STUDY ** High-Dose Ursodeoxycholic Acid Fails in PSC**

[Guest guest]

Interesting. I was taken off URSO about 2-3 weeks ago, based on what Dr. Gores said in his e-mail to me. My doctor agreed to take me off the URSO. Things went very quickly south, and my pouchitis acted up, the nausea went to vomiting and the inability to take my meds; together with the vomiting and diarrhea I quickly dehydrated and was hospitalized 3 times in the last 2 weeks. I'm back on Ursodiol now, but at intermediate levels.Marie

To: From: barbhenshaw@...Date: Wed, 5 Nov 2008 20:56:16 -0600Subject: STUDY ** High-Dose Ursodeoxycholic Acid Fails in PSC**

In patients with PSC, treatment with high-dose

ursodeoxycholic acid (UDCA) may cause more harm than good, according to a study

reported here.

Consistent

with anecdotal reports, UDCA improved liver biochemistry, but did not improve

survival and was associated with twice as many serious adverse events as

placebo, said Lindor, M.D., of the Mayo Clinic in Rochester, Minn.

"It led to biochemical

improvement. The unanticipated finding was an excess

of adverse events, clinically significant adverse events. That

was really surprising to us."

To

confirm the benefits observed in small uncontrolled studies, investigators

enrolled 150 patients with PSC in a randomized clinical trial.

Eligible patients had chronic cholestatic disease of at least six

months' duration, alkaline phosphatase levels more than 1.5 times normal,

cholangiographic documentation of PSC, and confirmatory liver biopsy.

The

patients were stratified by stage (I or II versus III or IV), presence or absence of varices, and Mayo risk score of less

than 1.5, or 1.5 or greater.

The

patients received UDCA 28 to 30 mg/kg/day in 250- or 500-mg Urso Forte (Axcan)

or matching placebo.

The

primary objective was to assess the effects of UDCA on the endpoints of

progression to cirrhosis, development of varices, cholangiocarcinoma,

transplant, and death.

Baseline

characteristics were similar between the two groups. About

60% of patients had stage I-II disease, and the Mayo risk score averaged 0.3 in

both groups.

Dr. Lindor reported that 52 patients in the UDCA

group and 27 in the placebo group met the endpoints, including death (four in

the UDCA group versus two with placebo), liver transplant (11 versus four), and

development of varices (15 versus five).

In a

hazards model that censored at last patient contact, the UDCA group was more

than twice as likely to meet an endpoint (HR 2.42, P=0.004). Limiting the

analysis to death or transplant, the investigators found that UDCA posed more

than twice the hazard of placebo, whether censoring was at

date off protocol (HR 2.61, P=0.046) or at last

contact (HR 2.80, P=0.028).

The

study was terminated upon the recommendation of the data safety and monitoring

Board because of futility and concern over adverse effects.

The

surprising results leave the clinical status of UDCA for PSC in limbo.

"We know that this higher dose shouldn't be used, based on this

study," Dr. Lindor said. "The intermediate

doses have not, in other studies, showed a survival benefit. They led to biochemical improvement.

"Three

studies have looked at ability of ursodeoxycholic acid to reduce colonic

dysplasia," he added. "About 70% of patients

with this liver disease have coexisting ulcerative colitis. The

risk of colon cancer with that combination is quite high.

"There are some that think the drug may have a place in reducing

that risk of cancer. The data supporting that are from

retrospective studies, and, in my mind, aren't strong enough to lead us to

recommend use on a routine basis for that indication."

FULL ARTICLE: http://www.medpagetoday.com/MeetingCoverage/AASLD/11632

Barb in

Texas - Together in the Fight - Whatever it

Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

See how Windows Mobile brings your life together—at home, work, or on the go. See Now

[Guest guest]

Interesting. I was taken off URSO about 2-3 weeks ago, based on what Dr. Gores said in his e-mail to me. My doctor agreed to take me off the URSO. Things went very quickly south, and my pouchitis acted up, the nausea went to vomiting and the inability to take my meds; together with the vomiting and diarrhea I quickly dehydrated and was hospitalized 3 times in the last 2 weeks. I'm back on Ursodiol now, but at intermediate levels.Marie

To: From: barbhenshaw@...Date: Wed, 5 Nov 2008 20:56:16 -0600Subject: STUDY ** High-Dose Ursodeoxycholic Acid Fails in PSC**

In patients with PSC, treatment with high-dose

ursodeoxycholic acid (UDCA) may cause more harm than good, according to a study

reported here.

Consistent

with anecdotal reports, UDCA improved liver biochemistry, but did not improve

survival and was associated with twice as many serious adverse events as

placebo, said Lindor, M.D., of the Mayo Clinic in Rochester, Minn.

"It led to biochemical

improvement. The unanticipated finding was an excess

of adverse events, clinically significant adverse events. That

was really surprising to us."

To

confirm the benefits observed in small uncontrolled studies, investigators

enrolled 150 patients with PSC in a randomized clinical trial.

Eligible patients had chronic cholestatic disease of at least six

months' duration, alkaline phosphatase levels more than 1.5 times normal,

cholangiographic documentation of PSC, and confirmatory liver biopsy.

The

patients were stratified by stage (I or II versus III or IV), presence or absence of varices, and Mayo risk score of less

than 1.5, or 1.5 or greater.

The

patients received UDCA 28 to 30 mg/kg/day in 250- or 500-mg Urso Forte (Axcan)

or matching placebo.

The

primary objective was to assess the effects of UDCA on the endpoints of

progression to cirrhosis, development of varices, cholangiocarcinoma,

transplant, and death.

Baseline

characteristics were similar between the two groups. About

60% of patients had stage I-II disease, and the Mayo risk score averaged 0.3 in

both groups.

Dr. Lindor reported that 52 patients in the UDCA

group and 27 in the placebo group met the endpoints, including death (four in

the UDCA group versus two with placebo), liver transplant (11 versus four), and

development of varices (15 versus five).

In a

hazards model that censored at last patient contact, the UDCA group was more

than twice as likely to meet an endpoint (HR 2.42, P=0.004). Limiting the

analysis to death or transplant, the investigators found that UDCA posed more

than twice the hazard of placebo, whether censoring was at

date off protocol (HR 2.61, P=0.046) or at last

contact (HR 2.80, P=0.028).

The

study was terminated upon the recommendation of the data safety and monitoring

Board because of futility and concern over adverse effects.

The

surprising results leave the clinical status of UDCA for PSC in limbo.

"We know that this higher dose shouldn't be used, based on this

study," Dr. Lindor said. "The intermediate

doses have not, in other studies, showed a survival benefit. They led to biochemical improvement.

"Three

studies have looked at ability of ursodeoxycholic acid to reduce colonic

dysplasia," he added. "About 70% of patients

with this liver disease have coexisting ulcerative colitis. The

risk of colon cancer with that combination is quite high.

"There are some that think the drug may have a place in reducing

that risk of cancer. The data supporting that are from

retrospective studies, and, in my mind, aren't strong enough to lead us to

recommend use on a routine basis for that indication."

FULL ARTICLE: http://www.medpagetoday.com/MeetingCoverage/AASLD/11632

Barb in

Texas - Together in the Fight - Whatever it

Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

See how Windows Mobile brings your life together—at home, work, or on the go. See Now

[Guest guest]

Interesting. I was taken off URSO about 2-3 weeks ago, based on what Dr. Gores said in his e-mail to me. My doctor agreed to take me off the URSO. Things went very quickly south, and my pouchitis acted up, the nausea went to vomiting and the inability to take my meds; together with the vomiting and diarrhea I quickly dehydrated and was hospitalized 3 times in the last 2 weeks. I'm back on Ursodiol now, but at intermediate levels.Marie

To: From: barbhenshaw@...Date: Wed, 5 Nov 2008 20:56:16 -0600Subject: STUDY ** High-Dose Ursodeoxycholic Acid Fails in PSC**

In patients with PSC, treatment with high-dose

ursodeoxycholic acid (UDCA) may cause more harm than good, according to a study

reported here.

Consistent

with anecdotal reports, UDCA improved liver biochemistry, but did not improve

survival and was associated with twice as many serious adverse events as

placebo, said Lindor, M.D., of the Mayo Clinic in Rochester, Minn.

"It led to biochemical

improvement. The unanticipated finding was an excess

of adverse events, clinically significant adverse events. That

was really surprising to us."

To

confirm the benefits observed in small uncontrolled studies, investigators

enrolled 150 patients with PSC in a randomized clinical trial.

Eligible patients had chronic cholestatic disease of at least six

months' duration, alkaline phosphatase levels more than 1.5 times normal,

cholangiographic documentation of PSC, and confirmatory liver biopsy.

The

patients were stratified by stage (I or II versus III or IV), presence or absence of varices, and Mayo risk score of less

than 1.5, or 1.5 or greater.

The

patients received UDCA 28 to 30 mg/kg/day in 250- or 500-mg Urso Forte (Axcan)

or matching placebo.

The

primary objective was to assess the effects of UDCA on the endpoints of

progression to cirrhosis, development of varices, cholangiocarcinoma,

transplant, and death.

Baseline

characteristics were similar between the two groups. About

60% of patients had stage I-II disease, and the Mayo risk score averaged 0.3 in

both groups.

Dr. Lindor reported that 52 patients in the UDCA

group and 27 in the placebo group met the endpoints, including death (four in

the UDCA group versus two with placebo), liver transplant (11 versus four), and

development of varices (15 versus five).

In a

hazards model that censored at last patient contact, the UDCA group was more

than twice as likely to meet an endpoint (HR 2.42, P=0.004). Limiting the

analysis to death or transplant, the investigators found that UDCA posed more

than twice the hazard of placebo, whether censoring was at

date off protocol (HR 2.61, P=0.046) or at last

contact (HR 2.80, P=0.028).

The

study was terminated upon the recommendation of the data safety and monitoring

Board because of futility and concern over adverse effects.

The

surprising results leave the clinical status of UDCA for PSC in limbo.

"We know that this higher dose shouldn't be used, based on this

study," Dr. Lindor said. "The intermediate

doses have not, in other studies, showed a survival benefit. They led to biochemical improvement.

"Three

studies have looked at ability of ursodeoxycholic acid to reduce colonic

dysplasia," he added. "About 70% of patients

with this liver disease have coexisting ulcerative colitis. The

risk of colon cancer with that combination is quite high.

"There are some that think the drug may have a place in reducing

that risk of cancer. The data supporting that are from

retrospective studies, and, in my mind, aren't strong enough to lead us to

recommend use on a routine basis for that indication."

FULL ARTICLE: http://www.medpagetoday.com/MeetingCoverage/AASLD/11632

Barb in

Texas - Together in the Fight - Whatever it

Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

See how Windows Mobile brings your life together—at home, work, or on the go. See Now

[Guest guest]

Well, now I can stop fretting about my 250 dose not being enough. The

more I learn, the more comfortable I am with it.

ee

>

>

> Interesting. I was taken off URSO about 2-3 weeks ago, based on

what Dr. Gores said in his e-mail to me. My doctor agreed to take me

off the URSO.

>

>

>

>

>

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>

>

>

>

>

>

>

>

>

>

>

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>

> _________________________________________________________________

> See how Windows Mobile brings your life together—at home, work, or

on the go.

> http://clk.atdmt.com/MRT/go/msnnkwxp1020093182mrt/direct/01/

>

[Guest guest]

Now that the study is out it will be interesting to see what my

doctors will recommend. I've been on low dose urso (8mg/kg/day) for

many years and did not stop taking it even after my transplants last year.

Tim R, ltx 4/4/98, 6/19/07 & 7/7/07

[Guest guest]

Now that the study is out it will be interesting to see what my

doctors will recommend. I've been on low dose urso (8mg/kg/day) for

many years and did not stop taking it even after my transplants last year.

Tim R, ltx 4/4/98, 6/19/07 & 7/7/07

[Guest guest]

-----Original

Message-----

Now that the study is out it will be interesting to see what my doctors will recommend.

Ken wasn’t on it pre-transplant (it made him sick), but after his

first rejection episode they put him on it (he doesn’t have a problem

with it now, go figure) anyway he’s on 600 mg daily!! I’ve already shot an email to his

coordinator, I’ll let y’all know what they say as soon as I hear.

Barb in Texas - Together in the Fight

- Whatever it Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

[Guest guest]

-----Original

Message-----

Now that the study is out it will be interesting to see what my doctors will recommend.

Ken wasn’t on it pre-transplant (it made him sick), but after his

first rejection episode they put him on it (he doesn’t have a problem

with it now, go figure) anyway he’s on 600 mg daily!! I’ve already shot an email to his

coordinator, I’ll let y’all know what they say as soon as I hear.

Barb in Texas - Together in the Fight

- Whatever it Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

[Guest guest]

I'm ever the optimimist, at one point on this release it actually says

that urso can " restore normal life expectancy "

http://www.medpagetoday.com/MeetingCoverage/AASLD/11632

Is this true? Are there documented cases of it combatting cirhossis

that well???

Cheers

dx PSC 08/07

[Guest guest]

I'm ever the optimimist, at one point on this release it actually says

that urso can " restore normal life expectancy "

http://www.medpagetoday.com/MeetingCoverage/AASLD/11632

Is this true? Are there documented cases of it combatting cirhossis

that well???

Cheers

dx PSC 08/07

[Guest guest]

-----Original

Message-----

anyway he’s on 600 mg daily!!

FYI, Before anyone freaks out - I know Ken’s 600mg dose = 7 to 8 per kg. My !!!! got

away from me ;-)

Barb in Texas - Together in the Fight

- Whatever it Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

[Guest guest]

-----Original

Message-----

anyway he’s on 600 mg daily!!

FYI, Before anyone freaks out - I know Ken’s 600mg dose = 7 to 8 per kg. My !!!! got

away from me ;-)

Barb in Texas - Together in the Fight

- Whatever it Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

[Guest guest]

-----Original

Message-----

anyway he’s on 600 mg daily!!

FYI, Before anyone freaks out - I know Ken’s 600mg dose = 7 to 8 per kg. My !!!! got

away from me ;-)

Barb in Texas - Together in the Fight

- Whatever it Takes!

Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007

@ Baylor/Dallas

[Guest guest]

Hee hee, I was worried for YOU lol. I am on 250 twice a day, so I was

thinking NO NO that is ok, I am on 500 a day and it is low. Glad to

see you figured it!

>

> -----Original Message-----

> anyway he's on 600 mg daily!!

>

> FYI, Before anyone freaks out - I know Ken's 600mg dose = 7 to 8 per kg.

> My !!!! got away from me ;-)

>

> Barb in Texas - Together in the Fight - Whatever it Takes!

> Son Ken (34) UC 91 PSC 99, LTX 6/21 & 6/30 2007 @ Baylor/Dallas

>

[Guest guest]

I weigh 110 and take 1000 per day. You can bet my hep

is going to get a call asking if it is really

necessary. Not just the study information, but that

drug is horrifically EXPENSIVE, and I have been on it

11 years and nothing has improved, and I never did see

a difference after starting it.

Cindy Baudoux-Northrup

[Guest guest]

I weigh 110 and take 1000 per day. You can bet my hep

is going to get a call asking if it is really

necessary. Not just the study information, but that

drug is horrifically EXPENSIVE, and I have been on it

11 years and nothing has improved, and I never did see

a difference after starting it.

Cindy Baudoux-Northrup

[Guest guest]

I weigh 110 and take 1000 per day. You can bet my hep

is going to get a call asking if it is really

necessary. Not just the study information, but that

drug is horrifically EXPENSIVE, and I have been on it

11 years and nothing has improved, and I never did see

a difference after starting it.

Cindy Baudoux-Northrup

[Guest guest]

Thanks for posting this Barb. Can anyone determine from the results

presented so far, whether the adverse effects of urso were confined to

the patients in stage IV PSC, or were spread across all stages of the

disease? I would hope that in the peer-reviewed paper they consider the

relationship between frequency of adverse effects and stage of the

disease.

Dave

(father of (23), PSC 07/03; UC 08/03)

[Guest guest]

Thanks for posting this Barb. Can anyone determine from the results

presented so far, whether the adverse effects of urso were confined to

the patients in stage IV PSC, or were spread across all stages of the

disease? I would hope that in the peer-reviewed paper they consider the

relationship between frequency of adverse effects and stage of the

disease.

Dave

(father of (23), PSC 07/03; UC 08/03)

[Guest guest]

Thanks for posting this Barb. Can anyone determine from the results

presented so far, whether the adverse effects of urso were confined to

the patients in stage IV PSC, or were spread across all stages of the

disease? I would hope that in the peer-reviewed paper they consider the

relationship between frequency of adverse effects and stage of the

disease.

Dave

(father of (23), PSC 07/03; UC 08/03)

[Guest guest]

Given the fact the article states 60% of the 150 patients were stage I

or II, while at the same time 79 patients met defined endpoints during

the study I think at least some crossover of adverse effects to Stage I

and Stage II patients has to be assumed.

In my case I was in the Stage III/IV category, was on the real

medication during the study and did not meet any of the endpoints.

Assuming there were others like me that would also support the

conclusion that at least some of the patients experiencing adverse

effects were Stage I/II.

in Seattle

>

> Thanks for posting this Barb. Can anyone determine from the results

> presented so far, whether the adverse effects of urso were confined

to

> the patients in stage IV PSC, or were spread across all stages of the

> disease? I would hope that in the peer-reviewed paper they consider

the

> relationship between frequency of adverse effects and stage of the

> disease.

>

> Dave

> (father of (23), PSC 07/03; UC 08/03)

>

[Guest guest]

Given the fact the article states 60% of the 150 patients were stage I

or II, while at the same time 79 patients met defined endpoints during

the study I think at least some crossover of adverse effects to Stage I

and Stage II patients has to be assumed.

In my case I was in the Stage III/IV category, was on the real

medication during the study and did not meet any of the endpoints.

Assuming there were others like me that would also support the

conclusion that at least some of the patients experiencing adverse

effects were Stage I/II.

in Seattle

>

> Thanks for posting this Barb. Can anyone determine from the results

> presented so far, whether the adverse effects of urso were confined

to

> the patients in stage IV PSC, or were spread across all stages of the

> disease? I would hope that in the peer-reviewed paper they consider

the

> relationship between frequency of adverse effects and stage of the

> disease.

>

> Dave

> (father of (23), PSC 07/03; UC 08/03)

>

[Guest guest]

Given the fact the article states 60% of the 150 patients were stage I

or II, while at the same time 79 patients met defined endpoints during

the study I think at least some crossover of adverse effects to Stage I

and Stage II patients has to be assumed.

In my case I was in the Stage III/IV category, was on the real

medication during the study and did not meet any of the endpoints.

Assuming there were others like me that would also support the

conclusion that at least some of the patients experiencing adverse

effects were Stage I/II.

in Seattle

>

> Thanks for posting this Barb. Can anyone determine from the results

> presented so far, whether the adverse effects of urso were confined

to

> the patients in stage IV PSC, or were spread across all stages of the

> disease? I would hope that in the peer-reviewed paper they consider

the

> relationship between frequency of adverse effects and stage of the

> disease.

>

> Dave

> (father of (23), PSC 07/03; UC 08/03)

>

[Guest guest]

I was a stage II category, and on UCDA, 1500mg/d during the study, too, and did not meet any of the the endpoints, also. The only effects i can think of, but not so sure if they can be specified as "adverse", were continous episodes of "very closely" spaced cholangitis attacks [fever, chills, nuasea----]. I was mainly sick all the time. And a high grade, intense URQ pain.Very interestingly, those cholangitis flares, did go down dramatically after stopping Urso. With regard to the pain, it did much improve right after, but i am not able to estimate how much since i was started on a continous new pain med~2mo after the stop. Whatever i was taking before was not helping the pain. Withregard to my LF's., there was a great imrovement, specially with the ALK, ALT/AST. They went a little above normal, but surprisingly, did go up again during the last couple of years, but in less amounts

than the numbers before the study.

Subject: Re: STUDY ** High-Dose Ursodeoxycholic Acid Fails in PSC**To: Date: Thursday, November 6, 2008, 5:50 PM

Given the fact the article states 60% of the 150 patients were stage I or II, while at the same time 79 patients met defined endpoints during the study I think at least some crossover of adverse effects to Stage I and Stage II patients has to be assumed.In my case I was in the Stage III/IV category, was on the real medication during the study and did not meet any of the endpoints. Assuming there were others like me that would also support the conclusion that at least some of the patients experiencing adverse effects were Stage I/II. in Seattle>> Thanks for posting this Barb. Can anyone determine from the results > presented so far, whether the adverse effects of urso were confined to > the patients

in stage IV PSC, or were spread across all stages of the > disease? I would hope that in the peer-reviewed paper they consider the > relationship between frequency of adverse effects and stage of the > disease.> > Dave > (father of (23), PSC 07/03; UC 08/03)>

[Guest guest]

I was a stage II category, and on UCDA, 1500mg/d during the study, too, and did not meet any of the the endpoints, also. The only effects i can think of, but not so sure if they can be specified as "adverse", were continous episodes of "very closely" spaced cholangitis attacks [fever, chills, nuasea----]. I was mainly sick all the time. And a high grade, intense URQ pain.Very interestingly, those cholangitis flares, did go down dramatically after stopping Urso. With regard to the pain, it did much improve right after, but i am not able to estimate how much since i was started on a continous new pain med~2mo after the stop. Whatever i was taking before was not helping the pain. Withregard to my LF's., there was a great imrovement, specially with the ALK, ALT/AST. They went a little above normal, but surprisingly, did go up again during the last couple of years, but in less amounts

than the numbers before the study.

Subject: Re: STUDY ** High-Dose Ursodeoxycholic Acid Fails in PSC**To: Date: Thursday, November 6, 2008, 5:50 PM

Given the fact the article states 60% of the 150 patients were stage I or II, while at the same time 79 patients met defined endpoints during the study I think at least some crossover of adverse effects to Stage I and Stage II patients has to be assumed.In my case I was in the Stage III/IV category, was on the real medication during the study and did not meet any of the endpoints. Assuming there were others like me that would also support the conclusion that at least some of the patients experiencing adverse effects were Stage I/II. in Seattle>> Thanks for posting this Barb. Can anyone determine from the results > presented so far, whether the adverse effects of urso were confined to > the patients

in stage IV PSC, or were spread across all stages of the > disease? I would hope that in the peer-reviewed paper they consider the > relationship between frequency of adverse effects and stage of the > disease.> > Dave > (father of (23), PSC 07/03; UC 08/03)>