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

P>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 (Clinicaltrials.gov: NCT00577473, NCT00073021).