Randomised clinical trial: once- vs. twice-daily prolonged-release mesalazine for active ulcerative colitis

Background Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient. Aim To compare the efficacy and safety of once- (OD) vs. twice- (BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study. Methods Eligible patients (n=206) were randomised to 8weeks of mesalazine (4g/day), either OD with two sachets of 2g mesalazine granules in the morning (n=102) or BD with one 2g sachet in the morning and one in the evening (n=104). Patients also received 4weeks of mesalazine enema 1g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index (UC-DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8weeks. Patients recorded stool frequency and rectal bleeding in a daily diary. Results The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval 3.4, 24.1; P=0.14). Improvement of UC-DAI score (92% vs. 79%; P=0.01) and mucosal healing (87.5% vs. 71.1%; P=0.007) were significantly better, time to remission significantly shorter (26 vs. 28days; P=0.04) and safety similar with OD vs. BD dosing. Conclusions When combined with mesalazine enema, prolonged-release mesalazine once-daily 4g is as effective and well tolerated as 2g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789).