High dose ursodeoxycholic acid in primary sclerosing cholangitis does not prevent colorectal neoplasia

Aliment Pharmacol Ther. 2012 Feb;35(4):451-7. doi: 10.1111/j.1365-2036.2011.04966.x. Epub 2012 Jan 5.

Abstract

Background: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) have a high risk of developing colorectal cancer and dysplasia. Ursodeoxycholic acid (UDCA) has been suggested to have chemopreventive effects on the development of colorectal cancer and dysplasia but long-term data and larger trials are lacking.

Aim: To evaluate the effect of high dose (17-23 mg/kg/day) UDCA on colorectal neoplasia in a cohort of patients with PSC and IBD.

Methods: From our previous 5-year randomised controlled trial of UDCA vs. placebo in PSC, we performed a follow-up of 98 patients with concomitant IBD from entry of the trial 1996-1997 until 2009 for development of colorectal cancer or dysplasia.

Results: The total follow-up time was 760 person-years. Dysplasia/cancer-free survival was compared between placebo- (n = 50) and UDCA-treated (n = 48) patients. There was a similar frequency of dysplasia or cancer after 5 years between patients originally assigned to UDCA or placebo (13% vs. 16%) and no difference in dysplasia/cancer-free survival (P = 0.46, log rank test). At the end of 2009 no difference in cancer-free survival was detected, 30% of the placebo patients compared with 27% of UDCA patients had developed colorectal cancer or dysplasia.

Conclusions: Long-term high dose ursodeoxycholic acid does not prevent colorectal cancer or dysplasia in patients with primary sclerosing cholangitis-associated inflammatory bowel disease.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cholagogues and Choleretics / administration & dosage*
  • Cholangitis, Sclerosing / complications
  • Cholangitis, Sclerosing / drug therapy*
  • Cohort Studies
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / prevention & control*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Sweden
  • Ursodeoxycholic Acid / administration & dosage*
  • Young Adult

Substances

  • Cholagogues and Choleretics
  • Ursodeoxycholic Acid