Rituximab Phase III - Negative result

[Martin aka paused||M.E.]

I've heard many people say this as a theory (that people with ME don't get sick b/c they do not leave the house and are not exposed) but in my case, nothing could be further from the truth. I am not certain that I am in an ME sub-group, or a different illness, but I have not gotten a cold, flu or traditional illness in almost five years. During that time I was exposed to my (step) daughter, my niece, and other family members while they were sick, including while they had strep throat and all kinds of infections. Even though I use a wheelchair, I was never home-bound and I was at schools, hospitals, grocery stores, restaurants, taking my dog to the vet, etc. I was exposed to everything under the sun (even when my niece had scarlet fever) and I have caught nothing. Not even after Rituximab and technically being immunocompromised.

Okay, then my theory is blown away :-D

 

[bertiedog]

Did I say 'CFS is just like AIDS'?

ME (not CFS...that's a very unhelpful name) is also characterised by secondary infections.
Colds...now that is interesting...it is our immune system that makes us feel like shit when we have a cold. If the immune system isn't working we might just feel vaguely unwell and not really functioning for a long time.

I couldn't have a cold for years but just this last week I managed to catch one from a colleague where I do voluntary work. It started within one day of him standing chatting for over half an hour. My immune system dealt with it within a couple of days but left me with a chesty cough due to the catarrh but I didn't feel unwell. I haven't been able to have a normal cold for so many years I cannot remember the last time, maybe 10 years or more.

Pretty sure its due to the gut protocol I have been doing since September, after all about 70% or more of our immune system is said to be in our gut.

Pam

 

[Jo Best]

Pretty sure its due to the gut protocol I have been doing since September, after all about 70% or more of our immune system is said to be in our gut.

Simon Carding (Quadram Science) hypothesises that autoimmunity in ME/CFS starts in the gut.
https://quadram.ac.uk/targets/me-cfs/

 

[Jo Best]

Article in Aftenposten: https://www.aftenposten.no/norge/i/dd50mz/Nedslaende-forskningsresultat-for-ME-pasienter

Rough English translation below via Anna Mitchell's post in IiME Research Facebook group..

Disappointing Research Outcome for ME Patients

There was great excitement about whether the cancer drug Rituximab would help ME patients. Now the main conclusion is clear.

The whole preliminary findings were presented at an ME conference this week. Researcher Olav Mella at Haukeland University Hospital announced the unpublished findings for the sake of ME patients who were hoping for treatment.

The conclusion is clear: It is not possible to demonstrate the effect of Rituximab on the sample of patients who participated in the multi-center study, called RituxME.

The results will only be published in the spring

The scientific article about the study will probably be published in early 2018, and Mella does not want to comment on the case, or say more about the study now.

Aftenposten has previously written about research that investigates whether cancer medicine can cure chronic fatigue syndrome (ME).

• The patient who recovered: spent a day making dinner for my daughter [ https://www.aftenposten.no/.../For-jeg-fikk-behandling
... ]

150 patients participated in the study. Half received placebo

- Could not let the patient get excited

- Patients who, after disclosure of the study were found to have received a placebo, received them in the study, indicating that we would try to get a new study with rituximab if rituximab proved to have a safe effect. When this was not the case, we could not let the patient group get out of bed for months and wait for the study to be published, says Olav Mella to Aftenposten

• New Network: Fresh ME patients gather

In order not to prevent the study from being published, he cannot provide further information about the results.

- But I said at the meeting that the study result means that rituximab, as we have said repeatedly before, should not be used at ME outside of approved clinical studies. We are still interested in immunotherapy of ME but will not use rituximab if a subset of patients can not be identified, for example, through a currently unknown biomarker.

The researchers continue

Olav Mella says that the research group is still engaged in ME and will continue with both patient-oriented research and research that reveals underlying disease mechanisms.

The study initiated in 2015 had 152 patients from five different hospitals to participate. These received either rituximab or placebo, first two infusions at two weeks intervals, then maintenance infusions after 3, 6, 9 and 12 months, and follow-up for 2 years.

The researchers hoped this study would provide a clear answer as to whether the cancer medicine works against ME. The study was national, randomized, double blind and placebo controlled.

Doctor Maria Gjerpe writes in a post on the blog Mariasmetode that it is terribly sad that one does not have a treatment that can help all the millions of sick patients around the world.

She got involved because RituxME was pre-approved from the Research Council, but research on ME was not given priority in the first round.

- Research on ME is underfunded. The study has cost a total of between NOK 20 and 30 million. As the results were promising from the first stages, there was great interest in researching to verify or falsify if Rituximab could have an impact on a larger patient group. "This probably does not", says Gjerpe.

She started a crowdfunding for the study. 5000 donors from more than 49 different countries managed to get 3.1 million research crowns in just over 90 days.

- It was a record. Far from enough money, but it made more balls start rolling and the study was eventually funded, with many different sources, she writes on the blog.

https://www.aftenposten.no/norge/i/dd50mz/Nedslaende-forskningsresultat-for-ME-pasienter

 

[PinkPanda]

Sometimes I think it would be interesting if we could launch a big PR survey about symptoms and successful treatments... maybe there are patterns to be found just among PR users ...

I think that's a really good idea.
Dr Davis definietly measures a lot of metabolites in the indivdual, I don't know if he also compiles the information from many people and analyses it. Also, I don't think that information will be accessible to us anytime soon.


There are some survey programs, like https://www.surveymonkey.com/
Their analysis capabilities are probably limited, not like some high-tech data analysis programs universities etc. use. The poll-function on PR is limited, but might also be helpful.
If anyone has any experience on survey/ data programs please share!

I think the basic setup would be important. There are endless questions to ask, so apart from basic questions, it would be helpful to have a certain idea of some relevant points to ask beforehand. Like you can see from @Londinium 's post, it might not even be enough to ask for own co-morbidities, you might actually have to ask for medical history of the family too.

Some categories could be basic information (age, gender, disease onset, activity level,..), symptoms, comorbidities (+medical history of family),...
Concerning the issue of an autoimmune subgroup, we might have to have some idea of what to ask for, like other autoimmune diseases, measured anit-bodies, IGG and ANA levels, gut symptoms, gut diagnoses like dysbiosis or leaky gut syndrome,..
Of course we need to keep the questions general to some extent, but without some ideas before-hand, I think it will be hard to find a direction, because there is just so much info and stuff to ask for.
And then we could think of what other markers etc could be interesting for other sub-types. Maybe virus-infections like EBV or disease onset, or wether symptoms are very flu-like. Don't really have an idea on that yet.

If someone wants to set up some survey, I think it would definitely be helpful to have a thread and brainstorm together on what questions might be relevant.

Also, if the surveys are not-anonymous/ identifiable in some form, the collected info could be transferred into microsoft excel and then you could do more surveys later on and add the information to the excel data. Kind of increase it over time.

I use most of my energy for working on my blog at the moment, I could imagine to set something up later on though.
Or maybe someone else is interested, or has some info or ideas.
Even if we don't manage to get any results from the data, I think it would be good to compile some data that is publicly accessible, so that people can get a better overview of what symptoms, activity-levels, comorbidities etc others have.

 

[Martin aka paused||M.E.]

I think the basic setup would be important. There are endless questions to ask, so apart from basic questions, it would be helpful to have a certain idea of some relevant points to ask beforehand.

Yes. As I am a lawyer I don't know nothing about statistics (and science in general) :-D So I wont be of any help... But as far as I know there are some really good users on PR with scientific background, even some with medical/biological/chemical background. To get useful information I think they have to be involved in the design of the survey...

and of course these information wont be reliable due to some disturbing factors (some could have another disease; same problem with some studies out there).

BUT: Maybe the data can be useful at least for brain storming...

 

[pamojja]

If someone wants to set up some survey, I think it would definitely be helpful to have a thread and brainstorm together on what questions might be relevant.

Actually Cort did sort of analyze success stories here:

https://www.healthrising.org/forums/recovery-stories/

Wanted to do the same by analyzing existing success stories on PM in my introduction thread:

http://forums.phoenixrising.me/index.php?threads/am-i-right-here.50197/page-2#post-833081
http://forums.phoenixrising.me/index.php?threads/am-i-right-here.50197/page-2#post-833081
But never got past just collecting them, due to the daunting task of having to analysis so many successes.

 

[Dechi]

There is also a very comprehensive list somewhere of symptoms and treatments and how well they work, made from patient data.

I think it would be easier to google it and add to it than starting from scratch. I just can’t remember where it is...

 

[andyguitar]

The differences in the findings of the trial when compared to reports of many successful outcomes before the trial seems very strange.

 

[MandM]

I've watched repeatedly as the same sledgehammers have been applied to Parkinsons, depression and anxiety, and cancers, with wildly unpredictable results due to these individual differences, and am reminded that people die every day from medications taken as prescribed by their doctors.

Learner - I 100% agree. There is a new company here in Canada that does precision medicine reports - MolecularYou (like Arivale in the US) - and I keep introducing the idea that MolecularYou look at ME/CFS as an area of tailored biomarker-based investigation and treatment (and for other autoimmune disease). They are intrigued, but right now, like Arivale, positioning themselves as optimum wellness/prevention, rather than fixing disease. I feel a little too illiterate to lead a conversation with them about roadmap and how ME/CFS might fit into theirs, but I mention it, as I have a feeling this is where the hope lies.

 

[JES]

The differences in the findings of the trial when compared to reports of many successful outcomes before the trial seems very strange.

Here on PR there was a thread about Rituximab experiences collected, and if my memory serves me correct there was only one person who was significantly helped by Rituximab, and 1 or 2 more that had some level of help. @Gingergrrl looks like she also has some benefit from it, but if I understood correct she has quite atypical CFS. Non-responders were in large majority on this forum.

The other reports I'm aware of are mainly from a couple of private doctors' own words, which I would be skeptical of. And then of course the phase 2 results, but again the sample size was small and some of the responders could have had a spontaneous remission.

 

[Learner1]

Learner - I 100% agree. There is a new company here in Canada that does precision medicine reports - MolecularYou (like Arivale in the US) - and I keep introducing the idea that MolecularYou look at ME/CFS as an area of tailored biomarker-based investigation and treatment (and for other autoimmune disease). They are intrigued, but right now, like Arivale, positioning themselves as optimum wellness/prevention, rather than fixing disease. I feel a little too illiterate to lead a conversation with them about roadmap and how ME/CFS might fit into theirs, but I mention it, as I have a feeling this is where the hope lies.

I think you're right. One of my doctors consulted with Arivale here in Seattle, where they use many of the same tests my doctors and I've been using. They have wanted to start with healthy people, I believe so as not to run afoul of the FDA..."this info not meant to diagnose or treat any disease..."

My CFS doc said he could run the Metabolomics test on me, and I know he has on a few other patients around here, but he said he wouldn't know ehatvyo do with the results. I've wondered if my naturopathic doctor would be able to do more with it, as be seems to direct my chemistry like a symphony of moving parts... Wondering if he could do more with more detailed info.

Could anyone around here post a Metabolomics sample to see what kind of info would be available? @JaimeS is such a thing available? Or is it just too detailed for a person to absorb and begs a computer analysis?

It strikes me if we could have biochemical pathways, nutrient status, immune system info - T cells, B cells, cytokines, antibodies, microbiome, and mitochondrial function, and get them all headed toward normal, or as Naviaux says, move the pathways from winter metabolism to summer, that we might be closer to a cure, at least if we haven't racked up too much irreversible damage.

 

[Jesse2233]

@Learner1

I think the metabolites tested varies by lab. I'd be curious to see a list of what Stanford offers as well as UC San Diego.

Here's a comprehensive database of metabolites (many of which are likely included in untargeted shotgun metabolomic profiles)

http://www.hmdb.ca/metabolites

 

[Gingergrrl]

My CFS doc said he could run the Metabolomics test on me, and I know he has on a few other patients around here, but he said he wouldn't know ehatvyo do with the results.

@Learner1 I can't remember if I told you that I did the Metabolon test but my situation was a bit strange b/c I actually donated the blood for Metabolon, as part of a potential research future study, in 2015 when I was at my very sickest with MCAS and in the hospital. The blood sample was frozen but was never used.

About 1.5 years later, I decided that I wanted my doctor's office to run the Metabolon, knowing it was not a current blood sample, and would not reflect how I was doing at that moment in time, b/c I had already done some IVIG (over a year after the sample was given). My motivation for doing it was to serve as a baseline in case the Metabolon was perfected in future years and I could do it again, post treatments, and we could compare the results.

I spoke with the dietician at OMI 3x (who did consults re: Metabolon results at the time w/patients who were not part of any research study like me). She said that my test results were very abnormal in most sections, and some were REALLY bad but at the time I gave the blood sample in 2015, I had barely eaten any food for weeks b/c I was having constant anaphylaxis. The other part that was interesting was that she said that while my results were really bad and I was clearly very ill, the results did not match what she was seeing in the other ME/CFS patients.

I wish I knew something more specific but I truly did not learn anything that changed the course of my treatment plan. I am not sorry I did it b/c if the test is ever really perfected in the future where the results are transferable into real life treatments, I will do it again to compare to my baseline test.

 

[andyguitar]

I have heard that the Rituximab trial cost $400,000 and was funded by private donations. Is that correct? Sounds a bit high to me.

 

[bertiedog]

t strikes me if we could have biochemical pathways, nutrient status, immune system info - T cells, B cells, cytokines, antibodies, microbiome, and mitochondrial function, and get them all headed toward normal, or as Naviaux says, move the pathways from winter metabolism to summer, that we might be closer to a cure, at least if we haven't racked up too much irreversible damage.

I know the following is nothing like as detailed as you describe above but this is the test I did last Monday with Genova in the hope it will give me lots of relevant information for me to act on -

"The Organix® Comprehensive Profile is a nutritional test providing insights into organic acids and a view into the body's cellular metabolic processes. Additionally, children's reference ranges are designed to provide more accurate pediatric nutritional evaluations. Identifying metabolic blocks that can be treated nutritionally allows individual tailoring of interventions that maximize patient responses and lead to improved patient outcomes.

Organic Acids and Nutritional Testing
Organic acids are metabolic intermediates that are produced in pathways of central energy production, detoxification, neurotransmitter breakdown, or intestinal microbial activity. Marked accumulation of specific organic acids detected in urine often signals a metabolic inhibition or block. The metabolic block may be due to a nutrient deficiency, an inherited enzyme deficit, toxic build-up or drug effect. Several of the biomarkers are markers of intestinal bacterial or yeast overgrowth.

The Organix® Comprehensive nutritional test profile provides vital patient information from a single urine specimen. This organic acids nutritional test is valuable for determining:

• Functional vitamin and mineral status
• Amino acid insufficiencies like carnitine and NAC
• Oxidative damage and antioxidant need
• Phase I & Phase II detoxification capacity
• Functional B-complex vitamin need
• Neurotransmitter metabolites
• Mitochondrial energy production
• Methylation sufficiency
• Lipoic acid and CoQ10 status
• Markers for bacterial and yeast overgrowth"

Pam

 

[Gingergrrl]

I have heard that the Rituximab trial cost $400,000 and was funded by private donations. Is that correct? Sounds a bit high to me.

I have no idea but trials are very expensive and this does not actually sound high to me (at least not for a trial in the US... maybe it is different in other countries)? Rituximab alone is an expensive medication, plus infusion costs for each person for each infusion, paying the trial staff and nurses, the facility fees, pre-meds or post-meds, any emergency care that arose, paperwork and admin costs, etc.

 

[fingers2022]

Yes. As I am a lawyer I don't know nothing about statistics (and science in general) :-D So I wont be of any help... But as far as I know there are some really good users on PR with scientific background, even some with medical/biological/chemical background. To get useful information I think they have to be involved in the design of the survey...

and of course these information wont be reliable due to some disturbing factors (some could have another disease; same problem with some studies out there).

BUT: Maybe the data can be useful at least for brain storming...

If solving ME were a challenge confronting the private sector, it certainly wouldn't be approached by allowing random researchers to come up with random theories. Those most skilled at fundraising would not be allowed to p1$$ everyone's $$$$ away. It would be approached systematically, and that can include brainstorming. Before treatments could be researched and tested, identification and diagnosis would need firm agreement.

A 'big data' approach to all of this would certainly make sense. Surveys are OK, but can often miss key facts as only the questions asked are answered. However the data were collected, it would make sense to structure it so that it could be both quantitatively and qualitatively analysed. Software to do this is well advanced, with its development roots in what we used to call management information systems and business intelligence.

I think if someone could bring together academics/researchers, data analysts, software developers and private enterprise then this could be a fruitful approach. It needs a will and lots of $$$.

 

[Gingergrrl]

A 'big data' approach to all of this would certainly make sense.

I think if someone could bring together academics/researchers, data analysts, software developers and private enterprise then this could be a fruitful approach. It needs a will and lots of $$$.

I'm pretty sure that this is what Dr. Davis and OMF are trying to do but the lack of money is limiting them to a very small sample size and stalling the research. I also suspect (and this is just my opinion) that without a bio-marker and having different sub-groups, it is incredibly challenging to know if all of the subjects in any given study actually all have the same disease.

 

[TreePerson]

I have heard that the Rituximab trial cost $400,000 and was funded by private donations. Is that correct? Sounds a bit high to me.

I am pretty sure I read somewhere that the trial cost around £30 million. I now can't find it - but it was some where in the last few days. Now I am wondering if this was krone or dollars but it was a high figure.