Home care is the theme for Severe ME Day on August 8th
Why should home care be the theme on Understanding and Remembrance Day for Severe ME on August 8? Helen Brownlie of the 25% ME Group has written an explanation for Phoenix Rising ...
Discuss the article on the Forums.

Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July

Discussion in 'General ME/CFS News' started by Sasha, Jul 30, 2013.

  1. Kati

    Kati Patient in training

    Messages:
    2,994
    Likes:
    4,865
    Good luck with methotrexate, @Ninan, let us know how it goes.

    Do you know if you will be on a dosage similar to RA?
     
    vli and NK17 like this.
  2. NK17

    NK17 Senior Member

    Messages:
    590
    Likes:
    1,487
    Cross my fingers for you @Ninan and wish you a long stretch remission with the methotrexate treatment.

    Please report on PR whenever you can.
     
    Ninan likes this.
  3. Ninan

    Ninan Senior Member

    Messages:
    301
    Likes:
    233
    @Kati Yes, I'll take the standard RA dose, starting low.

    @NK17 Thanks. I'll keep you posted.
     
    vli likes this.
  4. catly

    catly Senior Member

    Messages:
    276
    Likes:
    677
    outside of NYC
    @Ninan Good luck and please keep us posted.

    I've had 2 rheumatologists suggest that I start placquenil or possibly methotrexate treatment because of my +ANA, high TPO (hashimotos thyroiditis), low+ CCP (antibodies for RA) and sicca syndrome. All this coincided with onset of ME.

    I never started the treatment because I started on the path of antivirals and LDN as recommended by my ME/CFS specialist.

    I would do it in a heartbeat if I thought it might help.
     
    vli and Ninan like this.
  5. Ninan

    Ninan Senior Member

    Messages:
    301
    Likes:
    233
    catly likes this.
  6. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    2,548
    Likes:
    10,381
    Dear Ninan,
    I do not know of tecfidera I am afraid. It is hard to say what other drugs to recommend even if one guesses thatthere may be an autoimmune basis. Methotrexate works in RA at a dose that is too low really to be very immunosuppressive - nobody knows how it works I think. Azathioprine has often been used in the past for immune disorders but I gave up using it because of worries about skin cancers. The reason why, like Drs Fluge and Mella, I am interested in rituximab is that we know exactly what it does and so if it works it will tell us where else to look. There are other anti-B cell agents like belimumab, but quite when they would be helpful is still uncertain.

    So I am not sure I am much help on this one. At least methotrexate seems worth a try since Dr Fluge noted an improvement in one of his cases.
     
    vli, Kati, rosie26 and 2 others like this.
  7. Kate_UK

    Kate_UK Senior Member

    Messages:
    242
    Likes:
    261
    Fundraising for the UK trial is now at £347,046 of £350,000. Less than £3000 until target.
     
    NK17, catly, ukxmrv and 4 others like this.
  8. Min

    Min Guest

    Messages:
    1,386
    Likes:
    1,900
    UK

    Yabadabadoo!
     
    Kati likes this.
  9. Ninan

    Ninan Senior Member

    Messages:
    301
    Likes:
    233
    I wonder if the RA dose for MTX isn't too small. I've found four or five cases of PWME:s getting better from it and all but one or two of them received higher doses, while treating lymphoma or for other reasons. Olof Zachrisson at the Gottfries clinic says he has had many patients on MTX for psoriasis and RA and he has never heard of any of them having any effect on their ME symptoms. If it was common I think we'd know about it. It's not a rare medication.

    Does anyone know how sure the researchers are that it’s B-cell depleting effect from rituximab that is causing the effect? Could it be something else? (I know there’s the EBV theory but in that case the effect would also come from depleting B-cells.) It seems all medications aimed directly at depleting B-cells are very expensive and complicated to administer.

    Azathioprine seems pretty nasty but interesting, @Jonathan Edwards. Maybe if it was used for ME one wouldn’t have to give it during such a long time?

    A friend of mine who’s a neurologist mentioned Purinethol. From what I understand they both lower the number of B-cells and are given to patients who’s had a transplantation and to patients with autoimmune disorder under the course of many years, hence causing severe side effects. (I read somewhere that about 50-95 percent of transplantation patients had developed cancer 20 years after the transplantation and that there was a strong suspicion that this was because of the immunosuppressive medications. That’s a huge number.)

    But if one would try to use Azathioprine for ME, maybe the course of treatment could be shorter? Instead of giving it as a long-term maintenance therapy you could try to imitate the rituximab-therapy given at Haukeland. Start depleting B-cells and when they’re down to a certain number simply stop the treatment and see if there is an effect after 2-8 months. If these medications do about the same thing as rituximab (though I guess they do other things too) and if B-cell depletion is the reason rituximab is working, then maybe you could expect about the same result. The course would have to be repeated if the patient got worse again but the risk of getting serious side effects like cancer would probably be much smaller if the treatment wasn’t long term, right? (From what I've read the risk of getting skin cancer is so much bigger because patients get extremely sensitive to UV light while on the medication, not because of some long lasting effects. But they don't seem to be a 100 per cent sure.)

    I guess rituximab is the better alternative since you know exactly what it does. But when given in shorter courses maybe the risks with these other medicines would be about the same as with rituximab? And the costs very much smaller, which is important to us since doctors are much more willing to use a medication off label if it doesn’t cost a fortune. Even if it’s not as effective and has more potential side effects than the expensive one.
     
    Last edited: Aug 5, 2014
    catly and MeSci like this.
  10. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    2,548
    Likes:
    10,381
    Rituximab definitely works by depleting B cells. It has no consistent effect on anything else as far as we know and one would not expect it to, which makes it so useful as a help to understanding mechanism. Azathioprine does not work by depleting B cells, which change rather little on azathioprine, so I do not see any prospect of it being useful in short bursts. It also makes quite a lot of people nauseous.
     
    vli, catly, NK17 and 2 others like this.
  11. Ninan

    Ninan Senior Member

    Messages:
    301
    Likes:
    233
    Bummer. Thought I had solved it. :cool: I guess if there was a cheap alternative doing about the same thing, rituximab wouldn't exist.

    Anyway I'm starting MTX on Monday, 2,5 mg and raising 2,5 every week if I tolerate it ok. I think my doctor wants to go as high as 7,5 mg/week. The woman in the Fluge/Mella study had an effect from 10 mg, but she started it while having effect from rituximab so I guess our starting points are quite different. For her it lasted for 25 weeks. I'm hoping for a miracle but expecting nausea. If anyone is interested I’ll be updating here.
     
    vli, MeSci, catly and 1 other person like this.
  12. NK17

    NK17 Senior Member

    Messages:
    590
    Likes:
    1,487
    Good luck @Ninan. I'll follow your treatment's report ;).
     
    Ninan and MeSci like this.
  13. MeSci

    MeSci ME/CFS since 1995; activity level 6

    Messages:
    5,985
    Likes:
    7,998
    Cornwall, UK
    Don't give up trying - you never know!
     
    Ninan likes this.
  14. aimossy

    aimossy Senior Member

    Messages:
    3,862
    Likes:
    5,887
    @Jonathan Edwards I'm wondering what you think of this. Its from the latest article on here about the invest in ME conference.
    I was wondering about this ADMA, I remembered some of the discussions about the theory of NO and endothethial function, but to be honest my brain looses information. I googled this ADMA and of course one thing does not necessarily relate to another. I'm really just wondering what you make of it, I know its all theoretical but I found this interesting.
     
    rosie26 likes this.
  15. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    3,064
    Likes:
    3,772
    Australia
    The above statement is from Mark Berry's article, rather than the IIME website. The finding is interesting, but still unknown what it really means. My question would be, did they control for B vitamin supplementation as that could be a mediator of those findings.

    There was however a study that found elevated levels of asymmetric dimethylarginine levels in Fibromyaligia, which was also correlated with TNF-α levels.

    http://www.sciencedirect.com/science/article/pii/S0009912011000397

    That article came up in Google scholar since I was searching for asymmetric dimethylarginine and fatigue.

    Edit additionally: Increased asymmetric dimethylarginine levels have also been found in depression (and decreased Nitric Oxide too).

    Oh and I am very glad to hear the Rituximab study is more or less completely funded now!
     
    Last edited: Aug 10, 2014
    aimossy likes this.
  16. Jonathan Edwards

    Jonathan Edwards Board Member

    Messages:
    2,548
    Likes:
    10,381
    Mady Hornig is doing some very interesting work at present. I have to say I did not pick up on this molecule, which Mark noted her report on. It is not something I know enough about to comment on really.
     
    aimossy likes this.
  17. Mark

    Mark Acting CEO

    Messages:
    4,734
    Likes:
    2,474
    Sofa, UK
    I hope I got it right. As I remember it, this was the only thing in her talk that sounded like new info, so I took special pains to take accurate notes, and I'm pretty sure the words "hot off the press" were Mady's own words. I haven't even looked up what ADMA is, but if there's an endothelial connection then that sounds potentially exciting to me.
     
    RL_sparky and aimossy like this.
  18. aimossy

    aimossy Senior Member

    Messages:
    3,862
    Likes:
    5,887
    Thanks @Jonathan Edwards ,
    When I read about it in Mark's article (thanks Mark :) ) I googled ADMA and wondered if this could have some affect on NO and endothelial function. I thought 'far out', has Mady Hornig possibly found something that could support the theory that Fluge or Mella have. ( I'm sorry I couldn't remember which doctor of the two had the theory).
    It's pretty neat when you see something that might translate across peoples research or theories. I know its theoretical, but still - I thought it was a very neat idea and was very excited for a whole day! I am just hoping to hear more about it.
     
    rosie26 likes this.
  19. Marco

    Marco Old blackguard

    Messages:
    1,834
    Likes:
    1,726
    Near Cognac, France
    Re ADMA (which I'd never heard of previously) elevated ADMA appears to be associated with various pathologies and the only example I could find where AMDA is low is in premature infants with necrotizing enterocolitis :

    Low plasma concentrations of arginine and asymmetric dimethylarginine in
    premature infants with necrotizing enterocolitis


    Reduced arginine (not reported by Hornig?) and ADMA may be a risk factor or result from gastrointestinal infection or impaired gut microcirculation :

    http://www.ncbi.nlm.nih.gov/pubmed/17381965

    I wonder if the ADMA finding partly explains Hornig and Lipkin's interest in the gut microbiome?
     
    catly, Sidereal and aimossy like this.
  20. aimossy

    aimossy Senior Member

    Messages:
    3,862
    Likes:
    5,887
    @Marco Thanks for the above, that is really interesting. I did find some papers about some conditions with low ADMA and have no clue where I found those in now. I came away after flicking through these feeling that quite a few illnesses may have low ADMA, so I thought well it may not be unique to ME but still abnormal in some illnesses. I wonder if its one of those things where if your body is under strain it shows up ( yes rudimentary thinking, I'm not proclaiming some scientific brain).
     
    Last edited: Aug 11, 2014

See more popular forum discussions.

Share This Page