Randomised clinical trial: delayed-release oral mesalazine 4.8 g/day vs. 2.4 g/day in endoscopic mucosal healing--ASCEND I and II combined analysis

Aliment Pharmacol Ther. 2011 Mar;33(6):672-8. doi: 10.1111/j.1365-2036.2010.04575.x. Epub 2011 Jan 23.


Background: Recent studies have focused on the importance of mucosal healing in ulcerative colitis (UC). However, it was still unclear whether higher doses of delayed-release mesalazine (mesalamine) could provide additional benefit.

Aim: To examine how two doses of delayed-release mesalazine (4.8 g/day and 2.4 g/day) from ASCEND I and II compare in their relative ability to heal colonic mucosa over time.

Methods: Primary data from two prospective 6-week, double-blind, randomised studies in patients with mildly to moderately active UC were pooled and analysed retrospectively. The mucosal healing analysis focuses on moderately active UC patients (n=391), comprising a majority of patients (84%). Additional analyses examined the relationship between mucosal healing and dose, clinical response to therapy and patient quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ).

Results: At week 3, mucosal healing (endoscopy subscore of 0 or 1) was achieved in 65% of moderately active UC patients on 4.8 g/day and 58% of patients on 2.4 g/day (P=0.219). At week 6, this increased to 80% for 4.8 g/day and 68% for 2.4 g/day (P=0.012). Healing rates with the higher dose were also greater across all extents of disease and in patients with prior steroid use. At 6 weeks, clinical response to therapy and mucosal healing were found to be well correlated (kappa=0.694). Likewise, the change in IBDQ at week 6 showed a significant relationship with mucosal healing (P<0.0001).

Conclusion: Mucosal healing rates in UC achieved at 6 weeks were statistically significantly higher with delayed-release mesalazine at 4.8 g/day vs. 2.4 g/day.

Trial registration: ClinicalTrials.gov NCT00073021 NCT00577473.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Colitis, Ulcerative / drug therapy*
  • Colonoscopy
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Epidemiologic Methods
  • Female
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / physiology
  • Male
  • Mesalamine / administration & dosage*
  • Middle Aged
  • Quality of Life
  • Treatment Outcome
  • Wound Healing / drug effects
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Mesalamine

Associated data

  • ClinicalTrials.gov/NCT00073021
  • ClinicalTrials.gov/NCT00577473