Rituximab in US- Dr. Kogelnik.

[ScottB]

Any idea when the Patent runs out and on average how much cheaper Rituximab might be when it is generic?

I ask not because I would be able to access it privately but because I wonder how likely it is the NHS (NICE) would approve this drug were its efficacy to be proven.

The patent in the United States runs out in 2015.  There is another drug company, Indian I think, that is working on producing a generic.  The cost savings, however, are not expected to be as great as one normally expects because the manufacturing process is so expensive.  The company that owns the rituximab patent will not be doing any further clinical trials with it but are developing a drug that is slightly different that can be granted a new patent, this despite the fact that rituximab is been shown to be safer than the new one.

See:  http://neuroimmunology.wordpress.com/2011/03/27/the-shameful-story-of-rituximab-in-multiple-sclerosis/

[Tango]

Frankly I'm more ashamed that people let one or two questionable decisions or opinions taint their entire opinion of doctors who are working for us to find a solution. Its not as though he suggested it is a psychological condition or that we have yuppie flu.

At a certain point it must be frustrating for these doctors to have their names dragged through the mud by the very people they are trying to help.

Kogelnik has done a better job of securing funding for productive research and legitimizing our condition than almost anyone else i can think of, he and Montoya are a blessing.

I said its a shame. Who's comment did you read? He can easily take his name off the paper.  Do you not think he should?

[Jackie]

alpha and cytokine (re your interesting possible theory about ritux/arv) - just a little tidbit and i dont know if it will help much, but i can tell you what went wrong with ME during my arv trial (unfortunately this is my unscientific explanation - i was already too ill to listen or care by the time my doc gave me the scientific one - and i didnt write it down as i usually do).

i was given very high dose acyclovir (for about 5 yrs) - THEN i was started on the ARV (as an experiment i was given EPIVIR/3TC/lamivudine because all the other standard ARV's were being tried - and epivir was thought to cause lesser side effects - be easier to tolerate - as it is often used with very ill AIDS patients...so my doc figured it might ultimately be safer for ME patients.)

anyway...i responded very quickly to the ARV, within about 6 wks (side effects were there, but not intolerable)...my memory and cognition began to return (i could read, mentally multitask, memorize things, make decisions, no brain fog at all...and that just got better and better  - sort of miraculously better - almost unbelievable. also - though none of my docs think their is any connection, it IS weird - my lipid panel and c-reactive protein levels returned to perfect normal - after years of being dangerously high. who knows why?)

BUT i also began to exhibit so many viral signs. chronic shingles (worse than ever), HSV-1 (in my mouth, so i couldnt even eat), and enteroviral rashes. but i didnt care because my brain was working so well.

i was warned that the drug would stop working (estimation was at about 5-6 months at most and that another drug would need to be added - you never take away with arvs - you just keep adding) and the idea was to choose tenofovir (it was enough alike and yet enough different from epivir to be ok to add. sorry this is all in laymens terms - but there is scientific basis for what im saying - i just cant remember how to tell it).

then it was obvious that things were not going well (i was so sick by then and couldnt have tolerated tenofovir)...i begged doc for a few more months to see if we could do something to tweak epivir into working a little longer...and so we decided to add the chinese herb immune modulator equilibrant (most people had stopped using oxymatrine because it was so unpredictable and hard to take)...but all hell broke loose then.

my body sttarted clearing viruses way too fast for my I.S. to keep up with and thats when i became "toxic". and so, at about 10 months into my protocol,  i had to discontinue epivir and equilibrant...quickly, over a three day titration period.

(though i can never stop taking acyclovir, now  - which is ok as it has a long track record with HIV patients - some as many as 20 yrs  though NOT at the high dose i take. thats problematic - and if we can stabilize me over time - we'll try to titrate down...and keep close watch on my kidney function,)

maybe you can make something out of my experience?

[Dr. Yes]

I'll take a stab at a couple of your observations, Jackie.. mind you, totally speculative ones...

anyway...i responded very quickly to the ARV, within about 6 wks (side effects were there, but not intolerable)...my memory and cognition began to return (i could read, mentally multitask, memorize things, make decisions, no brain fog at all...and that just got better and better  - sort of miraculously better - almost unbelievable. also - though none of my docs think their is any connection, it IS weird - my lipid panel and c-reactive protein levels returned to perfect normal - after years of being dangerously high. who knows why?)

We've seen studies showing vascular endothelium dysfunction in CFS patients, and we know that many inflammatory diseases can alter lipid metabolism and deposition.  We also know that some MLVs infect the vascular endothelium in mice (in brain capillaries; I don't know about elsewhere in the circulatory system).  So one could speculate that a retrovirus could trigger lipid accumulation either by: (1) directly infecting blood vessel endothelium and setting of the chain of events similar to atherosclerosis, or (2) triggering systemic inflammation from whatever area it infects, which in turn can cause lipid accumulation and endothelial dysfunction:

"Cytokine-induced metabolic effects, which include transient alterations in lipids and peripheral insulin resistance, are favorable in the short term and function as part of the host response to infection and acute inflammation to target specific metabolic fuels to and from essential organs.7 However, chronic elevation in cytokine levels, irrespective of magnitude or cause, is deleterious and promotes accelerated atherogenesis via aggravation of several risk factor pathways, including lipoprotein metabolism and insulin resistance. Indeed, even a heightened level of the low-grade chronic inflammatory response in population studies correlates with many classic and novel risk factor pathways for CHD.3,4"

[from Sattar et al 2003]

[This pattern of lipid accumulation has already been posited for other infections, including by Chlamydia pneumoniae and CMV, though not firmly established.]

One of the inflammatory factors that is commonly elevated in inflammatory diseases that can involve lipid accumulation is of course C-reactive protein.  If a retroviral infection was the root cause of the inflammatory process, an ARV that reduced its titer/expression would likely reduce circulating levels of markers like CRP.

BUT i also began to exhibit so many viral signs. chronic shingles (worse than ever), HSV-1 (in my mouth, so i couldnt even eat), and enteroviral rashes. but i didnt care because my brain was working so well.

Sorry, so far I can't think of any reason why those viruses would be activated... have their been similar reports on ARVs like epivir?

my body sttarted clearing viruses way too fast for my I.S. to keep up with and thats when i became "toxic". and so, at about 10 months into my protocol,  i had to discontinue epivir and equilibrant...quickly, over a three day titration period.

That sounds like an IRIS effect, doesn't it?  Especially if your immune system was deficient prior to taking equilibrant, its immune boosting properties may have set off an IRIS-type reaction; perhaps a (hypothetical) retrovirus also had an immunosuppressive effect which, when reduced by the lowered titer via ARVs, set you up for an IRIS reaction upon taking an immunomodulator.

Does any of that seem to fit?

[Jackie]

yes thanks doc...it does fit! i also forgot to add one very important point...a few months into the arv experiment i was having some trouble breathing (sob) so my regular m.d. did a chest xray and discovered atherosclerosis (which is sort of an unusual way to first discover it - he said if it was visible in lungs...chances were good it was also affecting my carotid artery and brain). and my neurologist says i have "small vessell disease".

but the only follow up the did was a special test to see if i have multiple myeloma (nope)...though chia is still adamant that i have an angiogram to look for cardiomyopathy? i think? (or is that pericarditis?...well, something like that - cant remember)

still battling my insurance co. over that (even if im not anxious to go through procedure). im too tired to aggressively fight them for my "rights" the way i should.

so your ideas are right on the mark. there has been enough time gone by to clear the ARV from my system - and next week i have tons of labs done. im very curious to see if my crp levels are moving back to the high-flagged area (they were carefully tracked for 3 yrs prior/up to the start of ARV - if these numbers have moved back up (to 6. or 7. or above) after discontinuation of arv - somebody may take notice!)

about the possibility of IRIS (in fact, i think you and i had this convo before)...about 2? yrs ago i went through a period where i was dead certain i was experiencing IRIS from high dose acyclovir. iris is so important, because if you survive it w/o infections - its your sign that you're moving in the right direction!

i researched and found examples of this occuring (rarely), and also in chemo patients...and chia admitted that a few of his hiv patients had it happen while taking avs AND arvs...but said no in my case. (i partly based my idea on the fact the my cd4 count had risen ABOVE the normal limit, along with worsening of symptoms...but chia said it was still not high enough to account for that)

nevertheless...this time around (with epivir) it sure FELT like everything i've read describing IRIS!


(re viral reactivations...a simple explanation i guess would be that it was a coincidence...and i dont think i read any data on this as a result of epivir, specifically).

(btw, hes not going to give epivir to john - john and i have different viruses. a few are the same, but for example he has chlamydia pneumoniae, and coxsackie2, - i dont. i have cmv - he doesnt. so, i'm overun with viruses anyway...my immune system thrown off by the introduction of a new drug...the viruses go crazy? ive had this problem to one degree or another for several yrs. ~ unpredictable.

at this point i cant be given any other experimental drugs.  the goal is to concentrate on palliative care.  im disappointed that i missed out on tenofovir - i would have liked to see the effect on the brain of taking that drug after epivir (but chia discovered some pretty ugly side effects on a few patients doing that and so we stopped)

(for me, taking rituximab is really just a pipe dream i think...though i sure would like a chance to get my teeth into something like that!)

thanks for taking a shot at this! 

[Roy]

http://bikechick06.blogspot.com/My first infusion is April 10th and e second one is April 24th. Happy, excited and looking forward to it.

[liquid sky]

Best wishes to you, Roy. Let us know how it goes, if you don't mind sharing.

[Roy]

It's Kati that is trying it. Sorry I didn't make that clear.

Someone wrote on Phoenix Rising that there is a collaborative trial in the planning stages that will be partially funded by Roche. It seems credible that this is being done behind the scenes and it sounds good to me.

 http://forums.phoenixrising.me/showthread.php?16203-Status-of-Rituximab-ME-CFS-Studies/page5

[liquid sky]

Oops, sorry. I tried your link and it didn't work. I have lost track of the beginning of the thread and didn't realize it wasn't you.

Glad to hear they are doing a trial possibly also.

[acer2000]

anyway...i responded very quickly to the ARV, within about 6 wks (side effects were there, but not intolerable)...my memory and cognition began to return (i could read, mentally multitask, memorize things, make decisions, no brain fog at all...and that just got better and better  - sort of miraculously better - almost unbelievable. also - though none of my docs think their is any connection, it IS weird - my lipid panel and c-reactive protein levels returned to perfect normal - after years of being dangerously high. who knows why?)

BUT i also began to exhibit so many viral signs. chronic shingles (worse than ever), HSV-1 (in my mouth, so i couldnt even eat), and enteroviral rashes. but i didnt care because my brain was working so well.

I know this is an old thread resurrected, but I think this is an interesting observation.

Its worth noting that "viral symptoms" aren't necessarily the direct result of viruses themselves. The symptoms are often a result of the immune response to the virus.  In the case that someone has been sick for a long time and their body has been unable to mount an effective enough immune response to clear typical viral infections, being put on ARVs and "waking up" the immune system might be expected to cause you to have the symptoms of all of those viruses at once - as your body finally starts to fight back like it should have been doing all along.

IMHO the experience reported in this thread regarding ARVs seems to lend more credibility to the idea that a retrovirus is behind the illness, MLV or otherwise. 

Your comments about the metabolic syndrome markers are also consistent with what Dr. Jamie reported in her blog for her and her daughter.  I have also noticed that since becoming ill with CFS, I have had a similarly difficult time with my lipid profile, insulin resistance, etc..

Thanks for reporting your experience Jackie.  Its very interesting...