New Rituximab ME/CFS open-label phase II study with rituximab maintenance treatment

[Sasha]

The Norwegians were pretty thorough in their immunology. They may not have published all of it because they found very little. It sounds as if Dr Nath may not have talked to them directly, which I would have thought was essential prior to starting a study like this.

Another thing to add to the list for things we'd like Dr Nath to be aware of.

 

[BurnA]

If we get to 2018 and the phase 3 results are similar to the phase 2 results but no biomarker has been identified by then, what will happen from a research prerspective ?

Will it be all hands on deck to unravel the puzzle of why RTX works or will things just tip along as before?

 

[Snow Leopard]

If we get to 2018 and the phase 3 results are similar to the phase 2 results but no biomarker has been identified by then, what will happen from a research perspective ?

If the phase 3 results are similar then there will be a lot of attention! New people coming into the field to try and explain why it is working. Perhaps someone will win a Nobel prize!

 

[perrier]

If the phase 3 results are similar then there will be a lot of attention! New people coming into the field to try and explain why it is working. Perhaps someone will win a Nobel prize!

If we get to 2018 and the phase 3 results are similar to the phase 2 results but no biomarker has been identified by then, what will happen from a research prerspective ?

Will it be all hands on deck to unravel the puzzle of why RTX works or will things just tip along as before?

Yes, but it's such a long time. First we have to get through 2016, then 2017, then 2018. In the meantime so much suffering, so much despair,so much life lost

 

[Kati]

Yes, but it's such a long time. First we have to get through 2016, then 2017, then 2018. In the meantime so much suffering, so much despair,so much life lost

It's frustrating because good science takes time and bad science takes even longer to be erased.

We are living every day 'in the meantime'. More research is needed, more funding, more physicians and more government representant needs to be educated. Let's get to work!

 

[Jo Best]

I haven't read through all the recent comments so forgive me if this has been referred to already - that the paper on the initial B-cell study in the Invest in ME Research has now been published in hard copy (sorry, error, it was published in an early view of the journal not hard copy yet). I mention it here as this work is being done in close collaboration with the Norwegian team and is adding value to the Phase III trials. Collaboration on the rituximab-related studies also includes researchers in Spain, Sweden and Germany. It will be, hopefully, be further facilitated by the European ME Research Group, formed in 2015 by the European ME Alliance, and as usual, by the Invest in ME Conference & Colloquium events, where the Norwegian rituximab research is presented and discussed. This UK research is being crowdfunded and a blog was posted by Let's Do It for ME today - http://ldifme.org/first-paper-published-from-iime-funded-research/

 

[Sasha]

I haven't read through all the recent comments so forgive me if this has been referred to already - that the paper on the initial B-cell study in the Invest in ME Research has now been published in hard copy.

Hi Jo - do you mean it's been published in a journal?

 

[John Mac]

@Sasha I think this is it

Preview. (The abstract requires a login)

http://www.readcube.com/articles/10...iley.com&purchase_site_license=LICENSE_DENIED


Abstract
http://onlinelibrary.wiley.com/doi/10.1111/cei.12749/abstract

 

[Bob]

Hi Jo - do you mean it's been published in a journal?

Yes, in the hard copy journal as opposed to online only.

 

[Scarecrow]

When it was first published online, it was discussed here:

http://forums.phoenixrising.me/inde...ts-with-me-cfs-a-cross-sectional-study.41743/

 

[Jo Best]

Hi Jo - do you mean it's been published in a journal?

Hi Sasha, apologies for the error, apparently, it was published in an early view of the journal not hard copy yet.

 

[wastwater]

Is there a pre,pre leukaemia.

 

[Murph]

I've just been re-reading this paper and noticed they treated one person with ofatumumab and got a clinical response. searched this whole site, and @Snow Leopard 's mention of it above was the only one I found.

These anti b-cell therapies are the best option we've got at the moment, and this morning I was only aware that Rituximab and Cyclophosphamide had been tried. Good to know there's at least one more lurking out there that the Norwegians are aware of!

Seems ofatumumab can sometimes get into those hard-to-reach places Rituximab can't. https://www.ncbi.nlm.nih.gov/pubmed/25964296
A possible alternative for non-responders?

 

[Snow Leopard]

Seems ofatumumab can sometimes get into those hard-to-reach places Rituximab can't. https://www.ncbi.nlm.nih.gov/pubmed/25964296
A possible alternative for non-responders?

I'm not sure how Ofatumumab can "get into those hard-to-reach places Rituximab can't."?
The major difference is that this one is fully humanised, rather than chimeric and of course has many years of patent protection left.

Enhanced in vitro complement-dependent cytotoxicity activity is interesting, especially when your bosses want reasons to market a new drug's superiority over the old drug, but improved efficacy can only be demonstrated in clinical trials. Rituximab doesn't seem to have a problem in depleting B-Cells in most patients so...

Also, perhaps it may also lead to higher risk of side effects...

 

[Murph]

I'm not sure how Ofatumumab can "get into those hard-to-reach places Rituximab can't."?
...

I got the sense Ofa could kill some b-cells with low cd-20 levels? I interpreted the paper as saying it could get some mcl lines that showed "a high degree of in vitro resistance to rituximab associated with low CD20 levels and/or high expression of complement inhibitory proteins."

Just trying to put this into terms my brain can remember easily! I've no idea how common low cd20 markers might be, nor how clinically relevant in me/cfs. I'm sure it has some upsides and some downsides and the fact Haukeland hospital is using Ritux preferentially suggests the balance is in that drug's favour.

I very much take your point that it might well be being developed for profit reasons. And yet, might big pharma sensing some $ be just the trick for getting money put into a bit more cfs research?!

 

[Snow Leopard]

I got the sense Ofa could kill some b-cells with low cd-20 levels? I interpreted the paper as saying it could get some mcl lines that showed "a high degree of in vitro resistance to rituximab associated with low CD20 levels and/or high expression of complement inhibitory proteins."

Yes, but that doesn't mean Ofa will be any better in vivo.

There are claims that Ofa has tighter binding affinity, but clinical evidence is required as to whether this is actually useful in patients or not.

I don't really know anything specific about the low CD20 phenotypes that you are talking about and whether they are important in the perpetuation of autoimmune illness (it's a good question for the likes of Edwards or Cambridge).

 

[Jonathan Edwards]

I got the sense Ofa could kill some b-cells with low cd-20 levels?

The relevance of low CD20 levels only really applies to tumour clones derived from B cells that may have lost most of their CD20 expression - some high grade lymphomas. In autoimmune disease there is no reason why individual B cells should have low CD20 expression.

If we are looking for the best anti-B cell antibody now available we are talking about new generation antibodies with fucose groups and such like. Ofatumumab has been around for at least a decade and we have no evidence it is better than rituximab in the clinic. Probably because it tends to engage complement more it tends to have more immediate adverse reactions from what I can see.