Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study

Abstract

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC.

Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI).

Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles.

Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288).

FIGURE 1

Enrolment, randomization, and follow-up of the study patients.

FIGURE 2

Proportion of remission and efficacy. The graphs show proportions of remission and efficacy in each group within 95% CIs. Each graph includes 225 patients for analyses (pH-2.4 g, 66; pH-3.6 g, 64; Time-2.25 g, 63; Placebo, 32). A: The proportion of patients who experienced a remission was 30.3% (CI, 19.6–42.8) in pH-2.4 g, 45.3% (CI, 32.9–58.2) in pH-3.6 g, 28.6% (CI, 17.9–41.3) in Time-2.25 g, and 9.4% (CI, 2.0–25.0) in Placebo. There were statistically significant differences from Placebo in all active-drug groups. B: Efficacy was archived in 45.5% (CI, 33.2–58.1) in pH-2.4 g, 64.1% (CI, 51.1–75.6) in pH-3.6 g, 49.2% (CI, 36.4–62.1) in Time-2.25 g, and 28.1% (CI, 13.8–46.7) in Placebo. There were significant differences from Placebo in both pH-3.6 g and Time-2.25 g.