Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: a double-blind, randomized study.
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).
Ito
Hiroaki
H
Digestive Disease Center of Excellence, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, Osaka, Japan.
Iida
Mitsuo
M
Matsumoto
Takayuki
T
Suzuki
Yasuo
Y
Sasaki
Hidetaka
H
Yoshida
Toyomitsu
T
Takano
Yuichi
Y
Hibi
Toshifumi
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D019804:Mesalamine / Q000737:chemistry / Q000627:therapeutic use*; D008875:Middle Aged; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012074:Remission Induction; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004364:Pharmaceutical Preparations; D019804:Mesalamine