Clinical trial: effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study

• Published in: Journal of gastroenterology Vol. 46; no. 1; pp. 46 - 56
• Main Authors: Hiwatashi, Nobuo, Suzuki, Yasuo, Mitsuyama, Keiichi, Munakata, Akihiro, Hibi, Toshifumi
• Format: Journal Article
• Language: English
• Published: Japan Japan : Springer Japan 01.01.2011; Springer Japan; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Clinical trials; Colitis, Ulcerative - drug therapy; Colorectal Surgery; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Gastroenterology; Hepatology; Humans; Male; Medicine; Medicine & Public Health; Mesalamine; Mesalamine - administration & dosage; Mesalamine - adverse effects; Mesalazine; Middle Aged; Original Article—Alimentary Tract; Phase III randomized study; Severity of Illness Index; Surgical Oncology; Tablets; Treatment Outcome; UC-DAI score; Ulcerative colitis; Young Adult; UC-DAI score; Mesalazine; Phase III randomized study; Ulcerative colitis
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-010-0308-3

Background and aims Oral mesalazine formulations are effective in the treatment of active ulcerative colitis (UC). It is not clear what induction dose of mesalazine is optimal for treating patients with active UC. We aimed to evaluate the efficacy and safety of 4 versus 2.25 g/day for selected patients with active UC. Methods A multicenter, randomized, double-blind, parallel-group clinical study in 39 Japanese medical institutions. A total of 123 patients with moderately active UC received 4 g/day (two divided doses) versus 2.25 g/day (three divided doses) for 8 weeks. Primary endpoint was the ulcerative colitis-disease activity index (UC-DAI) score before and after 8 weeks of treatment. The improvement of each individual UC-DAI variable, remission, and efficacy rates were secondary endpoints. Safety was determined by laboratory data, vital signs, subjective symptoms, and objective findings. Results Patients receiving 4 g/day achieved a change in UC-DAI score significantly superior to those receiving 2.25 g/day [−3.0 (95% confidence intervals (CI) −3.8 to −2.3) vs. −0.8 (95% CI −1.8 to 0.1), respectively]. There were significant differences in all UC-DAI variables between the groups. Remission rates were 22.0% (4 g/day) and 15.3% (2.25 g/day). The efficacy rate was significantly better with 4 versus 2.25 g/day [76.3 vs. 45.8%, respectively (95% CI 13.8-47.2); P = 0.001]. No difference was seen in adverse events or adverse drug reactions. Conclusions A dose of 4 g/day was significantly superior to 2.25 g/day in terms of UC-DAI score for patients with moderately active UC. Safety profiles were similar for both doses.