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Enbrel, next after Rituximab

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by redo, Sep 25, 2012.

  1. redo

    redo Senior Member

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    As we know, a significant percentage; one third of the patients, in Mella/Fluge's study didn't respond to RTX. And what the science team is doing next, is a study on Enbrel.

    Mella/Fluge writes the following: There are no published scientific published study that evaluated the use of Enbrel in CFS / ME. However, there is a contemporaneously where six CFS / ME patients had been treated with etanercept with good clinical effect, but these results have not been published later (Lamprecht K. American Association of Chronic Fatigue Syndrome, Seattle 2001). In addition, individual patient unpublished stories available (link).

    'Kristin' says the following about Enbrel: "I was in a “pre-study” with Enbrel back in 2000. I have CFS-moderate. For the first weeks-nothing. Week 5-8 I felt wonderful. Not completely normal, but SO much better. I cried when I had to stop at 8 weeks and found out the cost of Enbrel. What I would not give to see Enbrel further studied and approved for CFS treatment. (link)"

    I'd like to open a thread, brainstorming for reasons it might be effective/not be effective, and arguments one could use for getting on it.
    Sasha, snowathlete and mezombie like this.
  2. liquid sky

    liquid sky Senior Member

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    Another autoimmune drug. It is typical in autoimmune disease for different patients to react favorably to each medication. Some do not react favorably to anything. One rheumy told me about 40-50% do not get relief from available medications for autoimmune symptoms.
  3. ukxmrv

    ukxmrv Senior Member

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    I've not tried enbrel but humira instead. My tnf-a was high before.

    Both drugs are used by reproductive immunologists in experimental miscarriage treatments.
    There is a lot of info available from these groups on enbrel and cytokine levels.

    The humira reduced my tnf-a levels. Sorry I can't get to my med records to show what other levels were changed. We did some th1/th2 tests as a baseline.

    The main change in my m.e. symptoms was a noticable decrease in sore throats, glands etc. This being a major part of my symptoms then.

    Dr Kerr in the UK wanted to trial these drugs but usual story of funding cut and then sadly he lost his lab.
    Sasha likes this.
  4. redo

    redo Senior Member

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    liquid sky. A friend of mine (with a different auto immune disease) whom have been on several immune modulators and failed, and for him what really have worked has been Enbrel. It took about a month, and for him it was like an on/off switch. From what I've read, it's common with many autoimmune diseases to try a new immune modulator if one doesn't work. And that it differs much from patient to patient what works against their disease. For example, in order for RA patients to get RTX, they have to have tried other immune modulators first. So, I am rather optimistic about the chances that if one doesn't work, others might.
    Sasha and dsdmom like this.
  5. SpecialK82

    SpecialK82 Senior Member

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    Very interested in their study, thanks for posting redo!
  6. liquid sky

    liquid sky Senior Member

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    Yes, when an immune modulator works, it is sometimes like throwing a switch. I have tried many of them, but only one worked a little. I asked a rheumy why they don't do tests of the immune system first to see what is wrong in each patient. She said the tests they do in studies are cost prohibitive to be done with each patient before treatment.

    In other words, the insurance will not pay for the tests. It is cheaper for them to put you through one med after another than to do the tests and put you on the drug most likely to help you (and the drugs are very expensive). Never mind that these drugs have very serious side effects and it would be best not to use ones that have no chance of helping you. That is not the goal of insurance, but rather spending the least amount of money while fulfilling their contract.

    The patient population that has been gathered under the umbrella of CFS and ME are so varied that they will probably be like RA patients who react differently to these drugs. I would love to see a study of ME patients with polyclonal B cell activation performed with a drug trial of rituximab.

    We are going to have to split up the patient population under very specific markers and try drug trials before we are going to get anywhere with this disease/diseases.
    Sasha and redrachel76 like this.
  7. natasa778

    natasa778 Senior Member

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    There is a thread on this in rituximab folder - I posted there on the initial trial of Enbrel for cognitive dysfunction/Alzheimers, which had some amazing initial results.
  8. redo

    redo Senior Member

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    Mella/Fluge also write (my bolds):

    We have had contact with a 35-year-old woman who has had severe CFS / ME with a typical clinical picture of 16-years of age who for years was significantly isolated and disabled by the condition.

    She had a moderate rheumatoid arthritis 27-year-old, and started as a 31-year-old with Enbrel administered subcutaneously every week and have used the drug last 5 years. She explains how Enbrel during the 2-3 weeks resulted in a significant clinical effect on all symptoms related to her CFS / ME. She describes clearly how the ME disease is still present, and that she must be aware of in terms of load factor, but that she still has a significant change of quality of life. Such a description is consistent with our idea that CFS / ME can be a form of autoimmune disease.

    Enbrel may have more side effects than Rituximab, and is somewhat more associated with risk of infections and paradoxes disorders of the immune system. Drugs are still in widespread use in the treatment of rheumatoid arthritis with good results and acceptable safety profile. Toxicity profile of Enbrel in CFS / ME is unknown.

    We want to try treatment with Enbrel for up to 15 patients with moderate and severe CFS / ME, including patients who have not had a response after treatment with Rituximab-maintenance (5 infusion and 12 month follow-up), with weekly subcutaneous injections for up to one year.
    http://www.sfc-em-investigacion.com/viewtopic.php?t=1915&p=9792

    natasa778. I'm adding a link for reference here with regards to your post. I think perispinal injection sounds really interesting in general, because it's used with (preliminary) success against various syndromes involving neurological symptoms. If I could choose, I'd actually prefer to have injections done like that. Here's a video with a patient getting it that way (they have cut out the injecting part, but the rest is there). It seems to me there must be some kind of benefit doing it perispinal, since sub cutaneous is so much easier, and if equal SC should be preferred... Anyone who could weigh in about this?
    Sasha, natasa778 and heapsreal like this.
  9. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

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    That would depend on where you think the main benefit would occur. If in the spine and possibly brain (as in Alzheimer's), then yes. If in the body at large (as in RA), then you'd be in effect keeping the drug away from where it's most needed. The perispinal use in sciatica is apparently when it's disc related, i.e. discogenic.

    It's probably more risky to go perispinal. Isn't there a theory of M.E. about a virus in the dorsal root ganglia? Tobinick 2006: "... perispinal administration of etanercept in small pilot studies suggest that perispinal administration of p38 inhibitors may also allow these compounds to reach the spinal cord and dorsal root ganglia..."
    http://www.tnfmedicine.com/tnf/cerebrospinal_venous_system/

    So it could conceivably allow activation of a virus that had been kept contained. OTOH, if there's only inflammation there to be quenched, then perispinal would seem to be a very good idea.

    Perispinal route needs doctor training, e.g.: "Perispinal Enbrel Hands-On-Instructional Course" (also they mention systemic candida as a problem: http://reversealzheimersnow.com/contraindications-to-enbrel.html so I'd avoid sugar while taking etanercept)

    In going perispinal, if the 1st dose doesn't produce any effect, maybe that's a sign to not ever repeat it - either stop etanercept completely or else try it as subQ). Whereas in going subQ you'd likely administer for some period before expecting any effect.

    The term perispinal injection seems specific to Tobinick style uses. It seems to be injected inside the vertebra, but not into the cerebrospinal fluid itself. I don't know how it differs from epidural.
    Sasha and redo like this.
  10. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

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    Why is etanercept not used to treat MS? Why does etanercept sometimes cause MS?
  11. liquid sky

    liquid sky Senior Member

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    Interesting, because some drugs that are used for RA are contradicted for MS. As you say, they can actually cause MS by causing demyelination of the nerves in the brain and spinal cord.
    Sherlock likes this.
  12. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

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  13. Sherlock

    Sherlock bicarb for exercise recovery and taming candida

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    speaking of dorsal root ganglia and spinal administration of etanercept:

    "It has also been reported that IL-1, IL-6, and TNF-a are activated in dorsal root ganglia and Schwann cells in the spinal nerve roots following lumbar spinal stenosis, and that their expression is closely related to pain, motor nerve
    dysfunction and degeneration."

    "Epidural administration of spinal nerves with the tumor necrosis factor-alpha
    inhibitor, etanercept, compared with dexamethasone for treatment of sciatica
    in patients with lumbar spinal stenosis: a prospective randomized study"
    http://drmelrichardson.com/Publications/epiduraletanerceptspinalstenosis.pdf

    So, if M.E. pain is radicular pain (radiating... felt in areas such as arms or legs but it's really caused by inflammation at the nerve root far away), then administration of the etanercept into the spinal compartment is ideal. That way tends to more insure that adequate drug hits the target.- and avoids the risk of administering etanercept to the entire body. The overall drug dosage is probably less, too.

    But what about other CFS symptoms besides pain? Possibly IV is best for those.

    ------------------

    Also, I did just now watch the video of the guy getting etanercept from Tobinick for radicular sciatica and having fast response, literally in minutes. www.youtube.com/watch?v=BM7coDtj4Mc Note that the benefit lasted up to ~4 years! from one injection.

    It is dramatic, and argues in favor of the MOA of breaking a self-perpetuating cycle of pain/inflammation. The same can be true in the fast responses to RTX in CFS. So, for anybody not getting RTX or Enbrel, is it possible to break that cycle using something else? Quercetin, trans-resveratrol, EGCG? Ice baths? Something?

    The whole auto-antibody thing is another story, and is only speculation anyway. Not very compelling, IMHO, except for the late onset of the effects in the M&F study. Note that the original serendipitous Pts (4?) had fast onset of effects, so did Jacque.
    redo likes this.
  14. redo

    redo Senior Member

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    Thanks to Sherlock for some great input.

    Although on a case basis, improvement lasting four years is amazing. I agree that it indicates breaking a 'viscous inflammation cycle'. I friend of mine has just finished her doctoral thesis in immunology, and I've been told time and time again about the potential in breaking such cycles. In the RTX patients not needing continuous doses, it might very well be that which have happened. Lucky them.

    I'd like to read more about that, please do share a link if you've got one handy.

    About subcutaneous/interspinal, I found this excerpt interesting: Because of the inability of large molecules such as etanercept to cross the blood brain barrier following conventional systemic administration, it is likely that the more direct drug delivery system pioneered by Tobinick also contributed to the effectiveness of the treatment. If so, this system could be useful in drug delivery to the brain in other neural disorders, as well as in animal research studies, many of which currently employ delivery strategies that inflict damage to neural cells and thus engender neuroinflammatory responses.
  15. liquid sky

    liquid sky Senior Member

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    http://arthritis.about.com/od/arthritismedications/f/contraindicated.htm

    TNF Blockers


    TNF blockers Enbrel (etanercept), Remicade (infliximab) and Humira (adalimumab) are contraindicated in patients at high risk for infection or recurring severe infection; patients with prior exposure to TB (tuberculosis) who have not been treated; patients with lymphoma and patients withdemyelinating conditions such as MS (multiple sclerosis).
    Another drug not mentioned here is Actemra which is given IV and depletes the cytokine IL-6. It is also contradicted in MS or demyelinating diseases. There are probably others I'm not aware of.
  16. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    On the subject of TNF blockers etc the antidperessant wellbutrin/bupropion has anti-inflammatory effects by lowering TNF levels. http://www.ncbi.nlm.nih.gov/pubmed/16644475 this study shows it lowers this inflammatory cytokine in patients with crohns.
    snowathlete and redo like this.
  17. Ruthie24

    Ruthie24 Senior Member

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    @heaps- I've wondered if this is why my c reactive proteins and ANA tests are always normal. The only time I had a positive CRP was before I started wellbutrin several years ago.
  18. lnester7

    lnester7 Seven

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    I have very low TNFs so I guess this would not work in me (I guess I belong to a subgroup?!?)
  19. Sasha

    Sasha Fine, thank you

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    Until you mentioned ice baths, I had forgotten that about 20 years ago in the UK, a doctor wrote in a major national newspaper, the Daily Mail, about a therapy he was trying for ME patients involving cold baths. I think he might have been a rheumatologist but I can't remember and I can't remember his name, either. I thought he was going to do a proper trial but he just seemed to vanish.

    The treatment involved taking cold baths at 16 deg Celsius lasting for 20 mins (?). He advised starting at 23 deg on Day One and gradually dropping the bath's temperature by a degree per day (?) until reaching 16 deg. His full protocol was published, encouraging people to try it - I bet a lot of UK patients had a go.

    At the time, I had been confined to bed for several years and only able to leave it for a total of maybe an hour a day, including trips to the bathroom. I had then (and have now) acute viral-onset ICC/CCC ME.

    The short-term results were spectacular. I improved considerably and within (if memory serves) a few days of hitting 16 degrees, I was able to go for a long walk - a mile? A couple of miles? - outside the home. This held up for a week or so until I caught some new infection (or possibly the originating infection reactivated because I pushed it, who knows) and I was back where I started.

    I kept up the cold baths for 18 more months because, unpleasant (I'm not kidding) as they were, I was desperate. They had absolutely no further effect.

    What was your rationale for mentioning ice baths, Sherlock? At the time I thought the idea was that it was something to do with adrenaline but I could easily be misremembering this - it's so long ago.

    By the way, I imagine there are risks to ice baths, if anyone is thinking of trying them! Like a massive heart attack! :eek:

    I used to play a particular music tape to keep my mind off the pain. If I hear the first song from that tape on the radio these days, it takes me in my mind straight back to that bath. :aghhh: And not in a good way. Ow!

    Edit: I realised I'd perpetrated a bit of a hijack here so I've started a new thread on cold/ice baths:

    http://forums.phoenixrising.me/inde...or-me-to-break-pain-inflammation-cycle.23803/

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