Phoenix Rising supports the Millions Missing global day of protest
Phoenix Rising is delighted to support the demands being made in the ME/CFS community’s first-ever global day of protest …
Discuss the article on the Forums.

Jonathan Edwards : Rituximab

Discussion in 'Rituximab: News and Research' started by Jonathan Edwards, Aug 24, 2014.

Thread Status:
Not open for further replies.
  1. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,246
    Likes:
    31,970
    Nobody knows what the right dose of rituximab is. The original dose recommendation of 375mg/metre squared x 4 doses was based on just how much drug they had in the fridge when they did the pilot study. Over a period of twenty years various bits of evidence have suggested that the dose we use for autoimmunity is roughly right but it is not well established. The current trend for giving two doses for induction is really just based on how much drug you can reasonably give in a day. The spacing apart of two weeks is an artefact of my pilot trial with cyclophosphamide that people have stuck with because they do not know where it comes from.

    BUT, the one thing I would say is that Drs Fluge and Mella are developing the longer term treatment schedule in an extremely intelligent and imaginative way. They are watching exactly what is happening as they go along and adjusting accordingly. It might be possible to get away with a much smaller initial dose but I suspect their follow up doses are pretty much right.
     
    ErdemX, panckage and Gingergrrl like this.
  2. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,246
    Likes:
    31,970
    Rituximab was approved for use in RA in about 2007. The rationale for its use in autoimmunity is indeed still not well understood by many physicians. But when there are hundreds of practitioners using a drug and regularly meeting and exchanging experience practical issues tend to get sorted out. The problem for ME is that physicians who might treat it may not have this experience.
     
  3. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,246
    Likes:
    31,970
    Yes, regular repeats of rituximab are the norm, although in some cases it may be as far apart as three to four years. Judging precisely when to repeat treatment is the most important part of the protocol and one which I suspect many physicians may not understand unless they are involved in the background science.
     
  4. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,246
    Likes:
    31,970
    As far as we know there is no 'too much' rituximab dose. Side effects are not related to dose - they tend to occur early on with the start of the first infusion if at all. From other autoimmune diseases it looks as if the dose is not very critical - it is quite likely that we are giving more than many people need. On the other hand a half dose does not seem quite as good. I wouldn't get worried about dosage at all to be honest. The Kolibri dose is the one I devised for RA, for the sake of simplicity. The Haukeland dose may be a bit less for small people but will be about the same for heavy people.
     
  5. Jonathan Edwards

    Jonathan Edwards "Gibberish"

    Messages:
    5,246
    Likes:
    31,970
    Perhaps I should clarify the situation. Kati is basically right. I will try to sort out some of the further confusions. For anyone who is not aware I will just remind people that the autoimmune dose for rituximab was devised by me for very specific reasons to do with mechanisms of autoimmunity.

    Firstly, there is no significant difference between standard oncological dose and autoimmune dose. The exact dosages may be calculated differently and the total amount may be divided into four rather than two infusions, but there is no material difference.

    Secondly, there is no justification for using a low dose on the basis of 'prudence'. As has been pointed out I have previously noted that the standard dose may be more than a lot of people need to get full depletion for three months. However, to be of much use one needs to deplete for six months and both in routine RA care and in the Haukeland studies doctors have moved towards maintaining B cell depletion for much longer periods, which on balance makes sense, even if there are issues that need keeping an eye on. We also have some quite good evidence for even the standard dose not being as potent as we would really like and not giving full depletion for a small proportion of patients. So justification for reducing the dose would need to be based on a formal dose comparison study.

    We have already heard Dr Beiger and Dr Mikovits talking about low doses of rituximab in a way that indicated clearly that neither of them knew what they were talking about. I strongly suspect that Dr De Meirleir has picked up on this. Giving small doses of rituximab is not 'prudent'. In order to break a cycle of autoantibody production even for a period of months you need complete depletion - both on theoretical grounds and based on experience in particular in lupus. Anything less than about 90% depletion tends to have no clinical benefit at all, as one would theoretically expect. The reasons are to do with complicated immunology. However, it is not too difficult to follow. If a self-controlling system has got into a vicious cycle then gentle actions are more likely to interfere with the remaining good functions of the system than hit the vicious cycle. If you blow gently at a snowball rolling down a hill you do not stop the snowball getting bigger, you just blow away the snow around it.

    Moreover, the real dangers with rituximab are of post-infusion allergic reactions and pneumonitis and as far as we know these are UNRELATED to dose - they occur after the first infusion, even if small.

    So giving small doses for 'prudence' is in my view stupid meddling. I also have reason to be angry about this.When I developed B cell depletion therapy for RA I thought it might do a lot of good but I realised that in the hands of stupid and irresponsible physicians it might do a lot of harm. We went through that with physicians in France and probably Belgium giving rituximab without monitoring adequately. The lesson was learnt but not without harm being done. I consider myself responsible at least in part for harm done by usage of the drug. As a result I am only too happy to act as an expert witness for the plaintiff in cases of negligence in relation to inappropriate use. The very last thing I, and also Oystein Fluge and Olav Meall, want to see in ME/CFS is usage by phsyciains who do not understand what they are doing. I sincerely hope that Dr De Meirleir is not playing around with it.
     
    Hugo and Gingergrrl like this.
  6. BurnA

    BurnA Senior Member

    Messages:
    2,086
    Likes:
    9,863
    This thread is a collection of Jonathan Edwards posts on Rituximab.
    The idea is to provide an overview in one thread for people wishing to know more about Rituximab treatment.
    It is a read only thread, if you have questions or comments on a particular post please refer back to the original thread where the post was copied from.

    Thread is currently in progress 06 May 17, please check back when completed.
     
    Last edited: May 6, 2017
    deleder2k, Persimmon, ErdemX and 6 others like this.
Thread Status:
Not open for further replies.

See more popular forum discussions.

Share This Page