Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.
OBJECTIVE
To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3 g Salofalk (mesalazine) granules in patients with active ulcerative colitis.


METHODS
A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study.


METHODS
54 centres in 13 countries.


METHODS
380 patients with confirmed diagnosis of established or first attack of ulcerative colitis (clinical activity index (CAI)>4 and endoscopic index > or =4 at baseline) were randomised and treated.


METHODS
8-week treatment with either 3 g OD or 1 g TID mesalazine granules.


METHODS
Clinical remission (CAI< or =4) at study end.


RESULTS
380 patients were evaluable for efficacy and safety by intention-to-treat (ITT); 345 for per protocol (PP) analysis. In the ITT population, 79.1% in the OD group (n = 191) and 75.7% in the TID group (n = 189) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients with proctosigmoiditis achieved clinical remission in the OD group (86%; n = 97) versus the TID group (73%; n = 100; p = 0.0298). About 70% of patients in both treatment groups achieved endoscopic remission, and 35% in the OD group and 41% in the TID group achieved histological remission. About 80% of all patients preferred OD dosing. Similar numbers of adverse events occurred in 55 patients (28.8%) in the OD group and in 61 patients (32.3%) in the TID group, indicating that the two dosing regimens were equally safe and well tolerated.


CONCLUSIONS
OD 3 g mesalazine granules are as effective and safe as a TID 1 g schedule. With respect to the best possible adherence of patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active ulcerative colitis.
Kruis
W
W
Evangelisches Krankenhaus Kalk, University of Cologne, Cologne, Germany. sallhoff@evkk.de
Kiudelis
G
G
Rácz
I
I
Gorelov
I A
IA
Pokrotnieks
J
J
Horynski
M
M
Batovsky
M
M
Kykal
J
J
Boehm
S
S
Greinwald
R
R
Mueller
R
R
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D016009:Chi-Square Distribution; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D003113:Colonoscopy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D010349:Patient Compliance; D018401:Sample Size; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine