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Palmyra
07-16-2010, 12:40 AM
All of our Weg hero docs have finally gotten a significant paper reported in the New England Journal of Medicine regarding a multi-centered trial comparison of Cytoxin vs Rituxin in obtaining disease remission in ANCA associated vascultis. You will be familiar with all the authour names....its like an all star game!


Rituximab and Cyclophosphamide: A Tale of Two Treatments | Now@NEJM (http://blogs.nejm.org/now/index.php/rituximab-and-cyclophosphamide-a-tale-of-two-treatments/2010/07/14/)

This is the first published study on a new med to treat Weg in 40 years. Big news. Will hope it will also bring attention to the medical community at large, about this disease, and the growing numbers of those affected by Autoimmune Disease in general.

Sangye
07-16-2010, 11:19 AM
Thanks for posting that-- very exciting to get Wegs research into NEJM.

The editorial link in the article had my favorite line, "For now, RITUXIVAS and RAVE lend hope for our patients that targeted therapy may quell this B-cell–driven autoimmune disease."

May it be so.

drz
07-16-2010, 12:24 PM
Rituximab seemed to have more side effects but slight better remission rate. Death rate was same for both of 18%. Like one of my colleagues said to me "if you survive the treatment, it will get better.

I wonder when Mayo at Rochester will publish their results of treatment with Rituximab.

pberggren1
07-16-2010, 06:00 PM
Is this Rituxivas and Rave the same as Rituximab and Rituxan?

Sangye
07-16-2010, 10:41 PM
RITUXIVAS and RAVE were the names of the 2 trials discussed in the article.

The cool thing is that since the RAVE study (the more recent of the two), the Wegs docs are using it more and much more data is coming in.

Dr Seo said that for straight kidney involvement, rtx has no advantage over ctx for inducing remission. (He also said involvement isolated to the kidneys was "easy" to get under control-- the easiest of all)

But for relapsing Wegs and refractory (non-responsive), rtx is significantly better than ctx. My refractory Wegs sure wasn't willing to negotiate with any drug but rtx. :D

Palmyra
07-18-2010, 01:45 AM
Confusing, but would love to hear more thoughts on this subject......

As per my understanding:

There were two studies published in this most recent New England Journal of Medicine, both comparing the use of cytoxin vs Rituxin for the treatment of ANCA related vascultis. One was conducted in England, titled "Rtuxivas" and the other was a muti-centered trial entitled "RAVE". The RAVE trial's lead clinician was Ulrich Specks,MD of the Mayo Clinic. The author was Stone, MD of Boston, MA. The "RAVE" trials were conducted at multiple hospital sites throughout the USA, including the Mayo Clinic, Rochester.

My daughter just recently saw Dr Specks for treatment....his opinion seems to be similar to Dr Seo as Sangye related previously, that Rituxin may have less morbidity/side effects than cytoxin when used to treat refractory disease. Important to note that cytoxin in this particular study was 'oral', and may therefore have a higher incidence of toxicity. Yet to be addressed is what long term effects of Rituxin therapy may be, and if a sustained remission is possible with this treatment.

drz
07-18-2010, 10:27 AM
RITUXIVAS and RAVE were the names of the 2 trials discussed in the article.

The cool thing is that since the RAVE study (the more recent of the two), the Wegs docs are using it more and much more data is coming in.

Dr Seo said that for straight kidney involvement, rtx has no advantage over ctx for inducing remission. (He also said involvement isolated to the kidneys was "easy" to get under control-- the easiest of all)

But for relapsing Wegs and refractory (non-responsive), rtx is significantly better than ctx. My refractory Wegs sure wasn't willing to negotiate with any drug but rtx. :D

The doctors tried me first on Rituxan but it wasn't working fast enough. Their impression from the work at Mayo in Rochester was that it might have less side effects but the the study above doesn't support that view. The doctors on my teams at the U of M Medical Center said they could try Rituxan first and if it didn't work go to Cytoxan which is what they did. The doctors said they could not do the reverse though.

Palmyra
07-18-2010, 01:00 PM
I can understand how serious, acute disease may not respond rapidly enough for Rituxin treatment. Cytoxin and plasmapherisis still has a place for severe/acute disease. What is to be said for long term maintenance and medically induced remission? I think those are for a later major study, yet to be determined. Much to learn.

My daughter was fortunate in disease diagnosis/control to use Rituxin as a primary response after 5+ months of poor response to pred/methotrx treatment and an early diagnosis.....holding the really bad symptoms at bay, until U. Specks,MD suggested Rituxin as a primary treatment tool.

It has worked for her and has so far (for four years!) and she has had no serious side effects exception of immunosuppression and related opportunistic infection.

Thanks for your input, as this is a great msg board. Really pleased with the group :-)

Palmyra-Jane, hoping to climb Long's Peak in mid-August...but buying trip insurance none the less!

Palmyra
07-18-2010, 01:03 PM
The cool thing is that since the RAVE study (the more recent of the two), the Wegs docs are using it more and much more data is coming in.

Sangye
07-18-2010, 11:08 PM
The doctors on my teams at the U of M Medical Center said they could try Rituxan first and if it didn't work go to Cytoxan which is what they did. The doctors said they could not do the reverse though.
Since rtx destroys all the B cells for 6-12 months, you couldn't jump onto ctx until you had some B cell recovery. For most people in need of a big drug, that lag time is way too long.

I think as they get more data on long-term rtx use they'll be better able to compare side effects. The RAVE study only followed people for 6 months. If I'm interpreting this correctly, that would only allow them to compare the initial 6 months of side effects for each drug. Many of ctx's worst side effects and damage come later on.

Jack
07-19-2010, 02:30 AM
Many of ctx's worst side effects and damage come later on.
I don't even like to think about it, its like a time bomb ticking away inside and I know I've had more than my fair share of the stuff. :(

Never mind - live in the present and deal with the now I say! :)

LisaMarie
07-19-2010, 04:43 AM
I don't even like to think about it, its like a time bomb ticking away inside and I know I've had more than my fair share of the stuff. :(

Never mind - live in the present and deal with the now I say! :)
jack...please write a book of all your wit and experiences....thanks for picking me up during one of my funcky blue days ...suppose to start Iv ctx next week...doc says it is safer than the daily po one...heading to the beach to put my
feet in the sand and ocean and mediate have a great day...head back to missouri on tuesday

Sangye
07-19-2010, 07:53 AM
I don't even like to think about it, its like a time bomb ticking away inside and I know I've had more than my fair share of the stuff. :(

Never mind - live in the present and deal with the now I say! :)
Good attitude!

I like this quote by Mark Twain:
"I've been through some terrible things in my life, some of which actually happened."

I'm working on that these days. :)

Palmyra
07-19-2010, 08:26 AM
Very astute observations there Sangye, re not being able to jump onto another drug....but wouldn't it be the same either way? Nope, just answered my own question...ctx is out of the system much sooner, making other treatment choices available much sooner. What aspects of the immune system are affected by ctx? Is it a pretty broad sweep?

Sangye
07-19-2010, 08:48 AM
Sometimes the Wegs docs begin ctx and then add in rtx within a couple weeks. This helps "cover" for the rtx lag time of about a month. We tried that last October but the ctx was too toxic for me and we had to stop it. The rtx kicked in just in time.

The reason why they use ctx for Wegs is because it's so toxic to the body that it winds up suppressing the immune system. They take advantage of this side effect. It's a bad choice to have to make-- damage the entire body just to affect one area. This is what's motivating the research to find more targeted therapies like rtx, etanercept, cellcept, etc....

Rtx selectively destroys the B cells--not even all WBCs. It has no direct effect at all on other tissues like chemo does.

Sangye
07-19-2010, 08:51 AM
I think ctx and rtx came out roughly equal in terms of adverse events (eg, infection, allergic reaction, fever, malignancy) in the first 6 months because these are all unavoidable with any strong immunosuppressant. It didn't surprise me, anyway!

Like I said, I think the real difference is going to be seen as they compare long-term adverse events.

LisaMarie
07-19-2010, 11:22 AM
keep teaching please....you r such a wealth
of info and really keep me positive thank you

Palmyra
07-19-2010, 11:39 AM
Like I said, I think the real difference is going to be seen as they compare long-term adverse events.

(Still getting the hang of all of the impressive features of this site mastered with my feeble middle aged brain:rolleyes: , so forgive my mistakes while I learn).

I have a modest grip on the affect and mode of action of rtx. My daughter was never given ctx, so I haven't done the research. She is one of the newbies, that was never placed on the most recent cocktail treatment of Pred/ctx....she was diagnosed early prior to the onset of really severe disease, and was launched with rtx. I quess I should be really glad about that.

And Sangye, I can't imagine how long it may take to get a trial of that type coordinated, and enough participants involved to make it valid. I am quite sure Genetech is all over it like white on rice!

Thanks!

Sangye
07-20-2010, 01:13 AM
Yes, just avoiding pred is a major accomplishment!

Rtx has been in use for certain cancers for quite some time and has a good track record of safety, even though they use much more of it than with Wegs. My JHU hematologist said they routinely give 16 infusions in a row! There's no telling how this will all shake out. I'm just grateful I got on rtx.

Palmyra
07-20-2010, 01:41 AM
Well, she wasn't that lucky...she did have to endure the 6+ months of pred until the rtx was engaged and working. Just trying to avoid the pred again, and figure out what her 'flare cycle' is. (Appears to be ~6-9 months)

Her local rheumy is very reluctant to monitor B-cells and employ rtx routinely. (!?) She mentioned fear of PML and that unproven track record. So back up to Mayo to get a written treatment plan delivered to the local. The locals can't possibly be up to speed on ALL the diseases they treat...the VF specialists are usually at academic institutions, and typically vasculitis is all they treat.

Sangye, you see a great team at JH's...my daughter sees Speck's/Mayo....what appears to be the difference in treatment coming out of the CC? (Langford,et al)? Good question for the group at large. What treatment recommendations seem to be coming out of the Cleveland Clinic currently?

Thanks for the reminder that rtx has been around for years as a treatment for NHL and CLL, and at much higher/prolonged doses. Her VF specialist (Dr Specks, Mayo,) suggested that PML occurs with many immunosuppressive agents,and then only rarely, and appears to be more common with multi-drug therapy. He and Mayo rheumy took her off mtx as they considered it unnecessary (wasn't helping with joint pain) and was complicating her immune burden.

Sangye
07-20-2010, 02:01 AM
PML... Yes, it's a risk but it's also so rare. And you're right-- it can happen with any immune-suppressant or with anyone who is immune-compromised (eg HIV/AIDS). Even CellCept carries an FDA black box warning about it. It seems ridiculous to me for a doc to want to limit a drug that carries a very remote risk, when Wegs is 100% damaging and deadly. Dr Seo made sure I knew about PML, but has not expressed further concern than that.

From what I've seen on here, it looks like treatment recommendations from all the major centers are generally in line with each other.