Guest guest Posted November 5, 2008 Report Share Posted November 5, 2008 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 Quote Link to comment Share on other sites More sharing options...
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