High Dose URSO study

[Guest guest]

Hi ,

I understand that Mayo looks at the risk survival

model (as do many other centers), but when it comes to transplant (which means

progression to me) everyone uses MELD scores. My comments on high dose URSO refer only to finding a treatment or cure

for PSC. I’m not advocating

anyone stop taking it, in fact I have advised people not to stop taking it. Ken is taking it now.

>>Because high-dose

urso reduces AST and bilirubin and increases albumin, it is logical to suppose

that this should translate into increased survival

It may be “logical”,

but that’s not what Dr Lindor found and the study you sighted took place

in 2001. We’re several

studies beyond that – all with not even a hint of stopping progression in

PSC.

Wouldn't it be better to

maintain PSC patients on high-dose ursodiol and then look for additional

therapies which result in further improvement? This is

what is being done in primary biliary cirrhosis” :

Sure, but that’s not what’s happening, it

seems (to me at least) that the researchers have put all their eggs into the

URSO basket at the determent of PSC patients. They’ve done several studies

combining URSO with other drugs and they haven’t found anything that

works. They have been studying it for

years, it’s time to move on. I think Dr Lindor finally realized he chasing an allusive URSO dream. He knows PSC,

if he says the love affair with URSO is over, I believe him. Maybe now we can focus our attention

elsewhere and find something that actually works.

I’m positive I have a jaded view of URSO, I

ready admit that. After the study

comes out we’ll all learn more.

I just want a ~`^*_^ cure for PSC, I’m sick and

tired of it! I want someone

somewhere to find something that works and I want doctors to move on if what

their studying isn’t it. But

I do love them deeply for trying. ;-)

Barb in Texas

P.S. Here are some studies (along with the current high

dose) that probably lead Dr Lindor to give up on URSO (several of these are his

own studies.)

However, there currently are no effective medical

therapies known to halt the progression of disease. The

only definitive therapy for PSC is liver transplantation……

http://www.ncbi.nlm.nih.gov/pubmed/18449341?ordinalpos=16 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Multiple studies using standard-dosage (8-15 mg/kg/d)

and high-dosage (20-30 mg/kg/d) UDCA generally show improvement in liver

chemistries in PSC patients, and several show improvement in liver histology. However, the majority of trials using

UDCA in PSC are underpowered and fail to show improvements in clinically

relevant endpoints, such as delayed progression to cirrhosis, portal

hypertension, liver transplantation, development of cholangiocarcinoma, or death.

http://www.ncbi.nlm.nih.gov/pubmed/17335678?ordinalpos=1 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA & linkpos=2 & log$=relatedarticles & logdbfrom=pubmed

No effective medical therapy has been identified. The multiple complications of primary sclerosing

cholangitis include metabolic bone disease, dominant strictures, bacterial

cholangitis, and malignancy, particularly cholangiocarcinoma, which is the most

lethal complication of primary sclerosing cholangitis. Liver

transplantation is currently the only life-extending therapeutic alternative

for patients with end-stage disease

http://www.ncbi.nlm.nih.gov/pubmed/18528931?ordinalpos=1 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

The best-studied drug in primary sclerosing

cholangitis is ursodeoxycholic acid, which, despite a range of potentially

valuable actions on the cholestatic liver, has not yet been proved to make a

substantial impression on the course of the disease. Orthotopic

liver transplantation remains the only established long-term treatment for

primary sclerosing cholangitis.

http://www.ncbi.nlm.nih.gov/pubmed/16550044?ordinalpos=1 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA & linkpos=1 & log$=relatedarticles & logdbfrom=pubmed

UDCA therapy had no effect on delaying progression of

disease (relative risk, 0.95; 95% confidence interval, 0.38-2.36). CONCLUSION: Small-duct PSC often is recognized at an early

stage in patients with IBD; however, IBD has no impact on long-term prognosis. Although UDCA therapy improves liver biochemistries, it

may not delay disease progression during the short period of treatment.

http://www.ncbi.nlm.nih.gov/pubmed/17992695?ordinalpos=9 & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Overall, the higher-dose UDCA was well tolerated, but

results revealed no significant beneficial effects on survival or prevention of

cholangiocarcinoma in PSC. A large randomized,

controlled trial of high-dose UDCA in patients with PSC currently in progress

at the Mayo Clinic will hopefully help to address this issue more definitively. (Long article) …. http://www.medscape.com/viewarticle/569180_3

(note the words hopefully and definitively)