What is the ME Association doing about Rituximab? Statement 8 July 2013

I am rather laid up today - but you might all like to read the statement in full that was posted this morning. Dr Shepherd is taking questions on the MEA Facebook page at the moment if you have any.

It does go into a lot of detail about the regulatory hurdles and likely costings etc. Haven't read all of it myself but will try and come back to it later.

Dr Shepherd just posted a link to Rituximab in Myostis from the Myostis Association, that I shall read later. Appears to contain some perhaps relevant observations that Ritux might be more effective in sub-groups:

There are 32 comments relating to the MEA Rituximab statement now on the MEA Facebook page. I need to catch up with those too I think.

I believe the MEA have written to IiME and all the other ME Charities to hopefully get the ball rolling further on some sort of collaborative effort for clinical trials.

Quite liked the notion of trying to discover why patients respond to the drug and trying to better understand who might benefit before applying a scattergun approach.

Would make sense if patients receiving this drug were the ones most likely to benefit. Be interesting to also learn how those who test as likely benefit are different from the rest. Is it a defining characteristic of 'ME' or something else? Can you develop 'autoimmunity' if that is what we are talking about during the illness aka 'ME'?

Quite fascinating.

If its the same artilce with dr shepherd, there was alot of arguing over xmrv etc in the question and answer section. An outsider looking into this, it wouldnt have been a good look. both sides seem to be at each other.??
the actual article was interesting.

Not sure what you mean here, heapsreal. Can you clarify? I can't seem to find any arguing either on the MEA website or their Facebook page. Indeed the Statement and Q&A looks to have been very productive.

Sorry cant clarify. Cant remember where I saw it. Apparently some cfsers took offence to dr Shepherd saying xmrv is unlikely as there is poor science backing up xmrv existence. The q and a I saw was basically about that and got way off track about rituximab. The q and a was under the initial article. It may have been on the other cfs site thats very pro retroviral cause of cfs but I cant remember.

Rituximab side-effects are scary.

I expect that Rituximab is only effective if it's the B-cells where the herpes virus is hiding out, i.e. in the case of EBV-induced ME.

I just dont know. I think we mostly have chronic infections everywhere and rituximab lowers our immune function. Ebv etc might be in b cells but they also hide out in our nerves and brain etc. Unless they can say that one has no infections and its definately in b cells then I would wait for further research. I think we will find an auto immune subset to go along with the different herpes sub sets and bacterial subsets and mixtures of these. I would like to see combo therapies like avs and ritux as well as avs and ampligen. Also I think what might be important in all this is the pathogen studies??

The Open Medicine Institute top priority study is a 2x2 RCT of Valcyte with Rituximab (i.e. in combo, singly, and neither), presumably looking at exactly the hypothesis that you've got to wipe out reservoirs as well as resetting the system.

From Charles Shepherd earlier on ME Association Facebook. Relevant to the MEA 'Ring-Fenced' funding pledge the other day; their earlier statement about Rituximab; and to yesterday's statement from IiME regarding Professor Edwards and UCL.

Good statement. As far as the last bit goes:

Positive results from Norway plus a positive result from a small clinical trial in the UK will definitely help to take this process forward but will not be enough

This is just the start of what is likely to be quite a long process of establishing (or not establishing) a new and important use for Rituximab........​

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I think that's right but that we should remember that the UK trial is part of an international effort to get Rituximab trials up and running - just because that trial won't be sufficient on its own doesn't mean we shouldn't support it. We should!

Here's a little more from Charles yesterday on Facebook about how the Ramsay Research Fund (the research fund arm of the MEA) goes about funding projects in the context of the above:

There is evident 'confusion' and a little niggling to be fair not least on Facebook in respect of the IiME fundrasing and the pledge from the MEA of £60,000; as the two charities have both separately been consulting with Prof. Edwards and UCL.

A little more from Charles Shepherd in response to a related question - again on Facebook yesterday - although the 10 points above do spell out again a willingness/need to collaborate if the large sum is ever to be raised in a reasonable time frame:

Dear All,
I am sorry if there is any sense of confusion here. To my mind it is straightforward. We are trying to find a way to set up a rituximab trial, because it may have several long term benefits for people with ME. IiME take the credit for having knocked the right heads together and got them thinking of getting something up and running - pretty impressive to my mind, because there are all sorts of reasons why those people might choose some easier things to think about! So now what we need is for everyone to do what they can. Dr Shepherd has indicated his enthusiasm for doing what he can. If we can get the MRC interested now or later that will help. And questions and critical comments about trial design are being helpful too - the more heads bash together here the better. I will probably post some further comments on the other thread about the study when I get time. I appreciate that people want to know everything at once, but those who are keen to actually get something done need a little thinking space. There is a lot of work to do, but that is not to say that protocol writing has not started. The general shape of a feasible trial looks fairly clear.

Last time I tried something like this I got it done. My role is different now but I would like to see this fly. What I do not want is anyone, be they patient or doctor or charitable donor, get involved in something in a way they later feel they should not have. That can be complicated but it has to be got right. I am not a great believer in the value of formal rules and procedures (a lot of innovative work gets done hand to mouth) but I do believe in making sure nobody is hard done by. Things will take time and everyone needs to be happy, but a lot has happened since June and I would like to see the momentum continue.

Best wishes to all

Jo Edwards

Welcome to the forums, Jonathan Edwards - this is a fantastic thing you're doing for us. I'm very excited about the possibility of a UK Rituximab trial.

Thank you!

Jonathan Edwards, a big welcome to the forum, and thank you for taking the time to clarify some issues.

Jonathan Edwards. Thank you indeed for joining with the wonderful Invest in ME to try to bring this project to fruition. They are such wonderful guys who do such sterling work for no recompense whatsoever. As a member of the 'Let's Do it for ME' team of patients who are attempting to fund-raise to get this trial up and running, I have to say I'm spurred on by having someone of your calibre to advise Invest in ME and help create these trials in a way that can produce meaningful results..whatever those results may be. Other work using dubious criteria for our disease has left us in something of a no-mans land, and we desperately need the good brains that you and Invest in ME can bring to this venture.

Last day to donate to the trial and get it matched pound for pound - about £250 to go, I think (ignore the total on that page, that's their long-term total):

http://www.justgiving.com/onedayonepound

Apologies for cross-posting!

Posting with permission from the author ...simply to clarify the real timeline of events surrounding the genesis of this planned trial, and in the interests of fairness. (Originally posted on the MEA Facebook page in response to comments made by Charles Shepherd).

Charles: This isn't about who takes credit, or who did what when or spoke to whom, it's about getting high quality research done to help as many of us as possible as soon as possible. However, the fact is that Invest in ME and their supporters - patients, parents and carers - have worked hard to achieve this level of interest and enthusiasm and investment of time, effort and resources, from 1st class researchers. The ME community deserves honesty and clarity, so now that Professor Edwards has made his position clear in a full statement and in his comment on Pheonix Rising, can we clarify a few points here once and for all, and I know you'll correct me if I'm wrong.

1. The instigation of the proposed rituximab trial at UCL had nothing to do with the MEA or any other UK charity or group or the newly-formed UK research collaborative. This opportunity arose from the 8th Invest in ME conference events at the end of May 2013. Dr. Jo Cambridge of UCL had significant input to the meeting prior to the conference. The meeting was attended by over 40 biomedical researchers from 9 countries. Professor Edwards attended the IiME conference the following day.

2. You were unaware of the proposed UCL trial when you published your statement in July announcing the ring-fencing of £50k from the RRF for a possible future ritux trial, and inviting further donations for a trial that you did not have in the planning stage and which you knew and stated may never happen. From the minutes of the Forward ME Group meeting held on 2nd July: "On Rituximab Dr Shepherd said that people were raising money for a trial in the UK, and the MEA would be putting out a statement the following week. The problem was that so far no-one in the UK wanted to do that research".

3. You were aware at that time that IiME had announced on 6th June that they were raising funds for a trial that they were arranging. You did not contact IiME prior to publishing your statement and made no mention of their announcement or any planned UK rituximab trial in your statement, nor in the statement published by Tony Britton re-announcing £50k in the ring-fenced MEA fund.

4. Tony Britton's statement was published a few hours after MEA Chairman Neil Riley had said on the old MEA Fb group that he knew nothing of a UK trial, and had been told that the research team would be announced shortly, in reply to his query about which researchers were involved. This was under a post announcing a matching donation period by Let's do it for ME for the ritux trial as part of our 2nd birthday celebrations. No mention was made of either the achievements or even existence of the ldifme campaign, let alone this opportunity to have donations matched, given that it's all for the ritux trial.

5. Your discussion with Prof. Holgate at the UK Research Collaborative was about the general possibility of a ritux trial, not about this particular trial, as you were unaware at the time that a trial was being planned at UCL and unaware of Professor Edwards' involvement.

6. Professor Edwards clearly states that his interest in ME/CFS was sparked by attending the IiME conference at the end of May 2013. You told me that you had spoken with him quite some while ago, after the Phase II Fluge and Mella research had been published and you have said right up until you knew that a trial was being planned at UCL that you had no researchers interested. When I told you of the announcement by IiME that Professor Edwards was acting as adviser to the charity on all aspects of the planned ritux trial (the research team had not been announced), you told me that would contact him to update him on what the MEA were now doing. When I gave you the link to the statements by Professor Edwards and Invest in ME, you told me you then phoned Professor Edwards.

So, to clarify your previous comment that both charities were raising funds for a ritux trial and both charities were being advised by Professor Edwards, as this was misleading. You were raising funds in case of some possible future trial, Invest in ME were raising funds for a trial they were organising. Professor Edwards had given permission for IiME to announce that he was acting in an official capacity, in his retirement, as adviser to the charity, you only rekindled your contact with Professor Edwards once this had been announced. I don't know why you have gone about matters this way. You say you want collaboration, yet you behave as though you are in competition. Let's do it for ME has been all about positivity and progress, we've criticised no-one, even for blatantly copying us instead of supporting us, as we take the view that imitation is the most sincere form of flattery, but enough now.

Let's wipe the slate clean, be honest and fair about the facts and chain of events, and help this excellent team of people who have already been working together with Invest in ME since the May conference, to get on and do their work, which is entirely for all our benefit and with the mutual benefit of collaborating with Professor Mella and Dr. Fluge. Of course, the UCL team can submit an application to the MRC, they are not inexperienced and they have a dedicated Clinical Trials Unit. This should be about the quality of the proposal, of which we patients supporting it are 100% confident. However, we know that high quality proposals for biomedical ME research have been turned down in the past, including an application by a Fellow of the MRC, so we won't hold our breath on that, and let's face it Charles, you say you have discussed with Professor Holgate but we know that such discussions often come to nothing and when they do, it takes too long as there is no sense of urgency. It took 3 years for the MRC Expert Group, in which you and Peter Spencer were involved, to come up with a list of symptoms to be studied, ostensibly to investigate possible causes of ME/CFS. Have things really changed now that the group has a new name with a not so new Executive Board? Let's see shall we, but not wait, we've done enough of that spanning decades now and too many of us are no longer here to tell the tale and reap the potential benefits of this breakthrough research.