Re:Dr. Lindor, Dr. Chapman and the Urso question.

[Guest guest]

We had our PSC-Support UK meeting, in Oxford on Saturday; I'm preparing a report on this for our newsletter. The following includes Dr. Chapman's response to the Mayo High-dose Urso trial results.

The trial which has been progressing for the last 5 years was abruptly halted when it was found that Urso was harmful to the Urso group resulting in 3 times the expected number of patients with varices. The placebo group who didn't take Urso also did badly. A number of patients went on to transplantation. Dr. Lindor stopped prescribing Urso.

Something clearly went very wrong here. According to our judgenent (in the UK), some of these patients were very ill (before the trial). This may have skewed the results and there may have been a big element of chance. The results go completely against the results of trials and experience in the UK, Scandinavia

and Germany as well as previous trials and experience at the Mayo. Dr. Chapman's information is that the Mayo has resumed giving moderate doses of Urso to PSC patients.

With every drug there's an optimal level, (although this may vary between patients), After that there can be some toxicity at higher doses. It may be suspected that the dose used at the Mayo was toxic. From absorption studies the dose should be 20-25mg/kilo bodyweight per day. It is not true to say that the Mayo has abandoned Urso and the anticancer effects in mild to moderate doses means we should certainly not stop patients having Urso. Over many year we have simply not had any problems with Urso and our cancer and transplantation rates are extremely low. (Dr. Chapman has around 200 PSC patients in his clinic.)

In the light of this result we will get together our uncontrolled results for publication. Dr. C. said that Falk Pharma, who make Ursofalk in Europe were also very puzzled.

A Question was put to him as to what sense it makes to include a large number of quite ill patients in an Urso trial.

Presumably these patients were in Endstage liver disease with cirrhotic livers and severely damaged bile ducts. Urso wouldn't be likely to help such patients. Dr. C. agreed that that was an important question.

Ivor (PSC-Support, UK)

[Guest guest]

We had our PSC-Support UK meeting, in Oxford on Saturday; I'm preparing a report on this for our newsletter. The following includes Dr. Chapman's response to the Mayo High-dose Urso trial results.

The trial which has been progressing for the last 5 years was abruptly halted when it was found that Urso was harmful to the Urso group resulting in 3 times the expected number of patients with varices. The placebo group who didn't take Urso also did badly. A number of patients went on to transplantation. Dr. Lindor stopped prescribing Urso.

Something clearly went very wrong here. According to our judgenent (in the UK), some of these patients were very ill (before the trial). This may have skewed the results and there may have been a big element of chance. The results go completely against the results of trials and experience in the UK, Scandinavia

and Germany as well as previous trials and experience at the Mayo. Dr. Chapman's information is that the Mayo has resumed giving moderate doses of Urso to PSC patients.

With every drug there's an optimal level, (although this may vary between patients), After that there can be some toxicity at higher doses. It may be suspected that the dose used at the Mayo was toxic. From absorption studies the dose should be 20-25mg/kilo bodyweight per day. It is not true to say that the Mayo has abandoned Urso and the anticancer effects in mild to moderate doses means we should certainly not stop patients having Urso. Over many year we have simply not had any problems with Urso and our cancer and transplantation rates are extremely low. (Dr. Chapman has around 200 PSC patients in his clinic.)

In the light of this result we will get together our uncontrolled results for publication. Dr. C. said that Falk Pharma, who make Ursofalk in Europe were also very puzzled.

A Question was put to him as to what sense it makes to include a large number of quite ill patients in an Urso trial.

Presumably these patients were in Endstage liver disease with cirrhotic livers and severely damaged bile ducts. Urso wouldn't be likely to help such patients. Dr. C. agreed that that was an important question.

Ivor (PSC-Support, UK)

[Guest guest]

Lori,

I also attended the UK PSC Support meeting. What I think Dr. Chapman

said is that the quantities given in the Mayo clinic trial were too

high in his opinion. The Mayo clinic chose for a 30-35 mg/kg

bodyweight/day of UDCA. Dr Chapman thinks that 20-25 mg/kg

bodyweight/day of UDCA is the correct dose and that taking it in higher

dosage can have had adverse effects on patients in the trial, especialy

with those patients that were in end stage liver disease already (Dr.

Chapman thought it was a mistake to include these in the trial in the

first place).

I would like to thank Ivor and the rest of the people with the Uk

support group for their warm welcome and setting an example of how a

support group should work. I hope I will be able to create something

like it in Israel.

Regards,

Chaim Boermeester, Israel

[Guest guest]

Thanks for that info, that makes lots of sense and very interesting. It does not make sense to me to include people much farther advanced with PSC in the study. Everyone taking part in the study or at least one study should have been in a similar condition but I am not a doc.

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

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www.Lori.FirstWeber.com

Re:Dr. Lindor, Dr. Chapman and the Urso question.

Lori,I also attended the UK PSC Support meeting. What I think Dr. Chapman said is that the quantities given in the Mayo clinic trial were too high in his opinion. The Mayo clinic chose for a 30-35 mg/kg bodyweight/day of UDCA. Dr Chapman thinks that 20-25 mg/kg bodyweight/day of UDCA is the correct dose and that taking it in higher dosage can have had adverse effects on patients in the trial, especialy with those patients that were in end stage liver disease already (Dr. Chapman thought it was a mistake to include these in the trial in the first place).I would like to thank Ivor and the rest of the people with the Uk support group for their warm welcome and setting an example of how a support group should work. I hope I will be able to create something like it in Israel.Regards,Chaim Boermeester, Israel

[Guest guest]

-----Original

Message-----

Anyone know what they mean by the statement? It may be suspected that the dose used at the

Mayo was toxic.

Try this (it’s kind

of long, but describes toxic perfectly).

http://en.wikipedia.org/wiki/Toxicity

Barb in Texas - Together in the Fight.... Whatever it

Takes!

__

[Guest guest]

Hello everyone - fantastic forum. apologies if my post does not look

right, I am new to using this forum and am officially de-lurking

<>

I was also at the UK PSC Suport Group meeting in Oxford. Hello to

Ivor and Chaim who I see have posted on this thread.

I would like to add to the information on this thread about the URSO

trial and what Dr Chapman said:

First, Dr Chapman was very careful to qualify his statements by

saying that we would all have to wait to see the full paper on the

URSO trial before we can make conclusions, however it was his

understanding that the patients on high dose Urso required liver

transplant more rapidly.

Dr Chapman said that no one was suggesting that Urso should be

stopped especially in light of its chemo-prreventative benifits. Dr

Chapman himself has found that Urso is well-tolerated even in recent

studies, so was staggered by the Mayo results.

Regarding people's comments about the fact that there maybe was a

problem with the research sample: From my own point of view, I assume

Mayo clinic used controlled groups (eg high dose group with end stage

liver disease and low/moderate/no dose groups of similar staged

patients). It seems (from the limited information we currently have,

and we don't know if the group differences were significant or down

to chance) that the result is saying that there *may* be no benefit

of Urso to patients with end stage liver disease? Surely this is a

valid result that we would want to know. I wonder if they are able to

see from their results at what point the benefit ceases?

I am itching (no pun intended)to read the full research report once

it is published.

e Walmlsey

[Apologies if I am repeating myself here but I read this thread and

was compelled to reply immediately]

[Guest guest]

Hello everyone - fantastic forum. apologies if my post does not look

right, I am new to using this forum and am officially de-lurking

<>

I was also at the UK PSC Suport Group meeting in Oxford. Hello to

Ivor and Chaim who I see have posted on this thread.

I would like to add to the information on this thread about the URSO

trial and what Dr Chapman said:

First, Dr Chapman was very careful to qualify his statements by

saying that we would all have to wait to see the full paper on the

URSO trial before we can make conclusions, however it was his

understanding that the patients on high dose Urso required liver

transplant more rapidly.

Dr Chapman said that no one was suggesting that Urso should be

stopped especially in light of its chemo-prreventative benifits. Dr

Chapman himself has found that Urso is well-tolerated even in recent

studies, so was staggered by the Mayo results.

Regarding people's comments about the fact that there maybe was a

problem with the research sample: From my own point of view, I assume

Mayo clinic used controlled groups (eg high dose group with end stage

liver disease and low/moderate/no dose groups of similar staged

patients). It seems (from the limited information we currently have,

and we don't know if the group differences were significant or down

to chance) that the result is saying that there *may* be no benefit

of Urso to patients with end stage liver disease? Surely this is a

valid result that we would want to know. I wonder if they are able to

see from their results at what point the benefit ceases?

I am itching (no pun intended)to read the full research report once

it is published.

e Walmlsey

[Apologies if I am repeating myself here but I read this thread and

was compelled to reply immediately]

[Guest guest]

Thanks so much for your thoughtful comments. And I hope your "itching" for results isn't extremely irritating! Thanks again.

Joanne H

(, Ca., mom of , 18, UC/PSC 2-06; JRA 98)

Hello everyone - fantastic forum. apologies if my post does not look right, I am new to using this forum and am officially de-lurking <<big wave>>e Walmlsey[

..

[Guest guest]

Can anyone tell me what the dose should be based on Dr. Lindors advise for a 130 pound boy (his weight is way up because of the steroids) . I do not get the whole kilos etc. but I am afraid he is on a high dose because he takes 1000 mg's a day..

At Your Service,

Stevie Lynn Gedgaudas

Customer Care Manager

Apple Vacations

101 Northwest Point Blvd.

Elk Grove Village, IL 60007

sgedgaud@...

[Guest guest]

Stevie,One pound equals .45359237 kg.So 130 X .4535 = 58.95 kgIf the dose you want is 20mg to 25 mg then just multiply58.95 X 20 =1,179mg or58.95X 25 = 1,473 mgSo your son at 1,000 mg is at a 17mg per kg/bw dose.Does that make sense? I'm sure someone will correct me if I did that wrong.LeeCan anyone tell me what the dose should be based on Dr. Lindors advise for a 130 pound boy (his weight is way up because of the steroids) . I do not get the whole kilos etc. but I am afraid he is on a high dose because he takes 1000 mg's a day..

[Guest guest]

Stevie,One pound equals .45359237 kg.So 130 X .4535 = 58.95 kgIf the dose you want is 20mg to 25 mg then just multiply58.95 X 20 =1,179mg or58.95X 25 = 1,473 mgSo your son at 1,000 mg is at a 17mg per kg/bw dose.Does that make sense? I'm sure someone will correct me if I did that wrong.LeeCan anyone tell me what the dose should be based on Dr. Lindors advise for a 130 pound boy (his weight is way up because of the steroids) . I do not get the whole kilos etc. but I am afraid he is on a high dose because he takes 1000 mg's a day..

[Guest guest]

-----Original

Message-----

Can anyone tell me what the dose should be based on Dr. Lindors

advise for a 130 pound boy (his weight is way up because of the steroids) .

I’m kind of worried (maybe leery is a better word) about

your question and any answers you may receive. Dr. Lindor hasn’t advised us. We’re all jumping the gun here and

discussing the results of his study before he even writes his report. Discussion is a good thing, but we have

to wait and see what his reports says before we talk

to our doctors about the dose we’re on. Your son is a boy, so what may be right

for an adult, might actually harm a child. Plus as you say his weight (because of

steroids) is a factor too. I guess what

I’m trying to say is, please wait and talk to

your son’s doctor before you do anything. It’s the only way to be sure of the

dose your son should or shouldn’t take. Hope this makes sense, I’d hate for

anyone to do anything that might harm someone just because we’ve been

discussing it here. As much as we like

to think we know, none of us are doctors and we just don’t know the

reasoning behind his stopping the study.

Barb in

Texas - Together in the Fight.... Whatever it

Takes!

[Guest guest]

Thanks Barb, these are all good points and I should also have made them when I answered her question.Lee-----Original Message-----Can anyone tell me what the dose should be based on Dr. Lindors advise for a 130 pound boy (his weight is way up because of the steroids) . I’m kind of worried (maybe leery is a better word) about your question and any answers you may receive. Dr. Lindor hasn’t advised us. We’re all jumping the gun here and discussing the results of his study before he even writes his report. Discussion is a good thing, but we have to wait and see what his reports says before we talk to our doctors about the dose we’re on. Your son is a boy, so what may be right for an adult, might actually harm a child. Plus as you say his weight (because of steroids) is a factor too. I guess what I’m trying to say is, please wait and talk to your son’s doctor before you do anything. It’s the only way to be sure of the dose your son should or shouldn’t take. Hope this makes sense, I’d hate for anyone to do anything that might harm someone just because we’ve been discussing it here. As much as we like to think we know, none of us are doctors and we just don’t know the reasoning behind his stopping the study.

[Guest guest]

Thanks Barb, these are all good points and I should also have made them when I answered her question.Lee-----Original Message-----Can anyone tell me what the dose should be based on Dr. Lindors advise for a 130 pound boy (his weight is way up because of the steroids) . I’m kind of worried (maybe leery is a better word) about your question and any answers you may receive. Dr. Lindor hasn’t advised us. We’re all jumping the gun here and discussing the results of his study before he even writes his report. Discussion is a good thing, but we have to wait and see what his reports says before we talk to our doctors about the dose we’re on. Your son is a boy, so what may be right for an adult, might actually harm a child. Plus as you say his weight (because of steroids) is a factor too. I guess what I’m trying to say is, please wait and talk to your son’s doctor before you do anything. It’s the only way to be sure of the dose your son should or shouldn’t take. Hope this makes sense, I’d hate for anyone to do anything that might harm someone just because we’ve been discussing it here. As much as we like to think we know, none of us are doctors and we just don’t know the reasoning behind his stopping the study.

[Guest guest]

Thanks Barb, these are all good points and I should also have made them when I answered her question.Lee-----Original Message-----Can anyone tell me what the dose should be based on Dr. Lindors advise for a 130 pound boy (his weight is way up because of the steroids) . I’m kind of worried (maybe leery is a better word) about your question and any answers you may receive. Dr. Lindor hasn’t advised us. We’re all jumping the gun here and discussing the results of his study before he even writes his report. Discussion is a good thing, but we have to wait and see what his reports says before we talk to our doctors about the dose we’re on. Your son is a boy, so what may be right for an adult, might actually harm a child. Plus as you say his weight (because of steroids) is a factor too. I guess what I’m trying to say is, please wait and talk to your son’s doctor before you do anything. It’s the only way to be sure of the dose your son should or shouldn’t take. Hope this makes sense, I’d hate for anyone to do anything that might harm someone just because we’ve been discussing it here. As much as we like to think we know, none of us are doctors and we just don’t know the reasoning behind his stopping the study.

[Guest guest]

The problem is that there would be only a few people in the research.

Not many people with PSC are in similar conditions....

Chaim Boermeester, Israel

>

> Thanks for that info, that makes lots of sense and very

interesting.  It does not make sense to me to include people much

farther advanced with PSC in the study.  Everyone taking part in the

study or at least one study should have been in a similar condition but

I am not a doc.

>

>  

> Lori A.

>