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More is Better: Rituximab Trial Boosts Hopes for Chronic Fatigue Syndrome

The Rituximab  Story

“I was completely revitalized. Suddenly, I could be sociable again. I would go to work, go home, eat dinner and feel restless.” An ME/CFS patient in the study

The Rituximab story started in 2004 when Fluge and Mella two Norwegian oncologists noticed that some of their cancer patients with chronic fatigue syndrome were doing very well on a drug called Rituximab. In fact, they were doing too well. Not only had their cancer gone into remission but so had their chronic fatigue syndrome symptoms.

tweaking treatment protocol RItuximab

In this study Fluge and Mella tweaked their original treatment plan to produce more powerful and lasting results

Fast forward 11 years, one case series and another study later and we find Fluge and Mella not just treating ME/CFS patients with Rituximab but aggressively tweaking their formula to achieve a lasting remission in the responders and to provoke a remission in treatment resistant patients.

In the initial Rituximab trial published in 2011 Fluge and Mella gave 30 chronic fatigue syndrome patients two Rituximab infusions  two weeks apart and then followed them for 12 months. Three months into the trial there was no evidence the drug was working but 6-12 months later two-thirds of the participants had responded and some had responded in truly dramatic fashion. Years of disability and pain dropped away as some patients almost miraculously achieved normal lives.

Many of the responders, however relapsed later. In this study Fluge and Mella tried to do something about that. They gave Rituximab to 29 ME/CFS patients more often and for longer and they followed them for longer.

Rituximab

Rituximab induces B-cells to kill themselves by attaching to the CD20 receptor on them. It also enhances the ability of natural killer cells to kill them.

Originally developed and FDA approved to treat cancer (lymphoma) Rituximab is also FDA approved to treat rheumatoid arthritis and is used off-label to treat multiple sclerosis, lupus, chronic inflammatory demyelinating polyneuropathy, autoimmune anemia, Sjogren’s Syndrome and many others.  Chronic fatigue syndrome may be the first disease outside of known autoimmune disorders, that Rituximab has been tested in.

The Study

B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment. Fluge Ø, Risa K, Lunde S, Alme K, Rekeland IG, Sapkota D, Kristoffersen EK, Sørland K, Bruland O, Dahl O, Mella O. PLoS One. 2015 Jul 1;10(7):

After the two infusions in the first two weeks (500 mg/m2 (maximum 1000 mg) Rituxmab was given four more times at 3, 6, 10 and 15 months (500 mg/m2 (maximum 1000 mg) and the patients were followed for no less than three years. The participants assessed their symptom levels every two weeks and health related quality of life using the SF-36 form.

Lymphocyte subpopulations, including CD19 positive B-cells were assessed before the infusions and at 3, 6, 10, 15, 20, 24, 30 and 36 months.

In an attempt to boost their response seven of the patients who showed slow and gradual improvement after twelve months received up to six additional infusions at two month intervals.

The Participants

This was Norway but the study population looked like that found anywhere else. Sixty-nine percent of the participants were women and 31% were men. The average age was forty and the average duration of illness was nine years. The severity of their illness ranged from mild (n=5), mild/moderate (n=4); moderate (mainly housebound) (n-13), moderate/severe (n=4), severe (bedridden) (n=3). Almost 60% associated an infection with their illness, 34% did not and 7% were not sure.

Seven patients had had Rituximab before but relapsed later and three had tried it and received no or a minimal response. Nine participants had been in the placebo arm of the former study.  All met both the Fukuda and Canadian Concensus Criteria for ME/CFS.

The Results

The Responders

As in the first trial over 60% of the participants reported significant clinical improvement; i.e. they achieved an improvement in their Fatigue score ≥ 4.5 for at least six consecutive weeks. Fourteen or 78% of those  who did were described as “major responders” and four (22%) were described as moderate responders.

more is better Rituximab

More was indeed better as many of the responders maintained their response a year and a half after receiving their last treatment

Some evidence suggested that the major responders were close to functioning normally or in some cases were fully recovered.  With their average SF-36 scores showing remarkable increases it appeared that many of the responders really responded. (More is better with the SF-36).

The average social functioning score – which denotes how much a person is inhibited from functioning socially – increased from 18.4 to 70.8, the average vitality score tripled from  17.7 to 61.3, the average physical functioning score – probably a really difficult one to improve on in ME/CFS – almost doubled (42.9 – 83.3), and bodily pain scores more than doubled (32.2 to 72.3).

At the end of the trial the responders average SF-36 score meet population norms; i.e. you wouldn’t be able, using this test, to tell them from healthy people. It didn’t mean they were all healthy- the test is not precise enough for that – but they were much, much improved.

Some limited Sensiware armband data validated the findings: the number of steps the responders took at the end of the trial indicated they were about as active as normal people.

The Non-Responders

The ten people who did not respond – really didn’t respond; no significant increases in any of the SF-36 scores were seen. It appears that most of the responders do pretty well while nothing much happens for the non-responders.

Maintaining Health – the Maintenance Strategy Mostly Works

The maintenance strategy of providing Rituximab more often to produce a longer-last effect was mostly successful.  Again, those who responded to it responded well. Those did not respond – really did not respond.

The duration of the response zoomed in the responders from 25 weeks (half a year) in the first study to almost 100 weeks (two years) when taking maintenance infusions in the second study.  The responders stayed healthier longer once they were off the drug as well. Three years after beginning the treatment and a year and a half after their last infusion  the treatment was sticking for about 60% of the responders. Some former patients were clearly well.

“Eleven of the 18 responders were still in remission three years after beginning the treatment, and some have now had no symptoms for five years,” Fluge.

B-cell tests indicating the B-cell numbers of all the responders were back to normal suggested their systems may have been reset. If they’d had an autoimmune problem it had disappeared during their long period of immune suppression.

The maintenance dose did not enhance the duration of the response in everyone, however; about forty percent had relapsed a year after receiving their last dose.

The More Is Not Better (Except When it Is) …..Group

Giving Rituximab more often (at the end of one year) to patients who’d had a moderate initial response to it failed to turn them into major responders.  One person, however, who didn’t respond to the two-dose first trial, did respond to five dose second trail.

More doses of Rituximab early on, then, might help but if a year of increased dosage is not helping then it’s time to try something else. Why some people respond and others don’t isn’t clear. Sophisticated immune analyses, however, are underway to attempt to figure that out.

Concerns

Placebo Response

There’s concern about the lack of a placebo group. No treatment will ever get approval without having a placebo controlled study but I wonder how serious the placebo concern is. The long time to the response seen (several months) and the long duration of the response argue (a year and a half in some) argues against a placebo response making a difference for many.

Study Size

A bigger concern is probably the small study size.  Thus far we have  response data on a small slice of the ME/CFS population in an ethnically homogeneous region.  (The upside to doing the study in Norway is that they can apparently get things done pretty quickly; the downside is that the country simply doesn’t have the ethnic diversity the U.S. has.)

subset

The biggest questions facing the two studies done so far is how closely the study participants resemble the ME/CFS population as a whole.

We can say that Rituximab works well  and sometimes very, very well in a subset of patients but we don’t know how big that subset is. I expect the response rates to drop as more types of ME/CFS patients sample the drug. Even a thirty or twenty percent response rate would be very exciting.

The results from the multicenter trial will not be available until 2017 or 18 – two or three years. If the 152 person trial goes well it’s hard to imagine – at least from this layman – that large trials will not quickly open up in the U.S. The infrastructure and the network of physicians needed to engage in a major trial is present. They will simply need access to the drug.  With all the federal reports citing the need for better treatments a way has to be found to get the” big lug” to mount a major trial.

The Severely Ill Study

Thus far in a separate study none of the four severely ill ME/CFS patients in a small open-label study have responded to Rituximab. Four more patients are being assessed. They do not encourage the use of this very strong drug in the severely ill at this time.

The Autoimmune Question – If it Looks Like A Duck…

Chronic fatigue syndrome with it’s female predominance, it’s often infectious trigger, it’s symptoms and the changes that sometimes occur in pregnancy has always looked like it might be, at least in part, an autoimmune disorder.

Fluge and Mella’s autoimmune hypothesis ties several aspects of ME/CFS together in a neat package. First an infection triggers the body to produce antibodies that target the blood vessels and stop them from delivering normal amounts of blood to the tissues. The drop in oxygen to the mitochondria resulting from explains the fatigue, lowered aerobic capacity and exercise problems. Given the brain’s enormous need for oxygen it also explain the brain fog. Several studies back up the muscle and brain issues – the question is whether antibodies are the result.

duck autoimmunity ME/CFS

If it looks like a duck and walks like a duck… is it a duck?

Thus far the Rituximab findings suggest autoantibodies play a role at least in a subset of patients. As before the responders took their sweet time – several months – to respond to the drug.  That several month time lag, though, is about how long it would take Rituximab to clear auto-antibodies from the body. That time-lag strongly suggests an autoimmune process is going on.

Increased rates of autoimmunity (41%) in the first-degree relatives of the patients buttressed the autoimmune hypothesis; a genetic predisposition is often present in autoimmune disorders.

If auto-antibodies are the key Fluge and Mella and others, however, have not found them yet.  They do have a hypothesis, though that ties several aspects of ME/CFS together in a neat package. They believe an infection triggers the body to produce antibodies that target the blood vessels and stop them from delivering normal amounts of blood to the tissues. The drop in oxygen to the mitochondria resulting from the reduced blood flows explains the fatigue, lowered aerobic capacity and exercise problems. Given the brain’s enormous need for oxygen it also explains the brain fog. it’s a theory with a nice foundation: several studies back up

We should see a paper explaining Fluge/Mella’s hypothesis soon and studies embedded in the 150 person trial will help assess whether their hypothesis is correct.

Norway!

It’s worth noting again what a remarkable role the small country of Norway has played in this unlikely scenario.  Size doesn’t always matter – and one suspects that it may be a hindrance in some cases. Two Norwegian physicians birthed the Rituximab findings, Norwegian advocates raised money and pressured the Norwegian government to do what nobody else has been able to do – fund and produce a very expensive and large treatment trial.  Not only did they do that but they did much more quickly than anyone else.

It’s a scary thing to have to depend on a small country with almost no history of ME/CFS research or on private donors in another country to follow up on the most exciting treatment finding in ME/CFS’s history.  If Rituximab works out – and it’s hard to imagine that it will not at least in part work out – the worldwide ME/CFS community will owe the two doctors, the Norwegian advocates and the Norwegian government a huge debt.

The UK is on board. It may be that UK advocates – driven by their awful circumstances – try harder when it comes to jumping on a hot treatment finding. Since June, 2013 Invest in ME has raised over $600,000 US dollars for its own Rituximab trial. According to Dr. Jonathan Edwards, who pioneered Rituximab’s use in autoimmune disorders, Invest in ME has enough money now for a small trial involving 30-40 patients.

That’s great and Norway  has already produced a much larger study and is years ahead of everyone.  That quick start is important given how long these treatment trials take and how long it can take to get approval for a drug.

A Rituximab Timeline

Let’s look at a Rituximab timeline. Fluge and Mella identified their first Rituximab responsive ME/CFS patient in 2004. Their three person case study was published in 2009.  Their 30 person placebo-controlled study was published in Oct. 2011. They began the 152 person multicenter trial at the end, if I remember correctly, of 2014. That study should end in late 2016/early 2017. It will take some time to analyze the results and then get them published. Perhaps we’ll see a paper in early 2018.

You can argue that moving from a small case-study in 2009 to a large multi-center trial beginning in 2014 is good progress and it probably is, but it’s still five years in the life of an ME/CFS patient.

The Big Lug

Much of the innovative research, both inside and outside the public sphere, is occurring in the U.S. but the Rituximab trials might never have happened for all the work that’s been done here. That’s something that ought to give one pause.  A possible new treatment for a disorder with no FDA-approved drugs occurs and the biggest and richest country in the world does nothing.

head in sand

The country with the biggest medical system in the world hasn’t figured in the Rituximab story at all yet

How does that happen? Norway got funding from both advocates and the government. UK advocates have raised $600,000 by themselves. No group has mounted a serious effort in the U.S. and federal funding for clinical trials is difficult to achieve.

It’s pretty clear right now that nothing’s going to happen around Rituximab in the U.S. until the Norwegian trial ends up in mid 2017. Say the Norwegian results published in 2018 are impressive and the U.S. gets a major year-long trial started in early 2019.  The results are in by mid-2020, they’re submitted for publication in early 2021, are published in mid-2021. The FDA examines the data from the US, Norwegian and UK trials and in early 2022 seven years from now, approves Rituximab for use in a subset of ME/CFS patients.

When U.S. – because of bureaucratic or institutional barriers or whatever, is simply sitting on the its hands everything takes longer. In another disorder the Oct 2011 Fluge/Mella study might have sparked an extensive U.S. treatment trial in 2012.  The first results of that multi-year trial might have been published in say 2015.  In this scenario with the big Norwegian study underway we’d have enough data to apply for FDA approval in two years.

An Unlikely Ally

The two studies have created an unlikely ally. Simon Wessely – the foremost proponent of the idea that ME/CFS is caused by poor coping and deconditioning – has been impressed enough by the results to call for a large trial. “There is now a strong case” he said  “to be made for a larger trial”.  Whatever you think of Wessely that’s a very helpful statement coming from a man of his background.

The silver in the lining of the United Kingdom’s embrace of CBT/GET is the extent to which they’ve funded it. The UK, per capita, has been far more generous with ME/CFS funding than the U.S. and they’ve shown the willingness to put significant dollars (or pounds) behind a treatment trial. Drug trials in the U.S., on the other hand, appear to be almost solely funded by pharmaceutical companies. Wessely – recently knighted – has a lot of pull in the U.K.  Could Wessely prod the UK government to get behind an enlarged Invest in ME Rituximab study? That would a be flip of major proportions.

Wessely also said “The belief that [CFS] is all in the mind has been around since the beginning,” he says. “It’s tragic that it might take a study like this to take sufferers seriously.” That’s quite a statement given his history. Check out how that statement jives with Wessely’s past ones in Simon Wessely’s Big Shift? CBT Icon Calls For Big Rituximab Trial

Conclusions

It was a remarkable thing to see almost half the study population exhibiting normal or near normal SF-36 and activity scores after three years.  Even if this is a small study the almost identical response rates (a strong 60 plus percent) found in it and the first study  are encouraging.

This study also demonstrated that give doses more often eliminates many of the relapses that dogged the patients in the first study and it presented more evidence that this powerful drug  is generally safe for use in ME/CFS patients.

As promising as the results of the first two studies are it should be noted that they are small studies and surprises may show up in the larger study underway. It is using the same improved treatment protocol used in this study. It’s results will probably not be published for several years.

In the meantime, this study prompted a major CBT advocate to call for larger studies and a smaller UK trial is in the process of being produced. (You can support that study here.)

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36 Comments

  • Chris Williams

    July 6, 2015 at 7:18 pm - Reply

    As a 63 year old patient who has been ill for nearly 7 years, the lengtly delay is distressing. I would like some improvement in my lifetime. I didn’t plan to spend my retirement on the sofa. The failure of the US Government to act is a travesty.

    • Kathy Olsen

      July 7, 2015 at 1:08 am - Reply

      Hi Chris, I’m 67 and I should be living my retirement now. But can’t, because I just sleep so much. At least I have my PC to what’s going on in the world. And I see this and oh so wish we could do it now. I would be gladly do a trial now. Or even just do it on my own with my Dr. Think that the USA would let us?

  • Rick Newlands

    July 6, 2015 at 7:34 pm - Reply

    As I describe in my book on M.E., my background in the Space industry showed me the similarities between M.E. and hypoxia/altitude sickness: a lack of oxygen, as Fluge and Mela hypothesise. The symptoms are identical.

    • Cort Johnson

      July 6, 2015 at 10:42 pm - Reply

      Do you have a URL for your book?

    • Funkyqueen

      July 7, 2015 at 3:27 pm - Reply

      I do not know what to think about the Fluge and Mella’s theory explaining poor oxygenation:
      I took non -stop for 3 months, every night during 6:00 / 6:15, medical O² at the rate of 1.5 L to 3.5 L per minute.
      No improvement.
      Meanwhile, another ME sufferer I know has a major response to oxygen therapy, but he has a fall of O² revealed by his polysomnography, whereas I do not. Yet we are well severe PWME both. I post-viral form, and he, post -vaccinale form.

      • Cort Johnson

        July 7, 2015 at 3:33 pm - Reply

        I wonder if even then – if your small blood vessels are to some degree blocked off – if it’s not all getting through (???)

      • tim

        July 8, 2015 at 9:44 am - Reply

        Dr. Cheney regards O2 as toxic to CFS patients, because he sees that it decreases heart function.

        • Prashanti

          July 9, 2015 at 3:43 am - Reply

          This is quite interesting to me. I began to, on my own, measure my BP, blood glucose, and O2 . I do usually have low O2. I have even been tested to need ioxygen at night when sleeping.
          I hadn’t thought about this being related to CFS. However I do get a sense that there is not enought O2 going to the brain.
          I’d like to find out more about who Dr. Cheney is and why he feels more O2 is toxic for CFS.

          • tim

            July 9, 2015 at 6:17 pm -

            Google Cheney and oxygen toxicity, you will find it.

  • MareeC

    July 6, 2015 at 9:51 pm - Reply

    The NIH is currently funding a Phase 2 rituximab trial for myasthenia gravis patients. Myasthenia gravis is an autoimmune illness affecting around 20 people in 100,000.

    The parties involved in the Myasthenia gravis trial are NIH’s National Institute of Neurological Disorders and Stroke (and NeuroNEXT, it’s neurological research network); Yale University; and Genentech Pharmaceuticals who is providing the rituximab). See http://www.neuronext.org/nn103-rituximab-mg.

    ME/CFS is estimated to affect at least 200 people per 100,000, ten times that of Myasthenia gravis. The US government has an urgent need to show some real action on ME/CFS following the IOM and P2P reports.

    I think patient advocates in the US should be knocking of the door of NIH, the National Institute of neurological disorders and stroke, Yale University (Richard Nowak) and especially Genentech, armed with the Fluge and Mella results and strongly suggesting that a rituximab trial for ME/CFS would be relatively easy to do and would meet with enormous patient approval.

    I note that the summary for the Myasthenia trial says “this work will further our understanding of MG immunopathology and it represents the first step toward gaining a more complete understanding of the immune mechanism underlying treatments of MG with rituximab leading to new ways to treat the disease”. This is exactly what is needed for ME/CFS.

    • Cort Johnson

      July 6, 2015 at 10:41 pm - Reply

      Very interesting. It looks like Genentech is providing the drug and NeuroNext is backing it and Yale is sponsoring it.

      NeuroNext is a NINDS initiative to conduct exploratory trials in neurological conditions. It receives proposals from academics, foundations and industry. All proposals are evaluated for mission relevance and institute priority by NINDS and for network feasibility by the NeuroNEXT Executive Committee (NEC).

      We really should be in NINDS I believe. If we were in NINDS we would have access to that group….

      From what I’ve been told overtures have been made by some parties to Genetech. It appears they have not been successful thus far – but here we have another positive study…

      I wish Fluge and Mella could release their trial results after a year on the drug. I don’t know who feasible that would be but that would save a year I believe. This is taking sooo long.

      Very interesting. I had no idea a study like that was going on.

  • MareeC

    July 6, 2015 at 9:54 pm - Reply

    Cort, sorry, that comment looked ok in the little submission box. But I see it is missing spaces between paragraphs here. Could you please edit it to add those spaces for me? Thanks

  • MareeC

    July 6, 2015 at 10:51 pm - Reply

    Cort, thanks for fixing the format of my comment.

  • William

    July 6, 2015 at 11:22 pm - Reply

    There are 412 clinical studies involving rituximab currently recruiting. See the list https://clinicaltrials.gov/ct2/results?term=rituximab&recr=Recruiting&pg=1.
    There are 2 studies underway for Chronic Fatigue Syndrome/ME. See them https://clinicaltrials.gov/ct2/results?term=rituximab&recr=Recruiting&rslt=&type=&cond=chronic+fatigue+syndrome&intr=&titles=&outc=&spons=&lead=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s=&lup_e=.
    I couldn’t see any for Fibromyalgia.
    If you have another medical condition(s) you may add it/them to the search results and see if there are any studies specific to it/them.

    • Cort Johnson

      July 6, 2015 at 11:25 pm - Reply

      Thanks William. Rituximab is amazingly well studied! You’d think we could sneak a trial in there! 🙂

  • Monica Bolton

    July 7, 2015 at 11:23 am - Reply

    Cort – you show just how long it’s going to be before rituximab is likely to get a license in ME/CFS. But some people do respond to other drugs – not as well usually but well enough to make a difference to their life. I think we should use these results to point out the need for more clinical trials of other drugs (ampligen, LDN, SSRIs, antivirals etc) which, because they are cheaper or better known, could get licensed quicker. The experience of organising trials in these drugs would also help researchers in the long run. It’s no accident that the rituximab trials were organised by haematologists, and organised very meticulously – clinical trials are part of the bread and butter life of haematologists because of co-operating in clinical trials of leukaemia and lymphoma treatments.

    • Cort Johnson

      July 7, 2015 at 1:36 pm - Reply

      I just have a guess and who knows what the future will bring. My guess is that it will take 5-7 years if things go well. Perhaps something could pop up which would shorten that process. We would probably need two large studies to get it approved.

      Ampligen is another good candidate but Hemispherx doesn’t have the funding to do a large trial and probably can’t get funding to do one.

      There is the two-drug combo SolveME/CFS is trying to get funding for a trial for. That, the Synergy product and the Pridgen antiviral trial for FM might be the quickest routes to FDA approval.

  • Lois d'Annunzio

    July 7, 2015 at 3:13 pm - Reply

    If Rituxam is approved for cancer & R.A. and is being used off label for other autoimmune diseases, I don’t see why it couldn’t legally be used off label for CFS. Frankly, I can’t wait 7 yrs. for approval. Although,I don’t know of a doctor who would administrate it. I am so sick of living my %$@%^ life through TV and stories from friends about all their travels and adventures. I want a life now. Seems like the FDA should, at least, fast track this drug.

    • Cort Johnson

      July 7, 2015 at 3:34 pm - Reply

      It can be – and some doctors do it – but they’re rare. I’m not sure how they do it – they probably need some signs of immune dysfunction (high ANA levels??) – to justify it. From what I hear it’s a very expensive drug with possibly significant side-effects (which admittedly, have not shown up yet.)

  • Lois d'Annunzio

    July 7, 2015 at 3:59 pm - Reply

    I didn’t mean to shoot the messenger but I feel that having no treatment available is a violation of the Bill of Rights.”Pursuit of “Life, Liberty and the pursuit of Happiness”

    I’m just tired of our government mistreating CFS patients, probably because they see it as “girlie” thing. Which is discrimination. To bad I’m not a lawyer.

    Sorry for my rant, Cort, because when I see a post from you it always gives me hope.

  • Lois d'Annunzio

    July 7, 2015 at 4:09 pm - Reply

    I didn’t mean to shot the messenger. Every post in my in box from you gives me hope.

    However, I feel this terrible treatment from our government is in violation of the Bill of Rights. “Life, Liberty and the pursuit of Happiness”

    I also believe that the FDA has done nothing is partly because they still see this a disease is for ‘”rich, lazy, whiney women”.
    Another violation of anti discrimination laws. Should have been a lawyer. Done

  • Firestormm

    July 7, 2015 at 7:20 pm - Reply

    Hi Cort,

    I thought Kogelnik was doing a trial of Rituximab or at least planning one? But have heard no updates other than from people who he has seen as private patients – reporting in the main that they haven’t responded.

    Is it possible that Kogelnik is not seeing the same kind of results in his patients as the Norwegians have reported and he is no longer proceeding because of this? Or perhaps he and the Foundation are now focusing on their Severe study instead?

    I know the Germans were waiting on Norway’s Phase III results, and I would imagine that perhaps others are as well. There has been no start-date issued for the proposed UK trial – though I don’t understand why they haven’t started on it – but the study UCL in London is currently working on financed by Invest in ME does look interesting and important.

    What we need are multi-centre trials in the UK and Europe and USA. BIG ONES. And financed in the UK by Medical Research Council and non-profits working in collaboration. Else despite what Norway might produce and even with a small trial from UCL – we don’t stand a great chance of gaining approval of this drug in the UK especially for something like ME/CFS despite perhaps Wessely’s latest – albeit welcome – musings on Twitter.

    • Cort Johnson

      July 8, 2015 at 12:01 pm - Reply

      I’m in touch with Kogelnik. Have asked him some questions about Rituximab. It’ll take some time for him to get back to me. I think the OMF is focusing on the severely ill study.

  • Sonja Steyn

    July 8, 2015 at 5:11 pm - Reply

    I am one of the few ones that survived cfs for 27 years , with the Rituximab study its the first time I feel a glimmer of hope , but if we in the Usa have to wait 7 years, I sincerely hope by the mercy of God I will be out of this body very soon.

  • Kim & Kelly Derrick

    July 8, 2015 at 8:02 pm - Reply

    I am 60 and my sister is 46, but we’ve had CFS since we were babies. Waiting another 5-7 years is just plain vicious.

    There is another aspect to this topic that no one seems to have touched on. The adverse effects of rituximab (as with all the -mabs) are pretty harrowing.

    Serious adverse events, which can cause death and disability, include:[34]
    -Severe infusion reaction.
    -Cardiac arrest
    -Cytokine release syndrome
    -Tumor lysis syndrome, causing acute renal failure
    -Infections:
    -Hepatitis B reactivation
    -Other viral infections
    -Progressive multifocal leukoencephalopathy (PML)
    caused by activation of JC virus
    -Immune toxicity, with depletion of B cells in 70% to 80% of lymphoma patients
    -Pulmonary toxicity[35]
    -Bowel obstruction and perforation[36]
    Patients have died [37]
    (See source citation below)

    These problems occur in a small percentage of patients, but that doesn’t help those people, especially the dead ones. We both have had bad reactions to a number of medications, so the adverse list for rituximab is daunting to say the least.

    There are other medications with massively fewer, less drastic adverse effects like antivirals, steroids, isocoritsol, interferon, oxymatrine (also in Equilibrant), and seanol (also in FibroBoost). We’ve had some results in the past with the antiviral acyclovir, but haven’t found a doctor that will prescribe it now. We had good results in the past with interferon, but haven’t found a doctor that will prescribe it now. I’ve had some good results in the past with prednisolone, but haven’t found a doctor that will prescribe it now. I’m having some results with
    oxymatrine and seanol, but I’ve started slowly exceeding the recommended dosage because I need a lot more help than the standard dosage provides. (I can’t take Equilibrant because the licorice extract and astragalus extract elevate my blood pressure.) We discovered the isocortisol by accident and the FDA has since taken it off the market. They “protected” me right back into bed. (I just sent an email to Dane Cooke, PhD telling him about our success with isocortisol. I suppose the waiting period on that would be 10+ years.)

    There are medications out there. We just haven’t been able to find a doctor that would prescribe them. (I’ve been on Dr. Bateman’s waiting list for 2+ years.)
    _______________
    (Adverse Reaction Sources: Wikipedia, Rituximab
    https://en.wikipedia.org/wiki/Rituximab
    Footnote sources:
    34. “Genentech: Products – Product Information – Immunology – Rituxan RA Full Prescribing Information”. Retrieved 2007-12-03.
    http://www.gene.com/gene/products/information/immunological/rituxan/insert.jsp
    35. Burton C, Kaczmarski R, Jan-Mohamed R (2003). “Interstitial pneumonitis related to rituximab therapy”. N Engl J Med 348 (26): 2690–1; discussion 2690–1. doi:10.1056/NEJM200306263482619. PMID 12826649.
    https://dx.doi.org/10.1056%2FNEJM200306263482619
    36. “Reports of Bowel Obstruction and Perforation with RITUXAN (rituximab)” (PDF). Roche Canada. 2006-11-10.
    http://rochecanada.com/portal/servlet/staticfilesServlet?type=data&communityId=re753001&id=static/attachedfile/re7300002/re77300002/AttachedFile_04801.pdf)
    37. “Rituximab (marketed as Rituxan) Information”. Retrieved 15 November 2009.
    http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109106.htm

    • Cort Johnson

      July 8, 2015 at 10:05 pm - Reply

      These side effect sheets can be so daunting but I am struck by the fact that Fluge/Mella have treated a good number of patients without having any serious side effects. The same appears to be true with some antivirals that ME/CFS patients often do quite well on. I must conclude that not many people get them – thank goodness.

  • Guido den Broeder

    July 12, 2015 at 9:07 pm - Reply

    The patients that respond are the ME patients. It’s that simple.

  • Deborah Waroff

    July 12, 2015 at 11:52 pm - Reply

    I am greatly saddened by Kim and Kelly Derrick’s inability to obtain prescriptions for commonly used drugs that can be legally prescribed to them off-label. Clearly doctors are frightened, as well they might be. The persecution of the chronic Lyme doctors in Connecticut and New York and the persecution of Dr. Shoemaker in Maryland have made clear the potential losses to doctors from trying too hard to help their patients. There have been persecutions of ME doctors as well; our doctors are easy to persecutive because CDC only approved CBT and GET as treatments, and now not even those measures exist on the record, because recommendations were archived pending change a few months ago.
    Indeed, one recalls that a few years back one very prominent ME doc was so intimidated by the persecution apparent when a colleague was prosecuted for trying to treat ME outside CDC guidelines (our doctor had been called as a witness in the case) that she feared even to disclose the jurisdiction or any details of the case.
    The multiplication of regulations over medical care in recent years, including the provisions of Obamacare, have enhanced the variety of grounds on which ME doctors can be prosecuted. Or persecuted. Also, increased entrenchment and enrichment of insurers under Obamacare may increase difficulty of gaining reimbursement for off-label prescriptions if, indeed, one can obtain such, which difficulty the Derricks attest to.
    We are where we are because important and powerful people in key positions hate us, as Hillary Johnson and others have documented. Like the Derricks, I have lost most of my adult life to ME because important and powerful people hate us.
    Despite the obstacles of traveling with ME, just nine days ago I was in Poland, sitting under bright sun alongside the smartly restored barracks of the vast Nazi-built concentration camp, work camp and death camp complex that was Auschwitz. There 60 companies ran prospering factories that exploited slave labour of Slavs and those Jews spared death for the moment, while at adjacent Birkenau trainloads of Jews from all over Europe were being efficiently sorted, induced to strip naked, and beguiled to walk quietly into gas chambers to die.
    I learned a new bit of history that day. Near the end of the war, as the Nazis realized they were losing, Himmler ordered that all camps stop slaughter. Adolf Eichmann, however, could not bring himself to stop killing Jews. He disobeyed headquarters, and had Auschwitz-Birkenau carry on murdering innocent children, women and men until the Red Army arrived. It reminded me of some Federal bureaucrats, once called upon to save Tahoe from panic, who just can’t seem to stop hating us.

    • Cort Johnson

      July 15, 2015 at 5:57 pm - Reply

      Comparing federal officials to Naz’s is honestly not going to help and is simply not accurate. Yes, ME/CFS patients and doctors are not getting the support they need, and yes, some doctors using alternative methods are getting investigated by the FDA. They have always had this problem whether they treated people with ME/CFS or not. Nobody with ME/CFS is getting hunted down and thrown into concentration camps or put into ovens because they have ME/CFS. I understand the anger but I would use a less provocative analogy. That kind of analogy is so upsetting that it turns off discussion…

      ME/CFS has the same problem that FM, IBS, migraine and other predominantly women’s disorder that cause pain and disability but don’t kill have – the NIH is just not interested. They’re not interested in working on them. They’re mostly interested in studying in clean, clearcut diseases that kill people. Everything else is mostly foo-foo to them. Its not that they hate us – why would they hate us? why would they hate a disease? They have different priorities and feel they have better things to do…

      This really “criminal neglect” of millions of people is very upsetting situation – but calling them Nazi’s or using Nazi’s to refer to them gives them a way to marginalize further in my opinion

  • Johannes

    July 13, 2015 at 8:16 am - Reply

    Very exciting development with Rituximab! Thanks for this great write up.

  • Anne Ö

    July 15, 2015 at 12:16 pm - Reply

    I look forward to hearing where Kogelnik’s at!

    But Cort, I think Simon Wessely “prodding the government” to get behind a large UK Rituximab study is….. somewhat unrealistic, to be British about it. Completely crazy, in more American words… The man is trying to save his skin now that history is about to turn against him by going on record saying some non-committal stuff – he’s been obstructing all progress in the ME field for decades, there is absolutely no way he’s suddenly going to help us get biomedical trials!

    • Cort Johnson

      July 15, 2015 at 5:45 pm - Reply

      I was in a clearly over optimistic state when I wrote that….:). Still it’s good to have Wessely, of all people. saying that.

  • McGregor

    July 23, 2015 at 9:14 pm - Reply

    I am a 61 year old male and I have suffered from chronic fatigue syndrome at least since age 6.I did have a massive urinary tract infection at that time but which went undiagnosed until complete renal failure at age 12 in 1966. That may have been the cause or perhaps one of the many other infections and illnesses I suffered concurrently with the urinary infection. Having never really recovered from those childhood illnesses I do not know what an ordinary life might have been like. I always did work arounds for virtually every aspect of my life. I was not a failure because I always assumed “it was all in my head” or that “I was just lazy and the illness was an excuse to not work harder” or “I was just not a very strong person” or worse yet ” You are just a failure and are just like your father” He had died when I was only 7 so I hardly knew him but the heritable implications were clear. Thi was from my Mother of course. I worked ten times as hard as anyone I knew just to stay afloat and to compete in the world at an average level of activity and competence. Thousands of times I wondered what is wrong with me? What have I done to deserve this pain , this hideous sickening pain upon the smallest of exertions? I had a thousand reasons thought up as to why and what was wrong. About 10 years ago my physician and I came to the conclusion that I had chronic fatigue / myalgic encephalomyelitis. I was only formally diagnosed just 2 years ago by a different physician. I was awarded disability 2 years ago as well but not for the CFS/ME but for concurrent issues of a badly deteriorated spine and knees as well as COPD. Isn’t it a fine thing to live in the most powerful nation on earth but to have led a life as I have because our medical expertise (in CFS/ME) is essentially zero and our medical delivery system is primarily designed only to serve the well insured and the wealthy. We can afford near continuous foreign war but a national health care system is out of the question, far too expensive.

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