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Who tried immunosupressive treatment/drugs?

Discussion in 'General Treatment' started by DanME, Aug 9, 2014.

  1. charles shepherd

    charles shepherd Senior Member

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  2. charles shepherd

    charles shepherd Senior Member

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    Regarding the use of prednisolone and other immunosuppresive drugs in ME/CFS

    These results from two very small uncontrolled trials here in the UK were never properly reported in the literature and date back 30 years:

    Prednisolone at 10 to 60 mg/day produced no overall benefit and anecodotal reports from several patients who have been prescribed higher doses of steroids also indicates that while a few have reported some improvement this has not been so for most cases and some people have felt worse, or much worse

    A two month course of prednisolone at 30mg per day, with or without azathioprine (another immunosuppresive) at 150 mg/day, was also tried in 10 cases but no change was reported. In fact, this group were more symptomatic at the end of the course
    The sooner we get to grips with the fact that there various clinical phenotypes and disease pathways under the ME/CFS umbrella the better
    It's rather like placing anyone with any type of joint disease - mechanical, infective, inflammatory - under a chronic joint pain syndrome and saying that they all have the same underlying pathology and will therefore respond to the same approach to treatment
     
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  3. Jonathan Edwards

    Jonathan Edwards Board Member

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    Steroids increase neutrophil counts but making the blood vessels 'forget to be sticky in response to chemokines'. If the blood vessels are not sticky the neutrophils just keep going round and round the circulation instead of going out to patrol the tissues. It is confusing because neutrophil counts normally go up because during infection more are made, rather than (with steroid) less been used up.

    Jonathan Edwards discussion of "What ME might be" is continued here.
     
    Last edited by a moderator: Aug 10, 2014
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  4. deleder2k

    deleder2k Senior Member

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    Anyone else tried? I am especially interested in Methotextrate. With frequent check ups and folic acid, it seems that it is not that dangerous.
    Remember that It was the remission after a round of Methotextrate treatment, for a patient diagnosed with lymphoma and ME, that led Fluge and Mella to try B-cell depletion with Rituximab. Methotextrate got him temporarily "healthy again". Methotextrate is cheap, and is available in a pill form.

    What is there to lose for long term sufferers?

    Edit: just realised i have tried an "immunosuppressive drug", called Kenacort-T 40 mg/ml (Cortisone). Not sure how much it helped me. Felt better for a some days, but it was just a minor effect. Helped my pollen allergy though.
     
    Last edited: Aug 21, 2014
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  5. Jonathan Edwards

    Jonathan Edwards Board Member

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    Methotrexate in low dose works moderately well for certain conditions where there is major cytokine driven inflammation - like rheumatoid and psoriatic arthritis, and also for psoriasis. In low dose it is probably not much use just as an immunosuppressant for autoimmune disease without overt inflammation - which I think ME would fall under. In higher doses used as part of immune suppression it is quite toxic. Even at low dose, errors in prescribing have sometimes led to bone marrow suppression. So the likely benefit is difficult to predict. That being the case I think it might be justified to do a placebo controlled trial. One off usage is hard to justify because of the placebo effect confusing interpretation. A difficulty with a placebo controlled trial is that most people taking methotrexate know they are taking it because it produces at least mild nausea or GI upset.

    You might ask why go on studying rituximab without trying methotrexate since it is much cheaper. I think an important point here is that if rituximab works it tells us something fundamental about the ME disease process that is responding. If methotrexate works it would not tell us much. The other point is that if methotexate was really good for ME then it would have come to light when people with ME hapened to be treated for other reasons and apart from the Norwegian case this does not seem to have happened. That may not mean much but it suggests that methotrexate is not an easy answer.
     
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  6. deleder2k

    deleder2k Senior Member

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    Thank you for the answer. As you point out, methotrexate don't seem to be the answer. Rituximab is more specific, and works better. I thought however that i could help the sickest ME patients before Rituximab treatment is available. Fluge and Mellas patient had lymphoma cancer and was treated with a high-dose of methotextrate. Too bad if low doses won't have the same effect.
    From my understanding, it will be 3 years before the phase 3 study in Norway will be published. Fluge and Mella sent out a statement today saying that the study will launch in late August. 152 participants. They also say that they are overwhelmed by the response, and that study centres are forced to draw from patients which fulfill the Canadian criterias.
     
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  7. Ninan

    Ninan Senior Member

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    Some gossip and uneducated guesses while waiting for Fluge and Mella to publish:

    I heard from someone that they make a difference between patients who got ME after a mono infection and others. Since we know they are looking for factors that might be able to predict the response from rituximab, that difference might have something to do with that.

    They have said that rituximab probably doesn't work through killing off EBV viruses, since the effect would come quicker then. But looking at the PWME:s who got better and seem to stay better, I only know the trigger infection (or at least what seemed to be the trigger infection) in two cases, but it was mono in both cases. Elene, the girl who carried the canoe on TV and Maria G both seem to have a great and lasting effect and they both got ME after a mono infection. Could it be that the ones who stay well are the ones who got ME after an EBV infection? That rituximab in their cases doesn't just stop the autoimmune process but also eliminates the source of the problem, eg EBV? While some others might get better from rituximab but are not cured / have long term effect?

    If this is the case, then it might tell us something about what is causing the autoimmune reaction. If it's viruses, then the rest of us might have viruses who don't hide in the B-cells but in the ganglia (HSV-1), brain etc, which are not as easy to just kill off. (At least not without undesired effects. :p )

    All this assuming that viruses who are hiding and hardly show up on a blood test can cause autoimmunity involving B-cell activation. Hope they publish something soon cause I fear my guesses aren't very educated ones. :oops:
     
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  8. Ninan

    Ninan Senior Member

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    Wasn't the patient who got better from methotrexate the same patient who got better while treating her lymphoma? From what I read they have tried MTX on two patients: Her and a man who had no effect at all. She had effect from 10 mg MTX/week but only for about 25 weeks.
     
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  9. deleder2k

    deleder2k Senior Member

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    Yes, the patient was treated for lymphoma.

    I've also heard so. I wonder why that is. I read however that methotrexate have a larger anti-inflammatory effect than immunosuppressive. From my understanding Cyclophosphamide and Azathioprine does a better job reducing the activity of the immune system. Maybe @DanielBR knows more about this :)
     
    Last edited: Aug 21, 2014
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  10. DanME

    DanME Senior Member

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    From the Fluge and Mella pilot study (2009). The Mtx dose their first patient got during her chemotherapy was a moderate 30mg/m2 iV every third week. Her case started also with a bad case of Mono. She was ill for 7 years.

    "The MIME chemotherapy regimen contains methotrexate (Mtx) in moderate doses (30 mg/m2intravenously every third week). Based on the observed clinical benefit on CFS symptoms in this patient from MIME, the lack of improvement from the three other chemotherapy regimens, and the known (but poorly understood) immunomodulatory effects of low-dose weekly Mtx treatment in e.g. rheumatoid arthritis, we speculated that the observed clinical improvement was related to Mtx. One of the effects of weekly oral Mtx is a moderate B-cell depletion [12]."

    After that she was offered Rituximab and improved after 6 weeks. She got it twice and then Mtx again, which worked for 25 weeks (7,5mg to 12,5mg). After that she got Rituximab again in combination with Mtx.
     
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  11. deleder2k

    deleder2k Senior Member

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    Can anyone share their experience with prednisone? I guess a few have tried that.
     
  12. Ninan

    Ninan Senior Member

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    According to Jonthan Edwards MTX doesn't supress the immune system in the RA dosage. It's too low for that.
     
  13. fibrodude84

    fibrodude84 Senior Member

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    Been on 25mg of methotrexate & 50mg of mercaptopurine for crohns, didn't help fatigue but made it worse.

    Been on biologic meds remicade, humira and cimzia and it doesn't help ME/CFS.
     
  14. Ninan

    Ninan Senior Member

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    Thanks for sharing, @fibrodude84

    Too bad they didn't help!
     
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  15. Sing

    Sing Senior Member

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    @charles shepherd and @DanME
    From time to time on this forum there are threads where those who have benefited from hydrocortisone/cortisol, or not, have been discussed. My understanding is that if the adrenal gland were completely non-functional, a full replacement dose would be between 30-40 mg hydrocortisone or cortisol. Prednisone, however, is 4X stronger, so that would mean a maximum of 10 mg prednisone would be a full replacement dose.

    A number of people with ME seem to have a lack of cortisol either through a lack of timely response to need by the HPA or perhaps through some form of resistance to it--I don't know. However, these people can benefit from low-dose cortisol supplementation.

    I am one of them, having been using 5 mg twice a day for many years. It has helped my condition a great deal, without any adverse side efffects. It also improves my immunity. The sore throat and flu symptoms I used to get with any over exertion (meaning approximating a normal day) were banished. Some others on this forum have had the same benefit.

    This kind of supplementation of cortisol may not be what this thread is driving at--the question of whether or not very high doses well beyond a physiological replacement dose could be of benefit. Instead it is along the lines of taking additional thyroid medicine for a low-performing thyroid gland. Except that in the case of this group of MEs, the health of the adrenal gland is not the problem but rather the lack of adequate signalling from the HPA, most likely.

    My impression is that this low-dose supplementation has not been adequately tested in proper studies. Either excessive doses were tried, or the patient group may have been poorly chosen via the conflation of ME/CFS with Depression--and it has been found that those with Depression have excess cortisol rather than a lack of it--so I don't think this avenue for treatment, not cure, for at least some MEs has been adequately looked into yet.
    Safe Uses of Cortisol by Dr. William Mackenzie Jefferies, M.D., 1996, is a resource of information for the history of the use of cortisol and its value in low doses for a number of conditions, including ours.
     
    Last edited: Jan 21, 2015
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  16. RYO

    RYO Senior Member

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    I could be mistaken but I read somewhere that CFS / ME patients more prone to placebo effect. I have personally tried prednisone 40 mg for 4 days during one of my exacerbations. It did not help. In fact I have been unable to return to my "baseline" state. Unclear whether this was just a part of overall deterioration from "overexertion" or from negative effects of prednisone.

    Not sure which subtype of ME I would fall under but my disease started after severe viral infection in May of 2012. The most likely culprit was an Enterovirus after exhaustive medical evaluation.

    I am hoping genetic testing will shed some more light on our disease. Perhaps it will raise more questions than answers.

    Does anyone have any updates from Chronic Fatigue Initiative or Stanford re: update on disease markers or disease pathophysiology. Has anyone thought of using existing blood samples on Stanford subset of ME patients for genetic analysis.
     
  17. Sing

    Sing Senior Member

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    Responding just to the part of your message about prednisone. I am sorry you did not return to baseline after that exacerbation and treatment! That amount of prednisone would have been 4X a physiological dose, so not what I was writing about in terms of low-dose supplementation at all. Regarding your situation though, I know that extra large doses of cortisol are given to people in the hospital who are in severe, life-threatening straits and often this major hormone will help pull them out of it, but when the immediate crisis passes, they will be quickly tapered off, as that amount of prednisone becomes harmful quickly. Very high doses like that are usually just for crisis situations. Maybe that was your situation and afterwards, as you wrote, you either had been harmed by the prednisone or just didn't recover the level you were on before.
     
    Last edited: Jan 21, 2015
  18. melamine

    melamine Senior Member

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    I was on a trial of predinisone 10mg/day for one week. I might have stopped it short a day because symptoms that were beginning to flare shortly before starting were unaffected and continued worsening. I have late onset autoimmune manifestations affecting my nervous system primarily, and sicca syndrome, but no standard issue categorical disease.

    If it makes any difference whether prednisone should have helped: my original illness began with EBV, shifting from stable to steady decline immediately following some outpatient surgery 18 years ago. This was augmented by multiple potential sources of aggravation and a series of evolving new symptoms over the next 10 years.

    A year or so before this trial, at a university clinic where I was seen for about 7 years, I asked the attending rheumatologist if there was nothing they could give me to stop my symptoms from continuing to flare and progress. He wanted to try me on methotrexate but as was his habit, expressed it as a distant pronouncement directed towards the resident rather than speaking directly to me, the patient. For that reason and others, I declined.

    I was unaware of any research regarding mtx and CFS and doubt he was either, or even considered CFS a legitimate condition. In addition, he was continuing to misdiagnose me IMO because he had never taken a proper history to begin with and appeared disinclined to make corrections. For those reasons mtx didn't make safe sense to me from what I understood of it, and because of my labs that were showing consistent evidence of a certain amount of immune deficiency in the context of a fairly recent history of unusual and misdiagnosed infections (but in absence of the usual flus and colds). Maybe I should take another look at methotrexate.
     
  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    An example of a dose of HC used in a hospital setting for severe asthma or allergic reaction is 200mg of hc given iv, so equal to about 40mg prednisone. Thats big doses compared to the 20 to 30mg of HC given for adrenal dysfunction in cfs me. I just mention this so everyone is on the same page.

    There are some who have found only 5 to 10mg of hc in the morning helpful.

    We have to remember that in cfsme that adrenal dysfunction is one of many other possible dysfunctions going on at the same time. Also low cortisol can be just as harmful to your immune system as high cortisol.
     
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  20. Sing

    Sing Senior Member

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    @heapsreal You put it all very succinctly. Having the right amount of cortisol available is just as important as having the right amount of thyroid, or insulin, etc. Then too, the extra high doses used briefly for a hospital emergency are life saving. But long term extra high doses, though they can squash the inflammation and pain in some conditions like RA or Lupus also cause serious damage over time, and so, I believe, aren't normally used now.

    I wish there were studies with "well characterized" ME/CFS patients--who have low circulating cortisol--on low dose cortisol, to demonstrate its value, because getting the right amount on board makes a big difference in quality of life when you don't have enough of this HC.
     
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