Questions for Dr Seo

[Sangye]

I see Dr Seo next week and wanted to know if anyone has questions they'd like me to ask.Other than some specific questions about my own case, I prefer to keep the questions general so that the most people can benefit. I always ask about the latest research and new drugs.

The questions on my list so far:
1) The RAVE rtx trial used 1,000mg solumedrol for each infusion. Why are Wegs docs using less?

2) Since rtx always destroys the entire B cell population, and it's the B cells that make the trouble-making antibody, how is it possible that rtx doesn't always work?

[elephant]

Those are good questions? I can't think of any.

[me2]

'There is another...' What is that other monoclonal antibody treatment that starts with a 'G' and why is isn't it being used?

I saw a reference to it somewhere after I saw you mention it and I myself have not followed up on it. Do you know the one I mean?

[Sangye]

LOL I'm not sure, me2. Can you do a PubMed search?

[freakyschizogirl]

I was wondering if he had heard of fillers and which would he suggest is best out of Fillers or Rhinoplasty for a 1 year diagnosed weggie?

[Chris G]

Your question #2 is big on my mind right now. I sure would like to know why rtx doesn't work for some of us. Thanks for asking on behalf of the group.

[Sangye]

I was wondering if he had heard of fillers and which would he suggest is best out of Fillers or Rhinoplasty for a 1 year diagnosed weggie?
Sam, I think that's probably too specific a question. Even if I had a saddle nose and asked it, I imagine he'd say "That's a question for the ENT." LOL

[JanW]

That is totally a question for the ENT. And not just any ENT either, but one who has fixed saddle noses NOT caused by cocaine abuse. That's going to be a very rare bird indeed.

I was talking to my rheumy about the repair today, and it was clear that he knew not much at all about how it's done.

A LOT of plastic surgeons do it. It's for you to decide whether you would want to go that route, but I'd only have a WG surgeon do procedures on a part of my body that has experienced tissue death already.

[Kathie28]

I love the Rituxin question about why it does not always work. I just started round 2 last week. It's only been 5 months since I did it last so I'm really hoping it works this time. I seemed to have about 3 good months after the last round but then I got the blood clot and it all went down hill from there with symptoms creeping back up. It really has zapped the energy out of me this time.

[freakyschizogirl]

Thank Sangye, thought it was a bit cheeky, lol.

And LOL at JanW!!

[Brooke]

Just some random thoughts as I read this...
If Rituxan wipes out our b-cells, how come some people are re-treated so soon with Rituxan if their b-cells are still gone?
Sort of a question about my situation, I only had the solumedrol for the first infusion this time. I have been off of pred all year so far. (knock on wood)

[Sangye]

That's actually my case, too Brooke. I get signs/symptoms returning several months before my B cells start returning. The only thing I recall hearing once was that there might be some "hidden" B cells circulating that aren't killed off. But I'll find out for sure.

So my questions along those lines:
1) Why doesn't rtx always work?
2) How can symptoms return before the B cells return?
3) How is it that some people have one round of rtx and go into lasting remission? (ie, Why doesn't Wegs always flare once the B cells return?)

Thanks for jarring my memory about those other 2 questions!

[Sangye]

I'm also going to ask about my hypothesis regarding the 2-infusion vs 4-infusion protocol. The 4-infusion protocol has worked for me, but the 2-infusion protocol didn't. In the 2-dose protocol you get 1,000mg rtx each time, regardless of weight. In the 4-dose protocol you get 375mg/m2 based on weight. So for someone big like me, there's a big difference in total dose (2,000mg vs 3,600mg). My hypothesis is that larger people need the 4 doses.

[norcalian]

I'm really curious about number 3. Thanks for asking these questions.

[ArlaMo]

What are his thoughts on doing subsequent rtx infusions if the patient seems to be going into remission? I've seen some info that another set of infusions at 6 months out seems to be beneficial, but that wasn't in my original plan from Dr. Langford.

[delorisdoe]

I'm really curious about number 3. Thanks for asking these questions.

My answer to number 3 is...because it is wegners and thats how we roll.

[pberggren1]

I will be interested to see what Dr. Seo has to say about those questions.

[drz]

What are his thoughts on doing subsequent rtx infusions if the patient seems to be going into remission? I've seen some info that another set of infusions at 6 months out seems to be beneficial, but that wasn't in my original plan from Dr. Langford.
This is probably one of those mixed bags like the two versus four with no hard evidence on what it is more effective. I know for treating lymphoma with RTX they said they didn't know if there was any benefit in doing preventive treatments every six months or year since there is no research results to prove it either way. Some doctors still do it cause they think it might help and others don't because of risks of the side effects building up.

[Brooke]

I remember my doctor saying that for Wegener's patients they have been doing the 4 infusion. I can ask her why that is as well when I see her in Aug.

[Sangye]

Last time I saw Dr Seo (before I did the 2-infusion protocol) he said some vasculitis centers had started out doing 2 and some doing 4. They each had success so they continued doing what they were used to. He said JHU had been a 4-infusion center, but Wegs docs were finding the results were the same for both so he was using 2 more often.

[beeinformed]

Hi!

I have two questions for Dr. Seo:

1. Is it okay to be on long- term low dose prednisone (5 mg. or less) to control symptoms such as nasal /ear symptoms, for example, that otherwise would return if one were not taking the prednisone and seems to be effective in controlling these symptoms?

2. Can other autoimmune diseases such as sjogren's syndrome and/or rheumatoid arthritis, for example, co-exist with wegener's?

Sangye, I would just like to add that I think it is very thoughtful and considerate of you to ask if anyone here has a question that they would like Dr. Seo to answer!

[Sangye]

Beeinformed, I know the answers to both of those. I've been stuck at 2.5mg pred for quite some time and have asked him about that. He says anything 5mg or less is not that big a concern, though he admitted they really don't have enough info on the long-term effects of doses below 5mg. He would definitely prefer that we're off pred entirely, but if a very small dose is necessary to keep the Wegs under control then it's necessary.

In your case (as in mine right now) the question comes down to: Are your symptoms due to damage from Wegs or from active Wegs? If it isn't active Wegs (or is a very low level of activity) then that doesn't require pred. We're going to have another conversation about all this because I saw an endocrinologist recently who has some input. I'll post his response.

It's not uncommon for people with an AI disease (any type) to get another one. That's pretty well-established.

I'm happy to do this for others. :smile1:

[Sangye]

I saw Dr Seo today and got some great info. He sure is wonderful about taking the time to answer anything I ask. I'll address some of the things he said about my own case in another thread.

1) Why are some colds I've gotten since being on rtx ridiculously short in duration (eg 36 hrs)?
Most of the symptoms from a cold are due to the immune system's reaction, as it mounts a huge effort to get ride of the virus. With a weaker immune system you don't get the big reaction.

2) Why did they use 1,000 mg solumedrol per rtx infusion in the RAVE trial, but they use less now?
When they began using rtx for Wegs in 2003, they had no idea how it would behave. They were totally in the dark. They used the highest dose of solumedrol possible to prevent allergic reaction. As they've used rtx more, they've found that they can get away with less.

3) Why do some docs do the rtx infusions without any solumedrol?
Because not everyone will have an anaphylactic reaction to the rtx. However, many people will have a reaction and when it happens it's very bad. It's risky not to use any solumedrol. Also, if they do have a reaction they might not be able to use rtx again as the body has figured out that it's a foreign substance. He would not give rtx without solumedrol.

4) Why do some people require 4 infusions of rtx instead of 2 (ie, 2 infusions don't get the Wegs under control)?
He believes this happens more often with "larger" people. The dose of the 2 infusions is not weight-based but the dose for the 4 infusions is. Also, he's noticed that larger people seem to need the once-a-week dosing. (This confirmed my hypothesis. Score 1 for Sangye. :biggrin1:)

5) The RAVE trial used the 4-infusion protocol, so where did the 2-infusion protocol come from?
Every other AI disease that is treated with rtx uses a 2-infusion protocol. When they tried this with Weggies in their clinics (ie, not in studies) it seemed to work just as well as 4 infusions for many people. It's less rtx, which means less exposure to the drug-- a good thing.

I'll post the rest in a second segment...

[Sangye]

We talked about rtx in much more depth than usual:

1) Since rtx always destroys the B cells, why doesn't it always work to control Wegs?
About 70% of people respond to rtx. That's on par with other drugs. The thing is, only about 10% of the body's B cells are in circulation, where rtx can find them. That means 90% of the body's B cells are in tissues (eg, bone marrow, joint fluid) and are therefore "hidden" from rtx. It could be that those hidden B cells are the trouble-makers-- to a greater or lesser extent in various people.

This hidden population of B cells also explains why symptoms can return before the B cells return.

2) How is it that some people have one round of rtx and go into lasting remission?
Prolonged remission happens in about 25% of people. The other 75% deal with recurring disease regardless of which drug they've been on.

3) For people treated with rtx, why doesn't Wegs flare as soon as the B cells return?
We don't know. There are so many types of Wegs activity-- severe, moderate, minimal (he called them "Wegs Lite" LOL), or maybe the person has borderline Wegs (ie, the body hasn't fully developed the disease).

Dr Seo said some things about Wegs and rtx that were very surprising:
No one really knows exactly how rtx works to control Wegs. Yes, we know that rtx targets the CD20 receptor on B cells and kills the B cell, but we don't know how that controls Wegs. In fact, they don't fully understand the mechanism of Wegs itself! They used to think T cells were the issue with Wegs, not B cells.

He said it all makes for a good story-- bad B cells produce antibodies that attack the blood vessels, rtx kills those B cells and the Wegs gets under control-- but there are huge chunks missing from the story. So they are really still in the dark about Wegs, much less rtx. I thought this was fascinating.

[me2]

Thank you Sangye for asking the questions and giving us this great summation. Very interesting. My doc is doing something with me that I had not heard of before. He told me tha a 'a guy in England ' has been having good results with a single dose of 1000 mg of rtx at six months to maintain remission. I asked if it was Dr Jayne and he didin't know. Apparently this info is not from a trial but from someones practice.
Now I guess I will become part of his practice.
I asked what the down side was to giving more and he said "Well, somebody had to pay for it for one thing". I hope he was being a bit flip
because where my central health is concerned , paying for it is not an option to worry about. I assume tha it also reduces risk from exposure to rtx. I get the sense my doc is somewhat leary of it. He is cautious with new treatments that have not a long track record.
I appreciate that sort of caution.
So in September I will get my rtx 'booster shot'. I will be interested how it makes me feel. Its not THAT far away. My health has been imroving on rtx, reducing prednisone (yay. Down to 30 mg for first time in a long time. Not exactly low but not 60 mg either and HEADED in the right direction for a change. And taking low dose methotrexate.)

Very interesting the science and the gaps in science we are dealing with here. Thanks again for the report. I hope you are doing well.
We need to get you back into the general population as well as my self. Its been 12 years of battle for me and I am feeling myself inching back towards a more mormal life. I hope the same for others here.
After such a long period I want to add that my work with my 'shrink' and my dreams has been extremely helpful with this process. Its not that easy. To quote a song "I've been too long in the wasteland".

[Sangye]

That's very interesting, me2. Dr Seo is also very cautious about rtx. At every visit he reiterates that the thought of me using it for the next 10 years (at least) is worrisome due to my "young" age (47). I hope the one dose of rtx works for you. I'm so happy that you're improving!

When I began therapy my therapist said it would be hard work and I'd have to go through some pretty dark days for awhile. She sure was right. Glad your therapy is helping you so much. :smile1:

[Brooke]

Thank you Sangye for the wonderful information! I think I will bring a few of these questions to my doc at Mayo and see what she has to say as well :)
I'm pretty curious to why I didn't have the solumedrol each infusion. Just the first infusion for each round. Sounds like we need it in case of a reaction.

[Sangye]

As much as I can't stand solumedrol, I wouldn't want to lower the dose or stop using it during the infusions. I've watched more than one person go into anaphylactic shock during infusions for other drugs. It's terrifying.

[freakyschizogirl]

No one really knows exactly how rtx works to control Wegs. Yes, we know that rtx targets the CD20 receptor on B cells and kills the B cell, but we don't know how that controls Wegs. In fact, they don't fully understand the mechanism of Wegs itself! They used to think T cells were the issue with Wegs, not B cells.

He said it all makes for a good story-- bad B cells produce antibodies that attack the blood vessels, rtx kills those B cells and the Wegs gets under control-- but there are huge chunks missing from the story. So they are really still in the dark about Wegs, much less rtx. I thought this was fascinating.

Wow, this is all very interesting for me as someone about to start out on RTX.

Solumedrol - Why dont you like it Sangye?? And this wasn't mentioned at my last visit to Addenbrooke's maybe they'll talk about it nearer the infusion date. And they also said that it was very rare for people to have a reaction to RTX...hmmm.

Why dont they base the 2 infusions on weight but they do with the 4? This concerns me as a larger person. It was mentioned that they would look to getting my weight down after i come off MTX and Pred. As for me i cant wait to get off the stinking Pred.

Thanks for asking Dr Seo Sangye, what a guy.

[Sangye]

Solumedrol is super high dose pred. The 100mg of solumedrol I get with each rtx infusion is equivalent to 155 mg pred. I've never--not even on 1,000mg solumedrol-- gotten the increase in energy from pred. It's always made me much weaker. So the big hits are really bad.

Even if you get solumedrol before an infusion, you can still have a reaction to rtx. THAT is very rare but possible. Dr Seo said not everyone will have a reaction to rtx if no solumedrol is given, but the risk is too high.

I have no idea why they don't base the 2 infusions on weight. Wish I'd asked.

[pberggren1]

Thank you Sangye.

This is all very interesting. My doc also told me a while back that they know very little of the actual mechanisms of Wegs and how rtx controls Wegs.

[Brooke]

That is just crazy, I am going to for sure ask my doc why the solumedrol was only used during the first infusion both times. I wonder how long it stays in our systems?

[Sangye]

I would love to know the reason for that, Brooke. You're getting treated at Mayo, aren't you?

[Brooke]

Lol, yes I am, Dr. Karina Keogh in the Pulmonary department.
Her secretary did say she is a Wegeners specialist/expert... Are there actual Wegener's Experts?
I do like her a lot and so far she has helped me a great deal so I trust her.
I see her in August, should I personally ask her if she is a Wegener's Expert?

[freakyschizogirl]

:thumbdn:Big thumbs down from me regarding the high dose Solumedrol...My mum recently had a bit hit of prednisolone and it did her no good, like you Sangye it made her feel worse, not better.

Brooke, I wonder if any doctor can actually be called a Wegeners expert as its so wide ranging and varied from person to person.

[Sangye]

The purpose of the solumedrol with rtx isn't to make you feel good, it's to prevent an allergic reaction.

Yes, there are Wegs specialists. I assume Dr Keogh is, but I'm not sure. Ask her if she specializes in treating Wegs.

[drz]

Lol, yes I am, Dr. Karina Keogh in the Pulmonary department.
Her secretary did say she is a Wegeners specialist/expert... Are there actual Wegener's Experts?

I see her in August, should I personally ask her if she is a Wegener's Expert?

I am unaware of recognized credentialing organization that certifies any doctor as an expert in treating GPA. They should be board certified in their specialty such as rheumatology or nephrology or their field. They should list vasculitis as one of their clinical interests. The key might be how many patients have they treated, how many are they currently treating, and how much education have they had in treating this illness by attending symposiums and conferences. The doctors listed at the Vasculitis Foundation indicate they are interested in treating Vasculitis and feel comfortable enough to consult with other doctors that wish to have a consult but I suspect many "experts" do not choose to be listed there.

A good general question is to ask about their experience in treating GPA patients and their general philosophy about treatment and then to decide if you are comfortable with their answers. I like to ask who would they consult if your treatment runs into a snag. When they tell me they have consulted with Specks, Merkel and Falk I feel reassured.

[Sangye]

The other factor I'd look for is a doctor who is actively involved in Wegs research.

[Jack]

Agree with Sangye.
I have Googled all mine against Wegener's and checked out the research papers they have written or that their work is mentioned in. I'm lucky enough to be close to a Vasculitis research group in a teaching hospital so there are several consultants who are leaders in the field.

[drz]

The other factor I'd look for is a doctor who is actively involved in Wegs research.

I think a good doctor could keep up with the research in the field without being any active researcher. Some researchers are also great clinicians but some researchers may develop a pet theory they want to prove and not be as open to all the research findings or lack the personality traits to be a good clinician. Some doctors do not do well working with live or awake patients who ask questions and may specialize in reading x-rays or studying tissue samples.

[pberggren1]

I think a good doctor could keep up with the research in the field without being any active researcher. Some researchers are also great clinicians but some researchers may develop a pet theory they want to prove and not be as open to all the research findings or lack the personality traits to be a good clinician. Some doctors do not do well working with live or awake patients who ask questions and may specialize in reading x-rays or studying tissue samples.

I find this post rather funny.

[Sangye]

drz, Easily 90% of the questions I ask Dr Seo could only be answered by someone immersed in the research. They have "insider" access to ongoing and upcoming research as well. Someone who is only relying on published research wouldn't know which drugs are coming down the pike, or problems the major centers are having, etc....

Having said that, it's great if a non-Wegs specialist keeps up with all the research. I give them tons of credit for doing that.

[GARYfromBOSTON]

Great info in this thread! Very nice of you to gather questions to bring to your doc. My doctor has also told me RTX only destroys B cells in the blood stream and that some are left in bone marrow. I had no idea only 10% were destroyed!

[Sangye]

Yeah, for some reason I had the percentages reversed in my mind, thinking 10% were in tissues and 90% were in circulation. It's been a long time since I took those courses!

[Sangye]

ROTFL http://www.smileyhut.com/laughing/rofl.gif (http://www.smileyhut.com) Gary, did you just add that signature about getting a Wegs specialist or it would upset Sangye? Hilarious, and also embarrassingly true!

[jola57]

Great ROTFL Sangye

[GARYfromBOSTON]

I added last year. I had not been around for a while :(