Objectives: To determine the therapeutic equivalence and safety of once daily (OD) versus three times daily (TID) dosing of a total daily dose of 3g Salofalk® (mesalazine) granules in patients with active ulcerative colitis (UC).
Design: A randomised, double-blind, double-dummy, parallel group, multicentre, international, Phase III non-inferiority study.
Setting: 54 centers in 13 countries.
Patients: 380 patients with confirmed diagnosis of established or first attack of UC (Clinical Activity Index [CAI] > 4 and Endoscopical Index ≥ 4 at baseline) were randomized and treated.
Interventions: 8-week treatment with either 3g OD or 1g TID mesalazine granules.
Main Outcome Measures: Clinical remission (CAI £ 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 PP population, 83% in the OD group (N=171) and 78% in the TID group (N=174) achieved clinical remission (p<0.0001 for non-inferiority). Significantly more patients (ITT) 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 (ITT) achieved endoscopical remission, and 41% in the OD group and 47% in the TID group achieved histological remission (ITT). About 80% of all patients preferred a OD dosing. The two dosing regimens were equally safe and well-tolerated.
Conclusions: OD 3g mesalazine granules are as effective and safe as a TID 1g schedule. With respect to the best possible adherence of the patients to the treatment, OD dosing of mesalazine should be the preferred application mode in active UC.