“The Drug” – The Rituximab Story…From the Beginning to the Present….

June 19, 2012

Posted by Cort Johnson

Jorgen Jelstad Norwegian Journalist Covering ME/CFS

Norwegian journalist Jorgen Jelstad has been all over the Rituximab story. His Invest in ME Conference tweets updated us on recent events, in his “How Important is Rituximab?” blog he talked with researchers about Rituximab’s potential and in his  recently blog, “The Drug”, he published a blow-by-blow account of how Rituximab grew to such prominence in the ME/CFS universe.  Thanks for allowing Phoenix Rising to publish the story..Here we give a synopsis of the story and of Jorgen’s recent interview with Dr’s. Mella and Fluge. 

It turns out that it all began almost 10 years when Anne Katrine, a CFS patient with leukemia, walked into Dr. Fluge’s office at Haukeland University in Norway….

 Anne’s leukemia had come back and she’d begun her second round of treatment but this time she had something interesting…even amazing to report; five weeks after starting her latest treatment regimen, the aching muscles, headaches, terrible fatigue, cognitive problems etc. she’d endured for seven long years with ME/CFS had largely disappeared. Amazingly this mostly home-bound mother had gotten so well so quickly that she’d even taken a trip to Turkey with her son. 

Intrigued, Fluge said he couldn’t get her out of her mind and she wouldn’t let him as she prodded him to figure out what had happened. Eventually Fluge, a cancer specialist who had hardly heard of chronic fatigue syndrome, teamed up with the cancer department head, Olav Mella, and they took their shot.

The only thing different in Katrine’s latest course was a drug called methotrexate, a medication that inhibits the immune response by knocking down B-cells. Fluge and Mella recruited two other patients, one of whom was a bedridden patient, Svein, who like Anne, came down with ME/CFS following a viral infection. Now in his 10th year with ME/CFS Svein had trouble carrying out even basic activities and had gotten to the point where he wondered how much longer he could go on. This time they were given Rituximab, another B-cell depleter.

 Six weeks after his first Rituximab infusion Svein responded similarly, rising from his bedside to go skiing and taking hour-long walks, doing carpentry around the house and reading for the first time in years.

“After my first treatment I finished two books in a weekend. Before treatment I could not even read two pages,” said Svein.

Ten weeks after the treatment he crashed and was back in bed. Another treatment roused him again – and lead to another crash. Svein couldn’t be off the drug without relapsing but he was doing better and better on it. The third treatment was the best yet; like Lazarus rising suddenly from the dead, when that one kicked in Svein threw himself in heavy physical work putting putting up a new roof and walls…with no ill effects. He said

“As soon as my body functions again…I’m ready. It is like being brought back to life again”

With all three patients experiencing major improvements Fluge and Mella were convinced the treatments were touching ‘a central mechanism’ in the disorder. They published their results in 2009 and began a small randomized, placebo-controlled trial with 30 patients.

The results of that trial, published in Nov. 2011 were shocking; fully two-thirds of the patients significantly improved while 13% of the group that received the placebo did. The word ‘significant’ can be misleading with sometimes minor gains being reported as ‘significant’ but the improvement in this case was real with 90% of the patients reporting their improvement was ‘major’. The fact that the chronic fatigue syndrome patients followed the same rebound/relapse pattern as people with autoimmune disorders did suggested that not only was the disease legit but that it be an autoimmune disorder.

The results of the study made a huge splash around the world but none were bigger than at its epicenter, Norway, where the government made an abrupt turn around and apologized for years of neglect. As Jorgen explained

 It was like Rituximab was a tipping point for not longer being able to give the impression that this disease was not real, or that it was mainly a psychosomatic problem. Because how do you argue against a big gun cancer drug? In a way, Rituximab did not just heal some of the study participants, it also healed the self-respect of thousands of Norwegian ME/CFS patients who finally experienced something else than suspicion and disbelief.

Fluge/Mella Interview

Jorgen’s talk with Dr’s Mella and Fluge Jorgen (in the Invest In ME newsletter ) shed some more light on what’s going on with the drug right now…. 

Fluge and Mella have been able to use ‘maintenance’ doses of the drug to help patients maintain major improvements for months or even a year and some clues are emerging about what the drug is doing in ME/CFS. They believe that a pattern of symptom worsening, sometimes lasting several weeks, after starting the drug could be an important sign. The fact that B-cell levels aren’t correlated with remission (B-cell declines) or relapses (B-cell increases) suggests other parts of the immune system play a role as well. 

A very variable ‘time response’ to the drug, ranging from six weeks to 8 months, however, is simply a mystery and as always, it seems with ME/CFS, the deeper a researcher digs the more convoluted the situation is. Fluge and Mella are confident in their results….the original study findings are holding up and they “feel confident that at least in a subgroup of patients the pathogenesis at some level will involve B-cells” but like others before them the disorders complexity impresses and they noted “the disease probably is even more complex than we originally thought.”

Expect a few studies to show up after the summer and more as they finish up some ongoing studies.

Fluge and Mella’s Studies – Five studies are underway or in the project planning stage

  • Data Capture Study – Fluge and Mella will be gathering drug to the 28 patients who fell in to the placebo-controlled group and hope to use that data to help them with funding for the ‘big study”
  • Severely Ill Study – Six severely ill patients will get the drug
  • Etanercept – Fluge and Mella will give the tumor necrosis factor inhibitor Etanercept (Ebrel), another autoimmune drug, to a set of patients who didn’t respond to Rituximab/
  • Pathogenesis – Fluge and Mella will dig into their now impressive biobank of samples and try to figure out just what is happening to ME/CFS patients as they get the drug.
  • The’ Whopper’ - Fluge and Mella have always said larger studies are needed to validate their findings and this one; 100 patients in a randomized, controlled trial (RCT) should fit the bill. They are now looking for funding.

More Rituximab

(Jorgen Jelstad is a Norwegian journalist and author of the documentary book “The Hidden Ones: and how ME came to be the most controversial disease of our time”. The book is so far only available in Norwegian – named “De Bortgjemte”. This article was printed in Invest in MEs conference magazine for the 2012 Invest in ME conference. )

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12 comments

{ 12 comments… read them below or add one }

oceanblue June 20, 2012 at 5:20 am

Thanks for that update – it's good there is so much in the pipeline. The maintenance study is very important as the improvement in the 2011 PLoS One paper was modest as patients peaked at different times then fell back.

I was a bit disappointed that the 'whopper' study will only have 100 patients (split equally between treatment and control would give a rather modest n=50). Is this right? It was orginally billed as a large multi-centre trial, so I'd expected something quite a bit bigger.

niall June 20, 2012 at 7:24 am
oceanblue

Thanks for that update – it's good there is so much in the pipeline. The maintenance study is very important as the improvement in the 2011 PLoS One paper was modest as patients peaked at different times then fell back.

I was a bit disappointed that the 'whopper' study will only have 100 patients (split equally between treatment and control would give a rather modest n=50). Is this right? It was orginally billed as a large multi-centre trial, so I'd expected something quite a bit bigger.

Hi Oceanblue, As I understand it, Dr. Klimas, Dr. Peterson, Bateman et.al. will be meeting in New York this week to discuss, among other things, conducting Rituximab trials in the not too distant future.

Cort June 20, 2012 at 12:54 pm

I think its more 150 people from what I read since I posted the article but the number will depend on the funding and on how good Fluge and Mella believe the diagnostic capabilities of the various centers are…..If they're not up to snuff the study will be smaller. They're very wary about false diagnoses.

oceanblue

Thanks for that update – it's good there is so much in the pipeline. The maintenance study is very important as the improvement in the 2011 PLoS One paper was modest as patients peaked at different times then fell back.

I was a bit disappointed that the 'whopper' study will only have 100 patients (split equally between treatment and control would give a rather modest n=50). Is this right? It was orginally billed as a large multi-centre trial, so I'd expected something quite a bit bigger.

oceanblue June 20, 2012 at 1:54 pm
Cort

I think its more 150 people from what I read since I posted the article but the number will depend on the funding and on how good Fluge and Mella believe the diagnostic capabilities of the various centers are…..If they're not up to snuff the study will be smaller. They're very wary about false diagnoses.

That's reassuring, thanks.

taniaaust1 June 20, 2012 at 5:29 pm

thanks for this article..

Any study more then 3 times bigger then a first which got attention, Im happy with, as positive results again can only lead to far more studies by others on this. Others will also need to validate these results before this treatment has any hope of becoming acceptable by our medical profession.

I can only say thanks to the scientists involved in this.

sensing progress June 21, 2012 at 9:02 pm

I didn't see an interview with Dr’s Mella and Fluge in the Invest In ME newsletter. Just the article by Jorgen describing the doctor's discovery of Rituximab as a treatment for ME/CFS. Is that what you are referring to as the interview, Cort?

Enid June 22, 2012 at 1:28 am

Nice to see Cort, I did hear they were restricted by funding (aren't we and they all).

Cort June 22, 2012 at 11:25 am
dsdmom

Thanks Robin. I see her in a little over a week and will be sure to report back here!

It's there – it's a short one – just after Jorgen's article – easy to miss.

Xandoff June 22, 2012 at 4:31 pm

This is a great story, thanks for posting it Cort! Rituximab is definately in our ME CFS future ( I hope). In my best Jack Nicholson voice…".just wait until the pharmaceutical Mob CEO's get a whiff of this"!

Cort June 24, 2012 at 11:10 am
oceanblue

Thanks for that update – it's good there is so much in the pipeline. The maintenance study is very important as the improvement in the 2011 PLoS One paper was modest as patients peaked at different times then fell back.

I was a bit disappointed that the 'whopper' study will only have 100 patients (split equally between treatment and control would give a rather modest n=50). Is this right? It was orginally billed as a large multi-centre trial, so I'd expected something quite a bit bigger.

Dr. Kogelnik of the Open Medicine Institute is started or has started a trial..I believe its an open-label trial – You can find some on studies here….http://phoenixrising.me/treating-cf…uximab-chronic-fatigue-syndrome-mecfs-studies

dsdmom June 24, 2012 at 11:48 am
Cort

It's there – it's a short one – just after Jorgen's article – easy to miss.

Cort, Not quite sure where you got my quote. Is this crazy brain fog or a glitch? Either way, Im not remembering this…

user9876 June 28, 2012 at 6:18 am

I don't know if people have seen the patents that Fluge and Mella have filed but they may also give some insight into how they are thinking of treatments

http://www.google.co.uk/patents?id=…=dUrsT7iIG8j-2QX0lojcAQ&sqi=2&ved=0CDQQ6AEwAA

And a more recent one
http://www.google.co.uk/patents?id=…=dUrsT7iIG8j-2QX0lojcAQ&sqi=2&ved=0CDcQ6AEwAQ

Both are pretty comprehensive around using b cell depletion to treat ME. In the claims they seem to mention quite a few possible antibodys and then talk of a single or multiple doses

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