Comparison of efficacy of once daily multimatrix mesalazine 2.4 g/day and 4.8 g/day with other 5-aminosalicylic acid preparation in active ulcerative colitis: a randomized, double-blind study

Abstract

Background/AimsThis study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day.MethodsIn this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score.ResultsThe mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety.ConclusionsThis study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.

Is once daily multimatrix mesalazine therapy effective regardless of the dose in patients with mild to moderate ulcerative colitis?

“…These results of the study by Ogata et al 6 were similar to that of a recent meta-analysis. 7 The meta-analysis demonstrated that 50% of patients who received 5-ASA failed to achieve remission compared to 52% of patients who received 5-ASA comparator (RR, 0.94; 95% CI, 0.86–1.02).…”

“…Unlike the study by Ogata et al, 6 the meta-analysis did not assess the significant difference in efficacy between the two 5-ASA dosing regimens (4.8 g/day vs. 2.4 g/day), including pH-release and MMX mesalazines. 7 However, similar to the present study, 6 subgroup analysis of several studies demonstrated that patients with moderate UC might benefit from the high dose of mesalazine (4.8 g/day). 7 8 9 This indicates that the severity of disease can be a factor that affects the response to 5-ASA treatment.…”

“… 9 However, in those patients transferred directly from prior low-dose 5-ASA, MMX mesalazine 4.8 g/day was superior to placebo, while its efficacy over placebo in patients transferred directly to MMX mesalazine 2.4 g/day was not significantly different. Ogata et al 6 also reported that MMX-4.8 g/day had more beneficial than 2.4 g/day because more than 80% patients were directly transferred from prior low-dose 5-ASA. This suggested that the non-responders to low-dose 5-ASA might respond to escalation in the dose of MMX mesalazine.…”

“…In the current issue of Intestinal Research , Ogata et al 6 investigated the efficacy and safety of 2 doses of MMX mesalazine (2.4 [MMX-2.4 group] and 4.8 g/day [MMX-4.8 group]) compared with controlled-release mesalazine 2.25 g/day (thrice daily, controlled-2.25 group). Patients were randomly assigned either to MMX-2.4 (n=85), MMX-4.8 (n=81), or controlled-2.25 group (n=85) for 8 weeks.…”

Switching between Three Types of Mesalazine Formulation and Sulfasalazine in Patients with Active Ulcerative Colitis Who Have Already Received High-Dose Treatment with These Agents

“…However, studies with fair comparisons are scarce because the doses of comparative mesalazine formulations are sometimes different (e.g., 2.25 g/day of Pentasa vs. 3.6 g/day of Asacol). Notably, in the few studies using similar doses of different types of mesalazine formulation (3 g/day of pH-dependent mesalazine vs. 3 g/day of time-dependent mesalazine [9] and 2.4 g/day of MMX mesalazine vs. 2.25 g/day of time-dependent mesalazine [10]), an equivalent efficacy and safety were observed in mild to moderately active UC patients.…”