Still puzzeling over diverse dosages of Rituxan

[me2]

So here is an article that makes me scratch my head some more (which I can really feel now with thinning hair)
Low dose use of Rituxan for an autoimmune disorder. Ok Al, if you are watching, just dive in and explain all this for me. Or anybody, I would even listen to aliens at this point.
Really, I'm not quite grasping the mechanism of Rituxan treatment and use.
And now I know even less

Low-dose rituximab plus steroids demonstrated safety, efficacy in autoimmune hemolytic anemia | HemOncToday (http://www.hemonctoday.com/article.aspx?rid=95429)

[pberggren1]

I'm not sure what you are asking here. Rtx has already been proven for use in Wegs as a main drug to get it into remission. It of course does not work as fast as ctx but is much less toxic.

[Chris G]

If your question is.....why do there seem to be so many different dosing guidelines........part of the confusion may be due to the fact that the article is not related to wg. The disease they're discussing, seems to respond to rtx treatment at much lower doses than we need.

Generally we receive either 2,000mg rtx via 2 infusions (1,000mg each), OR 3,000 mg rtx via 4 infusions (750 each). Some docs think 2,000 mg is enough (and in some cases it is enough). But in some cases, it is not. For example, larger people may to require more than 2,000 mg. Also, some people have more stubborn wg, and require more than 2,000 mg (I seem to be in this group).

Some docs prefer to go right by the book, and they stick with the method which was proven in trials - 3,000 mg 4 infusion.

[me2]

Can't you read my mind? I'm on prednisone ya know and I have super mental powers.
I was continuing a discussion from another thread that has been going on in my mind.
You are right Chris about the dosage guidelines you state so well. But add that there are strange people out there also getting a 6 month dosage of only 1,000 mg - me. My doc says he knows someone in the UK who has been doing this for a long time and has had good results.
I guess I'm trying to get clear on how Rituxan is working. Sangye says , I think, that she was told it takes out circulating B cells which amount to 10% of total cells. I may have it wrong but it was something like that. I know she was saying that it doesn't take out all B cells everywhere - so how does it work? And how can it work in the case I found above? Unfortunately they don't define 'low dose'. I may try and find the whole study at the University library where I go for treatment.

The reason I am persuing this is to bring some of this knowlege and awareness together for us patients so we can make our own decisions. If I go to Dr A and get 4 infusions every six months and Dr B would give me 1 infusion every six months - which Dr is doing the proper treatment and based on what criteria? The difference here is a factor of 4. That is HUGE. I want to know the criteria and all the risk factors so I can decide myself how I want to be treated. I know of no where I can educate myself on this.

And you are right too Chris that this article is not about WG but it IS about how Rituxan is being used and that MAY become relevant to WG. WG drugs and knowledge was mostly gleaned from stuff they were doing to help OTHER conditions. So it keeps me curious.
It is surprising to me that it has a use at 'low dose'. When Rituxan was first used for WG it was only done using the 4 dose protocol. Now there are a lot people using 2. Now there is at least 1 person (me) only using 1 dose.

I assume the issue is much like the evolution of the use Cytoxan. Cytoxan in the early days of WG treatment (mid to late 70's) was given for two years initially ( I know because I was on it) and now they have whittled it down to months. Its possible that at the time I recieved treatment there were already Dr's that knew you didn't need to use so much just like now there are Dr's using different doseages of Rituxan. Not just a little different either - I know Sangye has mentioned weight as one variable but even that concerns me, I've been on prednisone a long time and I am not skinny and svelt, yet I am getting 1 infusion at six months. Where is it written someone of weight 'X' gets dose 'B'?

I've tried getting my doc to discuss these issues and he is not much help for whatever reason. Maybe he thinks I don't trust him. Quite the opposite , I'm letting him treat me in a way that none of the other 'big giant head' WG Dr's are - very differently.

So, I want to understand these things much more so I can decide myself and whatever these criteria are it would be good for others to know so they can make their own decisions if they want to. I could choose a particular Dr that I think is great and just do whatever they say but even that is not as good, in my experience, as having my own understanding and making the decision myself.

I wish the symposium were closer and I could corner one of the 'big giant heads'. I did that at one symposium many years ago and I forget what I asked this doc in the hall way but his answer I remember clearly (Dr Specks) "You live on the wrong coast to have vasculiuis. All the research is being done out here. You live in a good place to have a heart attack"

What he was doing was explaining in plain terms was why it was so hard to find a top level doc on the West coast. Before that, I didn't realize that different areas of research are centered in different areas of the country and because of that your level of treatment could vary widely. My dad later had a heart attack - and boy did he get good care. Not only that I was able to relax a little knowing he was in a geographic area of top notch heart docs. But now I'm off the subject.

If anyone can steer me to the cutting edge literature that can explain the wide variance in protocol I'd appreciate it. And I'd come back and let ya know what I found. So far I don't know much. I know whats being done - I want to know why. AND are the results being tracked somehow. Who is keeping track of the success of using 1 dose every six months? It would be good to know the actual results because it could change how others get care.

In another thread we talked (I'm sorry I forget who I was talking with) about developing resistance to Rituxan. What rate does this happen at and at what doseages? I want a chart I can look at so I can decide which direction I'm taking risk in. Right now I suspect my doc is risking low dose follow ups with me to help prevent resistance from happening- but I'm just guessing. I don't like guessing about really important things.

[me2]

Ok, I just looked at how much I wrote. I will reduce my dose of prednisone tomorrow.

[pberggren1]

me2, the mothership says they need to talk to you ASAP.

[me2]

Ha, thanks Phil. I had my foil hat on and missed the message.

[Al]

I'm not sure I can tell you the best coast to live on, Kirk. Personally, I wouldn't want to get a heart attack just to prove that I can get the best care. Anyway, there are always pluses and minuses: They get blizzards; we get floods. They get hurricanes and tornadoes; we get earthquakes and volcanoes. We get brown grass in the summer; their grass looks green from here.

I did read the article, which I found interesting, though it left a lot of questions in my mind. How it relates to an RTX protocol for WG is: it doesn't--probably, since it was about a different ailment altogether. Autoimmume hemolytic anemia is, though, an autoimmune disease that is sometimes associated with other AI syndromes. It occurs when certain antibodies attack erythrocytes (red blood cells), leaving a deficit available for carrying hemoglobin. As in the case with many other AI diseases, the standard treatment calls for modulating the immune system. Rituximab (RTX) works by targeting B cells--specifically, plasma effector B cells (those in the lymphatic system are fairly well protected, and memory B cells live a long time). As antibodies are manufactured by the B cells, keeping those cells from cloning rapidly will tend to suppress the various antibody populations (including the ANCA population). This article describes a novel protocol, however, that uses "low dose rituximab" with added steroids. But I couldn't tell exactly how the protocol was carried out. It is possible, I suppose, that a similar protocol could be effectively employed for WG, But that would be a hypothesis that would have to be tested on its own.

Anyway, Kirk, I'm glad to see that your steroidal muse is on duty!

Al

[Dryhill]

me2 you state "My doc says he knows someone in the UK who has been doing this for a long time and has had good results" . I believe Dr. Jayne at Addenbrookes Hospital, Cambridge (the UK's leading centre for Vasculitis research) has had quite a bit of success with administering five infusions of RTX, one infusion is given every six months for two years.

I doubt you will find the sort of information you want as different doctors/hospitals have different ideas as to the best treatment. My doctor wanted me to have four infusions (he seems to think I am a trifle overweight, damn cheek I am not quite 300lbs so almost a stick!) but the accountants that run the hospital and clearly know best said no only two infusions.

Jim

[Al]

me2 you state "My doc says he knows someone in the UK who has been doing this for a long time and has had good results" . I believe Dr. Jayne at Addenbrookes Hospital, Cambridge (the UK's leading centre for Vasculitis research) has had quite a bit of success with administering five infusions of RTX, one infusion is given every six months for two years.

I doubt you will find the sort of information you want as different doctors/hospitals have different ideas as to the best treatment. My doctor wanted me to have four infusions (he seems to think I am a trifle overweight, damn cheek I am not quite 300lbs so almost a stick!) but the accountants that run the hospital and clearly know best said no only two infusions.

Jim


But, hey, Jim--if you have an accounting problem, I guess you live on the right coast....

Al

[Dryhill]

But, hey, Jim--if you have an accounting problem, I guess you live on the right coast....

Al

But Al, as you know I live half way between London and the south coast. Mind you a large proportion of the working population of this village` (with the surrounding farms there are just over one thousand homes) work in The City and are therefore probably involved in finance and used to the new fangled abaci. :tongue1:

Jim

[Al]

But Al, as you know I live half way between London and the south coast. Mind you a large proportion of the working population of this village` (with the surrounding farms there are just over one thousand homes) work in The City and are therefore probably involved in finance and used to the new fangled abaci. :tongue1:

Jim


So, Jim, if they don't account for you to your satisfaction, you can head to the real coast--say Brighton or Eastbourne, where, I think, they like a different kind of abacus....

Al

[Dryhill]

So, Jim, if they don't account for you to your satisfaction, you can head to the real coast--say Brighton or Eastbourne, where, I think, they like a different kind of abacus....

Al

You are right about Brightron Al, definately not my kind of abacus. Based on recent news broadcasts it looks as though Eastbourne is for retired clergy who used to be very friendly with choir boys, if you get my meaning.

Jim

[me2]

Associations with choir boys aside... ( how did my questions devolve into that?)
I am going to keep pursing this line of questioning. Dryhill, its funny because when my doc said 'somebody in England' , I asked if it was Dr Jayne. He said he didn't remember.
Well, that inspires confidence in a source.
I emailed Dr Jayne many years ago, before Rituxan was available here , and he expressed himself with refreshing candor.
Thanks for the thoughtful responses. I'm not done with this yet.

[Sangye]

Just a correction about how much rtx is received in the different protocols:
In the 2-infusion protocol, the amount you get is not based on your weight. Everyone gets 1,000 mg rtx each time.

In the 4-infusion protocol, the amount you get is based on your weight.

[freakyschizogirl]

me2 you state "My doc says he knows someone in the UK who has been doing this for a long time and has had good results" . I believe Dr. Jayne at Addenbrookes Hospital, Cambridge (the UK's leading centre for Vasculitis research) has had quite a bit of success with administering five infusions of RTX, one infusion is given every six months for two years.

I doubt you will find the sort of information you want as different doctors/hospitals have different ideas as to the best treatment. My doctor wanted me to have four infusions (he seems to think I am a trifle overweight, damn cheek I am not quite 300lbs so almost a stick!) but the accountants that run the hospital and clearly know best said no only two infusions.

Jim


I'll throw my 2 cents in since i am under Addenbrooks and have met Dr Jayne, he was the one who referred me for RTX. He said 2 infusions 2 weeks apart were best for me with maintence doese every 6 months for 2 years. I think this varies from person to person tho, depends on disease activity, weight and a fwe other factors.

Geoff's also just had some RTX so i wonder if he's had the same as me...

[me2]

Just a correction about how much rtx is received in the different protocols:
In the 2-infusion protocol, the amount you get is not based on your weight. Everyone gets 1,000 mg rtx each time.

In the 4-infusion protocol, the amount you get is based on your weight.

Ok that makes it even more confusing. Thanks for clarifying - I think? ha

I'm gonna have more questions.

Freaky what is your maintenance dose? 1 infusion or 2 ?

[Dryhill]

Just a correction about how much rtx is received in the different protocols:
In the 2-infusion protocol, the amount you get is not based on your weight. Everyone gets 1,000 mg rtx each time.

In the 4-infusion protocol, the amount you get is based on your weight.

My doctor wanted to give me four infusions of 750mg which over the four weeks would have been 3,000mg. He based this on my weight and how active the Weggie dog has been. Having said that a week after the first infusion things have started to calm down a bit, so I now have my fingers and toes crossed (mind you walking with crossed toes is a trifle odd).

Jim

[Sangye]

Last year I tried to do a 2-infusion treatment, as we planned to repeat it every 6 months indefinitely. It didn't work. I had to do my usual 4-infusion treatment right on top of it, which we plan to repeat every year if I can make it that long.

Kirk, what confused you?

[me2]

Well Sangye I'm really trying to wrap my head around decisions are made with the Rituxan protocols. My theory is that with better understanding I can better keep tabs on my therapy. When you say the 2 infusion protocol is not based on weight and the 4 infusioin protocol is my brain sees apples and oranges (thanks to prednisone confusion manifests itself in food based images).

What rational treats one patient by weight and another with what seems like an arbitrary treatment dose. I'm really in the dark , as you can see. I want to know how these ideas were developed and based on what studies (if any).
It seems like there is a lot of ideas being used behind the scenes to decide treatment protocols and its not something my docotor talks to me about. Don't get me wrong, I think I'm getting good care and I'm betting others are too but without a true and deep understanding of how this works there is more faith in the system than I am comfortable with.
I want enough information and understanding to be evaluating and deciding treatment on the same level as my doctor , or say
Dr Langford.

There have been times in the past where my own understanding has saved my bacon or allowed me to help someone else to ask some good questions that change the course of treatment.

So, why treat the same person with one protocol based on weight one time and with another protocol not based on weight the second time.

It seems to me there are refinements of treatment going on with Rituxan much like happened with Cytoxan but with different criteria and I'd like to be right in the know. I'm nosey. I wanna be knowsey. (thats dumb , but I'm gonna leave it. )

I do my 1 infusion treatment tomorrow. I will be very curious what the three month forecast is on that.

I hope you are doing well Sangye. Overall my health has improved although its taken over ten years to happen. Can you believe that?? What kind of person can survive staying sick for ten years?
Sometimes on good days I find myself thinking "I hope Sangye is slowly getting better too. I know she has been on the magic mountain ride for some time too and could use a break."

[Al]

Kirk, I can't tell you how the decisions are made, but it does seem that the protocols are in a state of flux, even for those who design the protocols. And that is not your average clinician, who just reads the literature and goes along with whatever protocol seems appropriate--at least until it doesn't work so well. (The average clinician does not see enough patients with an ailment like WG to get a good feel for what works best. This sense takes a great deal of experience. This, by the way, is one reason why you have to sometimes leap in to save your own bacon.

I hope you do well tomorrow. I'll wave when I pass the University Hospital (I'm assuming that is where the infusion is being done.) Please give us a report when you can.

Al

[me2]

Thanks Al. I'm on the fourth floor. I'll watch out the window for someone swerving erratically.

[Sangye]

Well Sangye I'm really trying to wrap my head around decisions are made with the Rituxan protocols. My theory is that with better understanding I can better keep tabs on my therapy. When you say the 2 infusion protocol is not based on weight and the 4 infusioin protocol is my brain sees apples and oranges (thanks to prednisone confusion manifests itself in food based images).

What rational treats one patient by weight and another with what seems like an arbitrary treatment dose. I'm really in the dark , as you can see. I want to know how these ideas were developed and based on what studies (if any).
It seems like there is a lot of ideas being used behind the scenes to decide treatment protocols and its not something my docotor talks to me about. Don't get me wrong, I think I'm getting good care and I'm betting others are too but without a true and deep understanding of how this works there is more faith in the system than I am comfortable with.
I want enough information and understanding to be evaluating and deciding treatment on the same level as my doctor , or say
Dr Langford.

There have been times in the past where my own understanding has saved my bacon or allowed me to help someone else to ask some good questions that change the course of treatment.

So, why treat the same person with one protocol based on weight one time and with another protocol not based on weight the second time.

It seems to me there are refinements of treatment going on with Rituxan much like happened with Cytoxan but with different criteria and I'd like to be right in the know. I'm nosey. I wanna be knowsey. (thats dumb , but I'm gonna leave it. )

I do my 1 infusion treatment tomorrow. I will be very curious what the three month forecast is on that.

I hope you are doing well Sangye. Overall my health has improved although its taken over ten years to happen. Can you believe that?? What kind of person can survive staying sick for ten years?
Sometimes on good days I find myself thinking "I hope Sangye is slowly getting better too. I know she has been on the magic mountain ride for some time too and could use a break."

Because rtx hasn't been used for Wegs that much, it's still a guessing game for a doctor to choose an infusion protocol. The RAVE trial was done using 4 infusions. The standard protocol for treating RA has been the 2-infusion protocol. As they've used rtx more and more to treat Wegs, they're finding they can use 2 infusions for many patients.

Unless the patient is very overweight, the 2-infusion protocol is a bit less rtx than the 4-infusions, allowing us to be exposed to the least amount of rtx as possible and still get the maximum benefit. If someone is very overweight, the difference between the two protocol doses is much greater and may not give the same result.

Also thrown into the mix is the severity of Wegs, how responsive it's been to other treatments and the type of involvement. Weggies tend toward either granulomas or hemorrhaging. Granulomas are much easier to treat. Of all the Wegs manifestations, alveolar hemorrhaging is the most severe and tends to be the most refractory to treatment. That's the type I have and it sure lives up to its reputation! I'm also quite overweight. Alveolar hemorrhage + refractory + overweight = Highest dose of rtx needed.

Does that help?

(something to ponder as you get your rtx :smile1: )

[Sangye]

Thanks for the good wishes, Kirk. I'm glad that you're crawling out of the hole the Wegs dog dug for you. :thumbsup:

Compared to where I was in 2006 (dx) I'm way better--different ballpark. But I haven't made progress in the past couple years. In fact, as far as exercise goes I'm not even close to where I was in November, 2010 when the Wegs dog started waking up and we waited several months to treat it. I feel like the rtx is losing steam each time. I saw Dr Seo last week and for the first time he didn't make a point of disagreeing with that. I'm struggling with tapering the hydocortisone but that is another story. All in all, I'm just not feeling very hopeful these days.

[Al]

How did it go, Kirk?

Al

[me2]

Doing good thanks Al. Someone in a blue dodge waved at me and I yelled "Hi Al"
Easiest infusion yet. I don't know if thats a good thing or not. Headache and tired today but not bad at all. There is a flu bug going around that is worse than this. (I haven't gotten it- imagine that)

Sangye, I too am having trouble with the prednisone taper. I feel like I'm really, really stuck at 15 mg. My hope of course is that my Rituxan booster shot will put some steam behind further reduction and recovery.
If its any consolation I have been fighting my latest battle for over ten years now and seem to be getting better for no particular reason the past few months. I seem to be doing everything the same except for the lower dose of Rituxan which doesn't make sense.
I hope to return to part time work this summer for the first time in a very long time. Like many here leaving work has been one of the most painful side effects.

[Al]

Hey, do I seem like I drive a blue Dodge??!! But I did wave; maybe you were dealing with the nurses or something....

I'm with you about the psychological nastiness of this business, and the need to keep on truckin'. Hang in there, my friend, and stay away from the flu bugs.

Al

[KathyB]

After completing the first treatment of 4 x 4weeks, I am trying the 2 x 2 wks this round (starts Tues). I handled the first round perfectly and am hoping this next round will go just as well. My rheumy says he's been following other studies and wants to try this protocol. I'm game and will let you know how it goes!

KB

[Sangye]

Sangye, I too am having trouble with the prednisone taper. I feel like I'm really, really stuck at 15 mg. My hope of course is that my Rituxan booster shot will put some steam behind further reduction and recovery.
If its any consolation I have been fighting my latest battle for over ten years now and seem to be getting better for no particular reason the past few months. I seem to be doing everything the same except for the lower dose of Rituxan which doesn't make sense.
I hope to return to part time work this summer for the first time in a very long time. Like many here leaving work has been one of the most painful side effects.
It makes me so happy to hear that you're doing well, Kirk. Maybe the rtx is just what was needed to sing the Wegs dog to sleep? Going back to work-- wow. Good for you! :thumbsup:

[freakyschizogirl]

Ok that makes it even more confusing. Thanks for clarifying - I think? ha

I'm gonna have more questions.

Freaky what is your maintenance dose? 1 infusion or 2 ?

1 infusion every 6 months for 2 years

[Sangye]

One infusion??!! :blink:

The Wegs dog that camps on my porch lifts up his nose and howls with laughter. That wouldn't even be enough to get him to sit down, much less fall asleep. :laugh:

[freakyschizogirl]

lol Sangye.

As my symptoms arnt as strong as some peoples i trust this will work out fine.

First maintenance does it at the end of April!

[Sangye]

I'm sure it'll be enough for you. Your Wegs dog is much more reasonable about nap time.

[Lightwarrior]

One infusion??!! :blink:

The Wegs dog that camps on my porch lifts up his nose and howls with laughter. That wouldn't even be enough to get him to sit down, much less fall asleep. :laugh:

My wish for you never comes true. I want that damn dog to fall into a deep sleep for a very long time.

[drz]

My wish for you never comes true. I want that damn dog to fall into a deep sleep for a very long time.

I think hers suffers from insomnia. Now if we could find a cure for him?????:sneaky:

[Sangye]

LOL! I wish I could train the Wegs dog to behave as well as my "other" dogs. When I turn off the light at night they go to sleep. No one gets up and starts running amok. They sleep. Like good dogs. You hear that, Weggie dog? Sleeeeeeeep!! :wink1:

[Al]

LOL! I wish I could train the Wegs dog to behave as well as my "other" dogs. When I turn off the light at night they go to sleep. No one gets up and starts running amok. They sleep. Like good dogs. You hear that, Weggie dog? Sleeeeeeeep!!
My experience with household pets is that they invariably get active at the crack of doom (like before 9:00 AM) to tell me that they are hungry. (In my world, breakfast should come about noon.) I wouldn't want Wags the Wegs dog to beg for attention in that way.

Al

[Sangye]

None of my dogs have ever been annoying like that. People often unwittingly train their dogs to wake them up, beg to go out early in the morning, etc... My dogs get up when they see me waking up. My wake-up time differs greatly from day to day, and they just roll with it.