Gastroenterology

Gastroenterology

Volume 124, Issue 4, April 2003, Pages 889-893
Gastroenterology

Clinical-Alimentary Tract
Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis,☆☆,

Presented in part at the 102nd Annual Meeting of the American Gastroenterological Association, May 20-23, 2001, Atlanta, Georgia (Gastroenterology 2001;120:A447).
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Abstract

Background & Aims: Ursodeoxycholic acid (UDCA) has shown effectiveness as a colon cancer chemopreventive agent in preclinical studies. In addition, a recent report suggests that it also may decrease the risk for developing colorectal dysplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We sought to evaluate the effect of UDCA on colorectal neoplasia in a group of patients with UC and PSC enrolled in a randomized, placebo-controlled trial. Methods: From a prior, randomized, placebo-controlled trial of UDCA therapy in PSC at our center, we followed-up patients with concomitant UC to assess the effect of UDCA on the development of colorectal dysplasia and cancer as compared with placebo. Results: Fifty-two subjects were followed-up for a total of 355 person-years. Those originally assigned to receive UDCA had a relative risk of 0.26 for developing colorectal dysplasia or cancer (95% confidence interval, 0.06-0.92; P = 0.034). Many of the patients originally assigned to the placebo group eventually received open-label UDCA. Assigning these patients to the UDCA group from the time they began active therapy did not change the magnitude of the protective effect (relative risk, 0.26; 95% confidence interval, 0.07-0.99; P = 0.049). Conclusions: UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC.

Section snippets

Materials and methods

The study protocol was reviewed and approved by the Mayo Clinic Institutional Review Board. All patients with UC from the initial PSC-UDCA trial potentially were eligible for the current study. The diagnosis of PSC was based on typical cholangiographic and liver biopsy criteria,22 and the diagnosis of UC was based on typical clinical, endoscopic, and histologic criteria. Patients with dysplasia, colon cancer, or colectomy before or within 6 months of entering the initial study were excluded. In

Results

Of the 85 patients with UC from the original study, 33 (39%) were excluded, leaving 52 patients in this follow-up study. Twenty-four patients were excluded because they were inappropriate for the present study: 17 (20%) had proctocolectomy before study entry, 5 (6%) had cancer or dysplasia diagnosed before or within 6 months of study entry, 1 diagnosis was changed to Crohn's disease, and 1 died shortly after entering the original study. Thus, only 9 patients (10% of the original cohort) who

Discussion

Our comparison of colorectal neoplasia development in PSC-UC patients entered into a randomized, placebo-controlled trial suggests a significant chemoprotective effect for UDCA in these patients, with a 74% reduction in the risk for dysplasia or cancer in those assigned to the UDCA group.

The rationale for using UDCA as a chemopreventive agent is based on in vitro and animal models and uncontrolled clinical studies. UDCA inhibits proliferation of colon cancer cell lines in vitro,15 and in rats

References (35)

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Address requests for reprints to: Darrell S. Pardi, M.D., 200 First Street SW, Rochester, Minnesota 55905. e-mail: [email protected]; fax: (507) 284-5486.

☆☆

Dr. Keith Lindor receives research funding from Axcan.

0016-5085/03/$30.00

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