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

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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