In a surprise Norway refuses to fund multi-center chronic fatigue syndrome Rituximab treatment trial
Norway Says ‘No Go’ to Further Fluge/Mella Rituximab Funding
It’s kind of inexplicable. Fluge and Mella put Norway on the map of the chronic fatigue syndrome community in a big way, and stimulated interest and efforts from the US to Australia yet the Norwegian Government just announced their proposed multi-center chronic fatigue syndrome Rituximab study didn’t make the cut.
Everyone involved appeared shocked with Secretary General of the ME Association , Anette Gilje, stating they fully expected, given the feedback they were getting , an easy approval. “The signals we got last year was that this was a breakthrough and that it would be followed up, she said.
Even politicians registered their dismay with one parliament member stating “I am furious at the government for not initiating this research project to Fluge and Mella. Nine million is nothing in the state budget” and said she would challenge the awards. Two other ME proposals also didn’t make the final cut
Interest in the study was very high with Fluge stating he’d received hundreds of emails. They’d hoped to start a 140 plus multi-center treatment trial.
This was a big loss; no one else appears to be considering a study of this size and rigor (double-blinded, placebo controlled) and it had a chance to pretty much settle the Rituximab question for ME/CFS. A successful Rituximab study would change things radically; the disorder would be legitimized, immune and autoimmune researchers would jump on board, funding would surely soar over time.
While no one study is definitive, if the study was large enough and it was done right, it would be a game changer. Contrary to our expectations I think many researchers would love to take a bit out of chronic fatigue syndrome if they had a good way ‘in’. A successful Rituximab trial would have provided that.
Mella was good about the rejection, stating that “When the chance is 10-15 percent it’s no surprise when one does not get the money” but it must have hurt…One might think that the chance to blow open the doors for such a mysterious and debilitating condition might have been persuasive…
Patients Punch Back
The flack definitely hit the fan in Norway and it appeared to work. Norwegian journalist Jorgen Jelstad reported that Norwegian Health Minister Store quickly stated his agencies commitment to ME/CFS on his Facebook page. Trying to defuse the dismay Store stated that he would send a letter to (translated) “make it clear that research into the causes and treatment of these disease states will be given priority into the research councils program plans…. In addition we will continue to grant to RHA West and other regional health authorities for the implementation of the planned multi-center study on the treatment of ME.”
That was helpful; it sounded like they were committed to doing the groundwork for the study but doing the groundwork is not doing the study. Store’s Facebook post, though, quickly got around…Five days later it had almost 400 likes and over 80 comments. Store stated the next round for funding will be in Spring 2013.
The Work Continues
Fluge and Mella will shoulder on and work to start the study and said they would be surprised if one didn’t show up next year. The Kavli Foundation has been helpful in the past and the Norwegian ME Association has been working on other funding mechanisms since June and has started a fundraising campaign.
The positive Fluge/Mella findings didn’t mean getting a study going was ever going to be easy. This drug is very expensive and pharmaceutical companies aren’t lining up to spend money on a disorder which they have trouble even describing properly while other ‘easier’, more well defined conditions are available…That’s why, of course, that government, non-profit and private funding is so important.
How We Can Help
The Norwegian ME/CFS groups are at ground zero for Rituximab and there are ways we can help them help us; thanks to Anne for providing information how:
Two Norwegian fundraising efforts are running to raise the funds needed (approx. $1.5 million). They are asking ME/CFS patients and their friends and families around the world to contribute.
- Kronerullingen, fundraising effort by The Norwegian ME Association – http://me-forskning.no/
english/ - MEandYou Foundation, patient driven crowdfunding foundation – http://www.meandyoufoundation.
no/
The multi-center study is set to start as soon as funds are raised, and since public funding may not be available, patients are now aiming to crowdfund the trial. (Should Fluge and Mella be given public funds at a later stage, the money raised in these two Norwegian fundraising efforts will be directed towards other biomedical ME/CFS research studies planned by Fluge and Mella – they have a lot going on)
More on the Norway Situation
- Jorgen Jelstad has been the man on the ground on Rituximab in Norway. Read his take on the Rituximab study rejection and why a study like this is so important.
- Check out the Phoenix Rising Forum thread here
Herpesvirus Researchers Embrace Rituximab Results
Two ME/CFS herpesvirus researchers believe the Rituximab results fit their understanding of the disease
Meanwhile in the conclusions of a small study on EBV persistence in chronic fatigue syndrome, Drs. Lerner and Glazer suggest the success of the Fluge and Mella studies makes sense given their model of an abortive herpesvirus infection in this disorder. They posit that herpesvirus antivirals keep viral replication in check while Rituximab removes the infected B-cells that are pumping out herpesvirus proteins).
Several ME/CFS doctors, including Dr. Kogelnik and Dr. Lerner, believe Rituximab’s success in this disorder is more likely due to antiviral effects instead of the autoimmune suppression ordinarily associated with this drug. Despite searching for three years for biomarkers Fluge and Mella have reportedly been unable to find evidence of an autoimmune process occurring in ME/CFS.
Analysis Suggests Rituximab is Safe Drug….in Rheumatoid Arthritis patients
Rituximab (Rituxian) – first developed as a chemotherapy drug and like most chemotherapy drugs it can pack a powerful punch, good and bad. It’s safety information states it can cause such serious problems as activated hepatitis B and other serious infections, heart problems, progressive multifocal leukoencephalopay, tumor lysis syndrome, low blood counts and more..
Thus far the ME/CS patients taking the drug under Fluge and Mella appear to have escaped serious problems but the spectre of dangerous side effects persists – particularly in such a disabled population. Given Rituximabs immune suppressing properties the prospect of serious infection probably looms largest…
A analysis of over 1,000 Rheumatoid arthritis patients on Rituximab brings some good news. For one, the risk of serious infection didn’t pan out; Rituximab didn’t increase the risk of infection nor were heart attacks or cancer more likely.
At present Rituximab is too expensive and not widely enough available for many people with ME/CFS to get but it will be going generic in the next year or so…While chronic fatigue syndrome is not rheumatoid arthritis and effects may differ ME/CFS patients on the drug, and those expecting to try it at some point can take heart that serious side effects appeared to minimal in another large population.
Patient Blogs
Several patients on Rituximab are reporting on their experiences…
- Jacque – at week 18 Jacque has gotten the munchies but is feeling no better but recognizes that 18 weeks may be too little for improvement to show up; five months is common…
- DSDMon – is on week 13 and has had some trouble with side effects and has seen no positive results as of yet but again this drug in ME/CFS and other disorders can take quite a while to work
- Rituximab Tourist – is over 8 months in and is actually getting worse, not necessarily because of the Rituximab , but she’s seen no positive effects as yet. She has another infusion in January and hopes she may just be a late responder.
The Poll
Would you take Rituximab? With about 110 replies, the results from the Phoenix Rising Poll has about 53% saying yes, 23% saying no and 24% not sure.
SUPPORT HEALTH RISING
The question that pops up in my head, is what can we ( a broad term used to incorporate the me/cfs community) do to be proactive in advocating for this crucial work ?
That’s a great, great question….The proposed study was 9 million dollars (I guess US)…Norway is ground zero for this..No other country that I know of is proposing a Rituximab/CFS study – the US is certainly not; they seem to rely on drug companies to do that…so a Norwegian study is really a big deal. The Norwegian ME/CFS community hit back hard and it seemed to have an impact. I think we should support them as much as we can…
In the US the Open Medicine is proposing or is actually engaged in a study – I’m not sure which… I’ll find out from Dr. Kogelnik what the OMI’s plans are….PHANU in Australia has proposed one as well.I just talked to Kim McCleary in the CFIDS Association – they are very interesting in figuring out how to do clinical trials more cheaply…This makes sense given the Drug Repurposing Study should be completed in the next 4 or 5 months and they will have some new options on their hands…..Lots of advocates for other diseases are looking into this – the clinical trials process is just way too costly…there is something of a push to find ways around it going on.
Actually, they/we need “only” about 1,26 million USD, 7 million Norwegian Kroner. They originally needed 11 million NOK, they got 2 million when the news broke in 2012 and our new health minister Jonas Gahr Støre has confirmed they will get another 2 for 2013. So, spread the word everybody! We can do this! 🙂
Great news…There’s a solid foundation to build up – that’s very important. The more money they get the more reason to do the study..(Why not finish a study that you’ve put X million kroner into?) Thanks
If i understand it correctly: The old minister gave them 2 million when the news broke, the new one continued the same support for 2013. But by the time he became helath minister, Fluge and Mella had allready applied to the research council, and he (and the rest of the politicians) thought that they would get the funding from there (where i guess they’re supposed to). There had been broad political aggreement to prioritize ME-research, and signals had been sent to the research council. He, among others, was surprised when the reseach council didn’t prioritize this, although they said it met their primary criteria: quality.
Side note: They also didn’t prioritize another ME-study (stress-management or something, by Vegard Bruun-Wyller) they also stated had high enough quality, using Klonidin/Catapresan. Also, a study of Lightning Process lacked funding (no mention of quality here from what I’ve seen). So, no studies on ME made the cut this time.
However, the budget for 2013 was due to be voted on and passed just a few hours after the Research Council announced this, and Støre wouldn’t change the budget at that stage. He also mentioned the disagreements between researchers and not wanting to decide this as a politician. (altough, his predecessor, in a way, did this when she gave them 2 million in the first place, and he continued this practice). So, it seems they sort of fell in between things this time.
I really hope they/we get this show on the road as soon as possible, we need this! If the results are consistent with the smaller scale-tests, I hope and think we’re a lot closer to a treatment, or even a cure! 🙂
I suggest maybe some study is set up to study this on a world level. That ME/CFS patients who are about to take this drug (the lucky few who have money to do so and have been able to convince their doctors) enrol in a set up study just before their infusions and those patients then studied.
Ive heard of a few ME/CFS patients starting this drug and its a pity these people werent enrolled in a study.
Agreed. As we’ve seen with Ampligen studies are critical. The Scientific world does not listen to anecdotal reports. But it does listen VERY WELL to well-designed studies…Those types of studies can change things big time..
I just added some information to the article on how to help the Norwegians get the study going…Thanks Anne for providing that.
Here’s a theory from Kasper Ezelius regarding why the Lerner theory of ME/CFS and the successful Rituximab results make sense.
Hypothesis:
http://www.plosone.org/annotation/listThread.action?root=58277
My idea is that the body has an immune reaction to viral proteins/enzymes (EBV dUTPase and EBV DNA polymerase) produced by infected cells. My idea is that EBV virus reside in for example myocytes (muscle cells) and pump out these enzymes at an increased rate during physical activity. Antibodies attach to these enzymes and this starts an immune reaction.
Rituximab would reduce the amount of enzymes that attach to the EBV enzymes. Nevertheless, the EBV viruses will still produce them where they reside inside myocytes (or other cells that they may infect).
This hypothesis may explain why the effect of rituximab has a delay of several months (life span of antibodies).
Some examples of cells that EBV can reside in are: plasma cells, NK-cells, T-cells, myocytes and epithelial cells. The intestines are covered with epithelium (made of epithelial cells), and maybe EBV reside there, and this is one explanation why many ME-patients have a sensitive stomach. Maybe the EBV enzymes (dUTPase and DNA polymerase) released causes an immune reaction with both local and systemic effect.
The hypothesis where the effect is thought to be due to rituximab causing the B-cells to die off and therefore also the EBV virus inside them, does not explain why the long delay of clinical effect. The B-cells are almost immediately depleted within a few days.
/Kasper Ezelius, Sweden
1. Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset
Martin Lerner et al 2012
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047891
There are reports from a few Norwegian patients who have improved substantially on Rituximab. Recently an article was published in one of the major newspapers in Norway which described four patients who have seen major improvement with Rituximab – these patients are either participants in the Fluge-Mella studies or pilot patients for the coming study. (But the article also includes two Norwegian patients who have not had access to Rituximab in Norway and have opted to travel to Kogelnik in CA, but have not seen any positive effects.) So far, the 2/3 ratio of responders seem to hold up, though the positive effects vary in strength and Fluge and Mella are finding out how to best create a maintenance treatment to keep the positive response going.
The article can be seen here – in Norwegian, though… 🙂 Headline: Hoping for a miracle
http://me-foreningen.com/meforeningen/innhold/div/2012/12/ME-A-magasinet.pdf
One of the patients who have responded really well is Maria Gjerpe, a well-known and much respected ME/CFS patient, physician and blogger. She has gone from being quite ill with ME/CFS to functioning at 80%, close to feeling completely healthy. She tells about her experience in her blog “Marias metode”, and she usually puts in an English summary in the blog post (sometimes you need to scroll down to find it):
http://mariasmetode.no/2012/12/rituximab-for-me-jeg-er-pilotpasient/
http://mariasmetode.no/2012/12/6-maneder-pa-rituximab-tur-6-months-on-rituxan-tour/
http://mariasmetode.no/2012/12/rituximab-for-me-hapet-om-et-mirakel-i-a-magasinet/
Maria Gjerpe is also the founder of the fundraising initiative “MEandYou Foundation”, one of the two Norwegian initiatives which have set out to crowdfund the planned multicenter study by Fluge and Mella. Please contribute to the MEandYou Foundation here (donations are easily made through PayPal):
http://www.meandyoufoundation.no/
Fluge and Mella are also studying other drugs in the 1/3 of patients who did not respond to Rituximab. These two brilliant oncologists have put their minds and hearts to solving the ME/CFS puzzle. So far they have been working evenings and weekends with sparse funding – we should do everything we can to keep them in the field and give them the funds and the team they need to carry out all of their planned research!
Thanks for that wealth of information, Anne :)..
What about all the work looking at the link between FMS and ADHD-Innatentive type? There seems to be quite an overlap in symptoms and possible causation. If you are diagnosed with ADHD, you can have a stimulant.
Hi I put my money on Dr. Don Staines and Prof. Sonya Marshalls – vasco active peptipe theory that they talked about at ME Invest in London in June.
This theory explains all the symptoms of ME and even why rituximab works.
However Don said that the use of rituximab is liking hitting a walnut with a sledge hammer and he thinks with time once the actual peptides involved are identified (why they urgently need a new flow spectrometer at Griffith University)much more refined drugs will be able to be used. In the meantime we only have a sledge hammer. In the meantime at least we have a sledge hammer.
to understand the real cause of ME should have known because an influenza vaccine with a strong adjuvant as pandemrix, why? simply because the activation of disease is very brutal; stronger than in a natural natural following viral infection onset… those who have developed ME after the pandemic 2009 H1N1 vaccination have mostly known an attack at the level of the cerebral trunk and spinal cord, this will not collect in natural forms, the victims of this vaccination with PANDEMRIX before all a very severe form of ME, and we surely all receptive to rituximab, which can in europe offer us off-label treatment? and for how much? We are at the moment more than 20 sick people, européens(anglais, irlandais, français, suedois…) have this filth of disease after a vaccination is unacceptable, we are looking for a doctor in europe to treat us… go in California is still a bit far away, you will find my face book page: “GSK WAR GULF ILLNESS”