people tolerate it well. The more serious side effects of bone marrow suppression are not a problem with careful management. Also benefit from methotrexate tends to become apparent within 3 months in other conditions, which is quicker than rituximab. I think @charles shepherd is aware of old studies using drugs of this sort, which may not be relevant or conclusive, but at least there seems to be relatively little reason not to give it a trial. If you get no benefit by 4 months I would not think it worth persisting. (But you are unlikely to notice change in less than a month.)
     
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  3. minkeygirl

    minkeygirl But I Look So Good.

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    Left Coast
    @Ninan was taking methotrexate. Search for her.
     
  4. deleder2k

    deleder2k Senior Member

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    @Freddy, no she did not get RTX. She got something called MIME (methotrexate, ifosfamide, methyl-GAG and etoposide).

    This is from Haukeland's latest patent filing.

    From their first study:
    I don't know how much 30 mg/m2 IV every third week translates to in per os.
     
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  5. Ninan

    Ninan Senior Member

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    @minkeygirl I never tried MTX. Got my B12 working again instead and I don't want to mess up the folate effect.
     
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  6. minkeygirl

    minkeygirl But I Look So Good.

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    I just quit methylation Bad reaction to B12. I still would like to try it but an immunologist said he would give me SCIG so want to see what happens with that, if he'll ever get off his ass and RX it for me.
     
  7. deleder2k

    deleder2k Senior Member

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    SCIG is an interesting choice. If you benefit from it I think you'll notice it in 6-12 weeks.

    Professor @Jonathan Edwards, you have previously mentioning that a low dose of (5-10 mg) of MTX wouldn't be enough to have an immunesupressive effect, just a anti-inflammatory. Is that correct? If one want to try MTX against ME, is a large dose needed? I have no understanding of this, but I thought we we're looking to suppress the immune system. The patient mentioned earlier in this thread received 30 mg/m2 IV as a part of MIME. Is that a high dose - and could it lead to serious side-effects?
     
  8. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    I think probably terms like immunosuppressive and anti-inflammatory are too general to be helpful here. Rituximab lowers autoantibody levels. In RA MTX seems to work not through lowering autoantibody levels since the time course is wrong. Moreover, it works just as well if not better in arthritis where there are no autoantibodies (psoriatic). MTX seems to have an effect on lymphocyte mediated processes in chronic synovitis. Although chronic synovitis is theoretically chronic inflammation it does not play by the same rules because synovium has a strange propensity to become colonised by lymphoid tissue - effectively turning into a lymph node.

    So it is all rather complicated and I am not sure I can tease out any further predictions with much confidence in ME!

    The RA dose of MTX is around 12.5-25mg per week - it is given as a weekly oral dose. Higher doses of methotrexate are used as a cytotoxic agent in cancer - maybe 100mg at a time. This is likely to produce a range of significant side effects both symptomatic (nausea) and haematological. Exactly what dose would be appropriate for ME is hard to guess.
     
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  9. deleder2k

    deleder2k Senior Member

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    Thank you.

    I understand this is pure speculation but; Do you think adverse effects would be a problem in RA/ME if patients we're given 25mg weekly? Is it likely to cause serious side effects? Or are they likely to be OK if they are subject to extensive follow-up?

    @Freddy, please keep us updated.
    I am unsure whether my rheumatologist would agree trying this though; however, it is interesting to discuss. I have joint pain, and joint cracking that correlates with the rest of my ME symptoms, but I do not have swelling or redness. The pain is so awful that I have to use oxycodone at times. I wonder if someone is able to receive MTX just because they experience severe chronic joint pain and cracking.
     
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  10. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Most RA patients tolerate 25mg weekly reasonably well but a significant minority get problems like nausea. These are said to be reduced by taking folate. Routine blood tests are needed but haematological problems at this dose are rare.

    MTX is useful for a number of inflammatory joint problems. It is unlikely to be helpful if there is no swelling (redness is not a common feature of chronic synovitis). Cracking of joints is not a sign of inflammation, but rather of a mechanical vacuum effect that can occur normally. Inflamed joints cannot crack because they are at increased internal pressure.
     
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  11. Ninan

    Ninan Senior Member

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    My doctor has a lot of PWME:s and some of them take MTX for psoriasis, RA etc. He has not heard that it should effect their ME/CFS symptoms. A lot of people take MTX and I think that if it was effective against ME in those doses we would know about it. I have searched the net and found maybe four people who benefitted from MTX so it seems it does happen but it's not very common. Could be dose related too, of course.

    About cyclophosphamid, the drug the Norwegian doctors are now trying: It seems that it is available as pills too and it's not very expensive. Is it likely that a ME patient could have effect from the pills? Or is it like RTX and MTX: It has to be taken in larger doses to have the immunosuppressive effect? Would you make an educated guess there, @Jonathan Edwards ?
     
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  12. Joolz

    Joolz

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    Unless your doctor IS prof Scheibenbogen, I would talk to her. I think she has tried it on some of her CFS patients.

    The infusions are cheap, too. But cyclo is definitely a "don't try this at home" drug. !!!
     
  13. Jonathan Edwards

    Jonathan Edwards "Gibberish"

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    Cyclophosphamide by mouth is used for very few conditions because when it was first used about fifty years ago almost half the people taking it developed bladder cancer. For autoimmune disease we stopped using it in the 1980s. Pulsed higher dose IV cyclophosphamide was much more effective and the bladder problem can be blocked with an IV inhibitor. One thing I would worn everybody off is eating cyclophosphamide! As far as I know it is only used as a continuous oral treatment for malignancies like myeloma where there is fairly little chance of survival for ten years anyway.
     
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  14. deleder2k

    deleder2k Senior Member

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    You may be right, but think of all ME patients who have been treated with cyclophosphamide for breast cancer, lymphomas, leukemias etc. I have heard about numerous patients getting better during/after chemo, but none of the hospitals have done anything about it. Doctors can't continue chemo based on the patients subjective experience of a disease many thought/think doesn't exist. One would need to do a study, and that didn't happen before two fine doctors in Norway decided to do so.
     
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  15. Ninan

    Ninan Senior Member

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    Yes, but this is an ME doctor, he is not involved in the MTX, he is just trying to treat their ME. He told me the patients don't notice any effect on ME from MTX, so I guess he must have asked. Anyway, I think we'd know if it was so. MTX isn't that uncommon and many PWME:s have other autoimmune conditions so MTX treatment for PWME:s should be quite common. I'm still thinking of trying though.

    Thanks for the warning @Jonathan Edwards. Playing doctor without experience or education can be a bit risky.
     
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  16. deleder2k

    deleder2k Senior Member

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    It may depend on the dose though. Do you know what dosage he uses?
     
  17. Ninan

    Ninan Senior Member

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    Who? As I said, he doesn't prescribe MTX. His patients are on MTX for RA, psoriasis etc.
     
  18. Freddy

    Freddy

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    Thanks @Jonathan Edwards , @deleder2k , @Ninan and all others for your answers.
    Sry for beeing absent to the discussion for quite some time - had really bad weeks...

    Summarizing what you said, improvements with MTX in CFS/ME should be rather unlikely. Since there are many ME patients with coexisting autoimmune disease receiving MTX, any systematic improvement should be known.
    Basically, my doctor just said that he will not be able to give me RTX, but he may be willing to prescribe MTX.
    Based on your answers and my tendency to catch any cold and infectious disease in my environment
    i'm now very sceptical...
     
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  19. deleder2k

    deleder2k Senior Member

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    I am not a doctor, but what is the worst case scenario? If you are bedridden or unable to get out of the house I would seriously consider it.

    If one believe in the hypothesis of the Norwegian oncologists I think the following drugs make sense:

    - Rituximab
    - Cyclophosphamide
    - Nitroglycerin (problem is tolerance)

    These are worth looking at:

    - Gammaglobulin
    - Mycophenolate mofetil (not sure if anyone has tried this)
    - MTX

    Have you tried gammaglobulin? I think I would try that first. You could also have a look at nitroglycerin. You should read Øystein Fluge and Olav Mella's patent application here. They basically say that those who responded experienced a decrease in all ME related symptoms.
    The interesting thing about nitro is that it works rather quickly. Fluge and Mella state in their application that 4/6 patients benefitted within 2 weeks with the use of isosorbide mononitrate. I am not aware of major adverse effects if used in low doses - but I have no medical knowledge, so I wouldn't know :) My doctor said he would prescribe it. He said that the most common side effects were dizziness and low BP. I have a normal blood pressure (120/80). He wouldn't prescribe it to a patient with low BP or someone with a pre existing cardiovascular disease.
     
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  20. Freddy

    Freddy

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    Hi @deleder2k , you are really very positive and constructive!

    I wasn't aware about the nitroglycerin story. Is this the combination of:
    " L-Arginine 5 g twice daily combined with L-Citrulline 200 mg twice daily"?

    Gammaglobulin was once considered (I had low IGG subclass 3). Need to contact the Berlin researchers again...
     

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