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Mabthera/rituximab from India/Israel

redo

Senior Member
Messages
874
It seems like perispinal enbrel injection might work better and quicker (thanks for the links). Perhaps perispinal might work if SC injection doesn't. The most common response pattern for SC use is a little longer, weeks to months.

Mella/Fluge writes some interesting paragraphs about it: "An alternative for patients with typical CFS / ME illness strict diagnostic criteria, but no response after Rituximab, the use of a TNF inhibitor Enbrel. In autoimmune diseases like arthritis seen the effects of illness often after a few weeks, as this is mediated via the elimination of the cytokine directly". (nice to see their opinion is that cytokines reactions might be central in generating the symptoms)
(...)
There are no published scientific published study that evaluated the use of Enbrel in CFS / ME. However, there is a contemporaneously where six CFS / ME patients had been treated with etanercept with good clinical effect, but these results have not been published later (Lamprecht K. American Association of Chronic Fatigue Syndrome, Seattle 2001). In addition, individual patient unpublished stories available (link).

Kristin says the following about Enbrel: "I was in a “pre-study” with Enbrel back in 2000. I have CFS-moderate. For the first weeks-nothing. Week 5-8 I felt wonderful. Not completely normal, but SO much better. I cried when I had to stop at 8 weeks and found out the cost of Enbrel. What I would not give to see Enbrel further studied and approved for CFS treatment. (link)"

I am actually trying to get on it now. If you'd like I could PM you with info on how it goes. I barely write about these things in public, since I really don't want attention to it - even though the web is anonymous. By the way, I really like your approach with thinking out load. I think tossing ideas back and forth are key to moving forward. The more knowledge one gets about mechanisms, the less fumbling in the blind it becomes.

Although I wouldn't recommend to anyone else taking RTX or equivalents, it seems like India is a better alternative than Spain if getting it at a hospital at a reasonable price is the objective. When dispensing RTX, they need an ER at the hospital, just in case - but it's rare that it's actually needed. It's standard procedure to give cortisol just before the RTX to minimize such risks. Dr. Reddy's Laboratories being a publicly traded company, is reassuring.
 

Jacque

Senior Member
Messages
424
Location
USA - California
Where did you get this number. It seems awfully high. Do you have the gene for Alzheimers as some forms are genetic.

Thanks.
Barb C.
I believe I heard a talk by the doc at Florida Detox and Wellness center in Florida... I you google that you will find the site... Can't remember his name.. He has a lot of great talks on his site... And come to think of it it was not on one of the recorded talks he does it was on one of his conference calls and I remember being BLOWN AWAY by what he said and took many notes from the call. That does seem quite high...but with the baby boomers aging and saturation occuring...I guess it is possible. I will see if I can dig up the notes...it was over a year ago... He has GREAT conference calls about the Brain, drugs, etc... even Lyme!!

I am adopted so I don't know...and haven't been tested...what is the gene they test for do you know??? Do we want to know??? ugh
 

Jacque

Senior Member
Messages
424
Location
USA - California
It seems like perispinal enbrel injection might work better and quicker (thanks for the links). Perhaps perispinal might work if SC injection doesn't. The most common response pattern for SC use is a little longer, weeks to months.

Mella/Fluge writes some interesting paragraphs about it: "An alternative for patients with typical CFS / ME illness strict diagnostic criteria, but no response after Rituximab, the use of a TNF inhibitor Enbrel. In autoimmune diseases like arthritis seen the effects of illness often after a few weeks, as this is mediated via the elimination of the cytokine directly". (nice to see their opinion is that cytokines reactions might be central in generating the symptoms)
(...)
There are no published scientific published study that evaluated the use of Enbrel in CFS / ME. However, there is a contemporaneously where six CFS / ME patients had been treated with etanercept with good clinical effect, but these results have not been published later (Lamprecht K. American Association of Chronic Fatigue Syndrome, Seattle 2001). In addition, individual patient unpublished stories available (link).

Kristin says the following about Enbrel: "I was in a “pre-study” with Enbrel back in 2000. I have CFS-moderate. For the first weeks-nothing. Week 5-8 I felt wonderful. Not completely normal, but SO much better. I cried when I had to stop at 8 weeks and found out the cost of Enbrel. What I would not give to see Enbrel further studied and approved for CFS treatment. (link)"

I am actually trying to get on it now. If you'd like I could PM you with info on how it goes. I barely write about these things in public, since I really don't want attention to it - even though the web is anonymous. By the way, I really like your approach with thinking out load. I think tossing ideas back and forth are key to moving forward. The more knowledge one gets about mechanisms, the less fumbling in the blind it becomes.

Although I wouldn't recommend to anyone else taking RTX or equivalents, it seems like India is a better alternative than Spain if getting it at a hospital at a reasonable price is the objective. When dispensing RTX, they need an ER at the hospital, just in case - but it's rare that it's actually needed. It's standard procedure to give cortisol just before the RTX to minimize such risks. Dr. Reddy's Laboratories being a publicly traded company, is reassuring.

I sooo hope you are able to get the Enbrel again..and I really want to hear how you do on... If the Ritux does not do the job on my pain levels that may be something for me to try in the future...Always gotta keep HOPE in the pipeline and a back up plan... Jac
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
Thanks, Redo. I do make a point of avoiding threads where people seem to want to somehow "win" debate, it's better to bounce ideas and hopefully arrive at knowledge that might be useful. I chose the name 'Sherlock' not to say that I have answers but because I think that proceeding logically is the best approach for me, rather than seeking experts. Since we're all here, we can all share the research load and post excerpts that save time for others.

Speaking of which, your quote from the Norwegians is very interesting because up until reading that I'd assumed they were only pushing the autoantibody explanation. That requires the pre-existing autoantibodies and the plasma cells producing them to disappear over a timeframe that likely takes months. Jacque's fast response reported here on PR is the opposite - pointing at altered signalling instead.

I kind of make a joke to myself about 'homemade rituximab' but it seems conceivable in a way: not to kill the B Cells but instead to mimic what happens regarding signalling - even using OTC means. EGCG from green tea extract comes to mind immediately, though large doses might lower testosterone. EGCG is cytotoxic in large doses, but also is being looked at as inhibiting B Cell signalling in lymphoma. Even so, I assume that's much weaker than real drugs.

Yes, kindly let me know via PM about your Enbrel experiences. Btw, one can apparently order Reditux and have it shipped anywhere, including to the U.S., for now. Send PM if you'd like info.


I have seen lots of RTX given in the 'infusion centers' at private practices here in the U.S. Yes, MDs (oncologists/hematologists) are present, of course. It's a big money maker and AFAIK cheaper than at a hospital. Btw, it's not quite cortisol that's given but Solumedrol, i.e., IV methylprednisolone - but that's pretty much the same thing. With IV diphenhydramine and Tylenol.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
Is there any publically available safety data on the various biosimilar drugs? Reditux for example?

I've discovered that although all of these drugs target the same glycosylated phosphoprotein, when the drug is produced with a different method, it will necessarily be different in structure/phosphorylation and so this is why new safety trials have to be done to prove that the biosimilar drug is safe.

Hi, Snow Leopard. Here's a masters thesis from 2010 on the whole subject, by Student name (Carlos) Kuo-Hsuan Liang
http://igitur-archive.library.uu.nl/student-theses/2010-1112-200315/thesis_biosimilar.pdf

It says there is none available.
As the first wave of biosimilar mAbs, Reditux (a biosimilar rituximab developed by Dr. Reddy) and Clotinab (a biosimilar abciximab developed by ISU ABXIS) have been launched respectively in India and in South Korea.[49]
Although no further information available to show how these biosimilar mAbs are comparable to the reference products, or whether they are under the pathways as rigorous as EU’s regulatory framework...


I'm going to go out on a limb and guess that the maker says that Reditux is great and the patent holders and competitors says that it is unproven and risky. :)

http://www.drreddys.com/products/popups/reditux.htm

There was also an open forum with a panel comprising the clinical trial investigators and the members of the independent Data Safety Monitoring Board
I didn't know they done had a trial. I don't see data available.

Here is something from WHO:
Using the example of Reditux (Shantha Biotech, India) which has the same amino acid sequence as the originator, Rituxan (anti-CD20 monoclonal antibody, Hoffman La Roche, Switzerland), he highlighted many differences at the quality level between the two products which clearly demonstrated that Reditux is not a biosimilar of Rituxan and may therefore have a very different safety and efficacy profile.

I suppose Shantha is the actual developer, as Biogen Idec is with Genentc's Rituxan. I don't know if something coming from the W.H.O. gives greater credibility or just a greater chance of bribery.


Here is something that talks about greater efficacy, in a very small trial: http://www.britcham.com.br/download/211010_Dr_Morton_Aaron_Scheinberg_HAE.pdf The chintzy server is broken, I can't get to it now.


The thesis by Liang cited above mentions an interesting point: if the copy drug is actually better than the original (say in half life or purity), then it doesn't qualify as a biosimilar.
 

Hip

Senior Member
Messages
17,824
I enquired for Reditux pricing: ~$700 Yankee dollars for 500mg.

So it seems that Reditux from India costing around US$ 700 for 500 mg is half the price of Rituxan costing US$ 1,400 for the same amount. (This document quotes UK£873 = ~US$1,400 for one 500 mg vial of rituximab).

Plus of course the hospital bills are presumably going to be much cheaper in India. Anyone got any approximate figures for the hospital costs for administering Reditux to a patient in an Indian hospital?

I also understand that hospitals in Thailand are very clean, modern and cheap, so if they offered Reditux there, that might be another destination worth considering.

The Øystein Fluge and Olav Mella paper says that an infusion dose of rituximab at 500 mg per meter squared of body surface area was given to ME/CFS patients twice, two weeks apart. The body surface area for a person of average height and weight around 80 kg (176 pounds) is around 2 meters squared, so this means that by Fluge/Mella's protocols, you get a dose of 1000 mg Rituxan at each infusion.

So these two infusion doses would mount up to 2000 mg, and cost a total of US$ 2,800 if you used Reditux from India, or around US$5,600 if you used Rituxan.

If you then needed to repeat this same dosing protocol say two times a year, your total yearly treatment costs would be US$ 5,600 if you used Reditux from India, or around US$11,200 if you used Rituxan, excluding doctors' and hospital bills.


Anyone think it might be a good idea to set up an ME/CFS patients' residence or commune in say Thailand or India? All that health-promoting sunshine and good weather, plus in addition to your ME/CFS cure, you might even spend some time following your spiritual pursuits, if you are so inclined, as a sort of total body, mind and spirit rejuvenation; or alternatively, with the increased health and energy you have, start some type of business there (such as a business running a residence or commune in Thailand or India for further ME/CFS patients that want to come over and get cured cheaply...).



EDIT: In India you can also get the same Rituxan/MabThera made by Roche, but under the Ristova or Ikgdar brand name (but still made by Roche), for around $600. See this thread.
 
Last edited:

Jacque

Senior Member
Messages
424
Location
USA - California
So it seems that Reditux from India costing around US$ 700 for 500 mg is half the price of Rituxan costing US$ 1,400 for the same amount. (This document quotes UK£873 = ~US$1,400 for one 500 mg vial of rituximab).

Plus of course the hospital bills are presumably going to be much cheaper in India. Anyone got any approximate figures for the hospital costs for administering Reditux to a patient in an Indian hospital?

I also understand that hospitals in Thailand are very clean, modern and cheap, so if they offered Reditux there, that might be another destination worth considering.

The Øystein Fluge and Olav Mella paper says that an infusion dose of rituximab at 500 mg per meter squared of body surface area was given to ME/CFS patients twice, two weeks apart. The body surface area for a person of average height and weight around 80 kg (176 pounds) is around 2 meters squared, so this means that by Fluge/Mella's protocols, you get a dose of 1000 mg Rituxan at each infusion.

So these two infusion doses would mount up to 2000 mg, and cost a total of US$ 2,800 if you used Reditux from India, or around US$5,600 if you used Rituxan.

If you then needed to repeat this same dosing protocol say two times a year, your total yearly treatment costs would be US$ 5,600 if you used Reditux from India, or around US$11,200 if you used Rituxan, excluding doctors' and hospital bills.


Anyone think it might be a good idea to set up an ME/CFS patients' residence or commune in say Thailand or India? All that health-promoting sunshine and good weather, plus in addition to your ME/CFS cure, you might even spend some time following your spiritual pursuits, if you are so inclined, as a sort of total body, mind and spirit rejuvenation; or alternatively, with the increased health and energy you have, start some type of business there (such as a business running a residence or commune in Thailand or India for further ME/CFS patients that want to come over and get cured cheaply...).
 

Jacque

Senior Member
Messages
424
Location
USA - California
Sounds like a WONDERFUL idea....but should we wait n see how this trial goes? I have had 2 infusions and I am in NO WAY at all cured.. Have 4 more to go.... Had a few weeks with more energy but then the flu symptoms came back and the pain has never improved from day one. But I still think you are thinking in the right direction...and the more we think about what we all want...the more we will all attract it!! :)
 

Hip

Senior Member
Messages
17,824
Sounds like a WONDERFUL idea....but should we wait n see how this trial goes? I have had 2 infusions and I am in NO WAY at all cured.. Have 4 more to go.... Had a few weeks with more energy but then the flu symptoms came back and the pain has never improved from day one. But I still think you are thinking in the right direction...and the more we think about what we all want...the more we will all attract it!! :)

Yes, I guess we should wait and see. I am definitely reading your posts with great interest, Jacque, and I hope that the recent return of your fatigue and symptoms is just a temporary blip on the path to much better health.

I guess I am thinking ahead a bit. But if rituximab does turn out to work for most people with ME/CFS, then we will need to think of good ways to make it easy to do and relatively affordable.

Anyway, I have always wanted to travel to and spend some time in Asia !

Do you know what mg dose of rituximab you are getting in each infusion, by the way? Is the dose around the 1000 mg mark that seems to be used in the Fluge/Mella study, or are you getting more or less than that? And is the time interval between the infusions you are getting also a couple of weeks like in the Fluge/Mella study? Or are your 6 infusions going to be stretched across a longer time, like a year or so? Just wondered what approach your doctors are taking.
 

Jacque

Senior Member
Messages
424
Location
USA - California
Yes, I guess we should wait and see. I am definitely reading your posts with great interest, Jacque, and I hope that the recent return of your fatigue and symptoms is just a temporary blip on the path to much better health.

I guess I am thinking ahead a bit. But if rituximab does turn out to work for most people with ME/CFS, then we will need to think of good ways to make it easy to do and relatively affordable.

Anyway, I have always wanted to travel to and spend some time in Asia !

Do you know what mg dose of rituximab you are getting in each infusion, by the way? Is the dose around the 1000 mg mark that seems to be used in the Fluge/Mella study, or are you getting more or less than that? And is the time interval between the infusions you are getting also a couple of weeks like in the Fluge/Mella study? Or are your 6 infusions going to be stretched across a longer time, like a year or so? Just wondered what approach your doctors are taking.
Had first two infusions over 2 weeks and have 4 more over next 13? months I believe... Don't know the amount I am getting... Will keep you posted.
 

redo

Senior Member
Messages
874
Speaking of which, your quote from the Norwegians is very interesting because up until reading that I'd assumed they were only pushing the autoantibody explanation. That requires the pre-existing autoantibodies and the plasma cells producing them to disappear over a timeframe that likely takes months. Jacque's fast response reported here on PR is the opposite - pointing at altered signalling instead.
(...)
Yes, kindly let me know via PM about your Enbrel experiences. Btw, one can apparently order Reditux and have it shipped anywhere, including to the U.S., for now. Send PM if you'd like info.

I have seen lots of RTX given in the 'infusion centers' at private practices here in the U.S. Yes, MDs (oncologists/hematologists) are present, of course. It's a big money maker and AFAIK cheaper than at a hospital. Btw, it's not quite cortisol that's given but Solumedrol, i.e., IV methylprednisolone - but that's pretty much the same thing. With IV diphenhydramine and Tylenol.

Ahh. I made a typo, it was supposed to say "-ne" where I wrote "-l". It's pretty common where I live to use the colloquialism "cortisone" for drugs in the hydrocortisone group, ranging from IV methylprednisolone to oral prednisolone.

Yes, the Norwegian team is open to every explanation. I posted a thread about it a while back, after I got a graph from a source of mine: http://forums.phoenixrising.me/index.php?threads/rituximab-the-threshold-theory.12968/
I swung it by my immunologist, presenting Mella/Fluge's thoughts about an autoantibody, and he said quite clearly that such a response had all the hallmarks of being cytokine mediated. The graph is no longer in the thread, as a moderator (mistakenly) assumed that the London Conference had copyrights. The image was from a different source. Although I think it was sloppy and a tad arrogant moderation, it's water under the bridge. I sent you a PM with the image :) . I'll ping you if/when I'll get experience with Enbrel.

I got a slight improvement immediately after both RTX infusions, and I suspected the cortisone was causing it. I'm pretty sure I got diphenhydramine along with a Tylenol, although when I asked (some weeks later) I was told it was probably cetirizine I'd got. But I seem to recall that there were to injections, and one pill. Although the improvement was moderate, diphenhydramine (or some somewhat similar drug) might've been what was causing it - as I've never improved on cetrizine before, and I did a trial of prednisolone afterwards to see if I got somewhat of an improvement from that, which I didn't (done simply to troubleshoot).

Anyone think it might be a good idea to set up an ME/CFS patients' residence or commune in say Thailand or India?
I think that's a good idea. People who thinks it's worth the risk are left with few options as it is.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
They are developing a sub-Q injection of rituximab. It's being tested in trials now. If it gts approval, I wonder how the cost will compare with IV? I would think it would be somewhat less and maybe no need to go to the hospital at all or just on the initial shot maybe.

http://www.roche.com/media/media_releases/med-cor-2012-12-08b.htm
Yes, normally you'd expect the large antibody molecules to get stuck in the interstitial space and never get into the bloodstream. But that new method uses a way to break down the barrier and let the RTX get free into the blood.

I'd expect the infusion industry to fight subQ injection by saying it's not safe to take it and run. You're very astute on the first shot being different, because that's when there are the most numbers of B-cells plus you'd find any anti-rodent allergy then.