ME Research UK: An immunosignature assay for rituximab therapy? [Funding announcement]

[RogerBlack]

8% is better than the 33% that the stage 2 trials show don't benefit from Ritux. And instead of 67% benefiting, 92% should benefit instead - those are definitely significant numbers, IF this test is proven to be accurate.

Viewed from one angle.

Instead of 67% benefiting, 58% (or so) of the input patient population benefit.

You've admittedly saved on drugs, and side-effects/harms, but you've also excluded some who will benefit, and a more nuanced analysis is needed to see if the harm of doing that outweighs the harm of overtreatment of those who will not.

 

[AndyPR]

Viewed from one angle.

Instead of 67% benefiting, 58% (or so) of the input patient population benefit.

You've admittedly saved on drugs, and side-effects/harms, but you've also excluded some who will benefit, and a more nuanced analysis is needed to see if the harm of doing that outweighs the harm of overtreatment of those who will not.

Well, my original comment was about me potentially going for Ritux treatment, so if I've got the possibility to find out if I'm likely to respond or not before treatment then that's all I'm concerned about.

 

[RogerBlack]

Well, my original comment was about me potentially going for Ritux treatment, so if I've got the possibility to find out if I'm likely to respond or not before treatment then that's all I'm concerned about.

In the context of individual patients getting information, this is a great step forward.

Not so ideal if it's used to prevent consenting patients who may (but are statistically unlikely to) benefit.

 

[Gemini]

Amongst various things that worry me about this approach is that it does not seem to have been tested on any standard disease where one might hope it might give a clear result - rheumatoid or lupus or any other autoimmune disease.

@Jonathan Edwards do you know if ME/CFS researchers have looked at the interferon signature used in RA to predict rituximab response?

New Insight in the Mechanism of action of Rituximab: The Interferon Signature towards Personalized Medicine

https://www.ncbi.nlm.nih.gov/pubmed/21955850
https://www.ncbi.nlm.nih.gov/pubmed/22540992
https://www.ncbi.nlm.nih.gov/pubmed/20722020

 

[Jonathan Edwards]

There is another case though which is if the peptides are related to the ME disease process (I though someone was suggesting this?) in which case the change with the Rituximab patients may explain improvements? Would this give a hint at disease process?

I think there is a potential non sequitur argument here. It raises its head din the context of the autoantibody falls seen in responders in the Scheibenbogen/F/M study. The fact that antibodies have gone down with rituximab does not provide evidence for those antibodies being involved in the disease. Some antibodies will go down in healthy people after rituximab. The levels of autoantibodies in the above study were not that different between patients and healthy controls if I remember rightly. Of course it would be great if we had a handle on autoantibodies sin ME but we do not seem to be there yet.

 

[Jonathan Edwards]

@Jonathan Edwards do you know if ME/CFS researchers have looked at the interferon signature used in RA to predict rituximab response?

New Insight in the Mechanism of action of Rituximab: The Interferon Signature towards Personalized Medicine

https://www.ncbi.nlm.nih.gov/pubmed/21955850
https://www.ncbi.nlm.nih.gov/pubmed/22540992
https://www.ncbi.nlm.nih.gov/pubmed/20722020

My memory is that this suggestion did not really pan out to anything. The authors seem to have got slightly the wrong end of the stick on mechanism of action. I am not quite sure what the interferon signature would tell us in another disease because it may be a marker of the inflammatory effector mechanism of the disease rather than the underlying autoimmune response. It is potentially interesting but I have not heard anything more about it recently.

 

[Demepivo]

*It remains a shame that the ME Association & ME Research UK both have to look outside Britain for institutionsto do research :S

*Plus will the UK Rituximab trial ever happen at UCL, UEA, wherever? *sigh*

 

[BurnA]

Of course it would be great if we had a handle on autoantibodies sin ME but we do not seem to be there yet.

Does that 'yet' imply you expect we will?

 

[Jonathan Edwards]

Does that 'yet' imply you expect we will?

I think there will be some. What percentage of patients that covers I do not know. It may be a small number. It may be a lot more.

 

[Jonathan Edwards]

*It remains a shame that the ME Association & ME Research UK both have to look outside Britain for institutionsto do research :S

*Plus will the UK Rituximab trial ever happen at UCL, UEA, wherever? *sigh*

I don't think they have to look outside. It may be healthy that UK charities fund elsewhere and foreign bodies fund in the UK (NIH funding LSHTM and Solve ME funding UCL).

There is a general agreement by all concerned as far as I know that it is sensible to defer any rituximab trial in the UK until the phase 3 results are available from Norway.

 

[alex3619]

Not so ideal if it's used to prevent consenting patients who may (but are statistically unlikely to) benefit.

I can anticipate health insurance criteria where the result of any test will determine whether or not treatment will be funded. If you are in a low response rate group then you might find the treatment is not covered, even though there is a chance that it will result in improvement or recovery.

Its also important to realize that we need a test, if its at all feasible, to determine who will go into remission and who will need ongoing treatment.

 

[Demepivo]

I don't think they have to look outside. It may be healthy that UK charities fund elsewhere and foreign bodies fund in the UK (NIH funding LSHTM and Solve ME funding UCL).

There is a general agreement by all concerned as far as I know that it is sensible to defer any rituximab trial in the UK until the phase 3 results are available from Norway.

It doesn't reflect very well on UK institutions or researchers that research has to be conducted outside the country.

UCL & IiME made endless promises on Rituximab that have not been implemented. All the while IiME lambasted the CMRC & other for a lack of research progress.

The MEA still have money on the table for any suitable institution that can do a Rituximab trial and got abuse for trying to speed up matters.

Very ill people raised a lot of money without seeing any end product. They are still waiting and they are still ill.

 

[charles shepherd]

*It remains a shame that the ME Association & ME Research UK both have to look outside Britain for institutionsto do research :S

*Plus will the UK Rituximab trial ever happen at UCL, UEA, wherever? *sigh*

Regarding research that is funded by the MEA Ramsay Research Fund:

The vast majority of the research that is funded (and has been funded) by the MEA Ramsay Research Fund is carried out here in the UK

However, if we receive a research grant application from overseas that relates to research that is not being carried out here in the UK, and there isn't anyone here in the UK that wants to do so, and we believe it will help to increase our understanding of underlying disease mechanisms in ME/CFS, then we will consider funding it

The MEA funded research study that has just been published on exercise responses to pain involved researchers in both Brussels and Glasgow

The new study that we are funding on severe ME/CFS (Professor Elisa Oltra et al in Spain) involves blood samples from the ME/CFS Biobank and collaboration with a researcher who is involved in exosome research in Oxford

Overall, I think that this type of occasional international co-operation is very important - so we will continue to consider funding high quality research from researchers outside the UK

Regarding Rituximab:

Apart from having some ring-fenced money (£60,000) in the RRF pot to assist with a clinical trial of rituximab (if anyone ever wants to apply to use it) we don't have any involvement with the proposed clinical trial of rituximab in Norwich

My understanding is that a decision on a UK trial will now be based on the results of the phase 3 clinical trial which is nearing completion in Norway.

I assume that the clinical trial in Norwich will go ahead in 2018 if the results from Norway are still encouraging

If not, is there any point in starting another clinical trial?

CS

 

[Demepivo]

@charles shepherd International collaboration is great but research talent within British institutions should be nurtured & encouraged.

IiME are sitting on a big pile of money and nothing has happened apart from some trips to Norway for people associated with UCL & CPD points for a researcher from Holland.

IiME are good at raising money but can they spend money wisely in the best interests of patients?

 

[charles shepherd]

@charles shepherd International collaboration is great but research talent within British institutions should be nurtured & encouraged.

IiME are sitting on a big pile of money and nothing has happened apart from some trips to Norway for people associated with UCL & CPD points for a researcher from Holland.

IiME are good at raising money but can they spend money wisely in the best interests of patients?

I can only comment on the way in which the MEA Ramsay Research Fund raises money and spends research funding money

If you go to the Research section on the MEA website:

www.meassociation.org.uk

..you will see that the MEA Ramsay Research Fund is (or has been) funding a number of biomedical research studies - the vast majority of which are being (or were) carried out here in the UK

In addition, as you are probably aware, we are also funding a major item of ME/CFS research structure - the ME/CFS Biobank, which forms part of the main UCL Biobank at the Royal Free Hospital in London. This is at considerable cost - over £40,000 per annum.

MEA website Research section:

http://www.meassociation.org.uk/research2015/current-research2015/

UK ME/CFS Biobank website:

http://cureme.lshtm.ac.uk

CS

 

[AndyPR]

@charles shepherd International collaboration is great but research talent within British institutions should be nurtured & encouraged.

Which is what they do.

IiME are sitting on a big pile of money and nothing has happened apart from some trips to Norway for people associated with UCL & CPD points for a researcher from Holland.

Personally, waiting until the results of the Norwegian Phase 3 ritux trials are known seems very sensible to me. And equally, money raising ahead of time also seems sensible, what should IiME do, wait for the results and then start fundraising? Chances are if they did that then the complaints would be about it taking so long before they start their trial.

IiME are good at raising money but can they spend money wisely in the best interests of patients?

Do you have any reasons for thinking they wont? I can appreciate that you might have frustrations at the speed of ME research in this country but you just seem to have it in for those who are making efforts to improve things.

 

[BurnA]

IiME are good at raising money but can they spend money wisely in the best interests of patients?

If the scientists they attract to their colloqiums and conferences are anything to go by I would say absolutely yes.

 

[Demepivo]

When you look at the quantity research & the urgency it is being conducted with in the US, it makes me despair about the endless posturing & turf wars being carried out by the UK charities.

@charles shepherd at least the MEA & MERUK invest in UK research and in a variety of studies. Both have funded the excellent team led by Julia Newton.

IiME don't seem to be engaged in anything currently except badmouthing other charities. They don't even invite Prof Newton to their conference for petty reasons.
*Exasperated sigh*

 

[BurnA]

IiME don't seem to be engaged in anything currently except badmouthing other charities.

I think that is unfair. Their contribution and stance on the MEGA debacle was appreciated by many.
Their conference next month has both Fluge / Mella and Ron Davis amongst others. I think most ME patients would settle for an invite list which included those names.

 

[AndyPR]

it makes me despair about the endless posturing & turf wars being carried out by the UK charities.

Examples please.

@charles shepherd at least the MEA & MERUK invest in UK research and in a variety of studies. Both have funded the excellent team led by Julia Newton.

So you now recognise that the MEA is "nuturing and encouraging" UK research?

IiME don't seem to be engaged in anything currently except badmouthing other charities. They don't even invite Prof Newton to their conference for petty reasons.

Examples please.