Randomised non-inferiority trial: 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis.

BACKGROUND: High concentration mesalazine formulations are more convenient than conventional low concentration formulations for the treatment of ulcerative colitis (UC). AIM: To compare the efficacy and safety of 1600 mg and 400 mg tablet mesalazine formulations. METHODS: Patients with mild-to-moderate active UC (Mayo Clinic Score >5; N=817) were randomised to 3.2 g of oral mesalazine, administered as two 1600 mg tablets once, or four 400 mg tablets twice daily. We hypothesised that treatment with the 1600 mg tablet was non-inferior (within a 10% margin) to the 400 mg tablet for induction of clinical and endoscopic remission at week 8. Open-label treatment with the 1600 mg tablet continued for 26-30 weeks based on induction response. Predictors of treatment response were also explored. RESULTS: At week 8, remission occurred in 22.4% and 24.6% of patients receiving the 1600 mg and 400 mg tablets, respectively (absolute difference -2.2%, 95% CI: -8.1% to 3.8%, non-inferiority P=.005). Endoscopic and histopathologic disease activity, leucocyte concentration and age were significantly associated with clinical remission (P=.022, .042, .014 and .023, respectively). At week 38, 43.9% (296/675) of patients who continued treatment with the 1600 mg formulation were in remission, including 70.3% (142/202) of patients who received a reduced dose of mesalazine (1.6 g/d). The overall incidence of serious adverse events was low. CONCLUSIONS: Induction therapy with 3.2 mg mesalazine using two 1600 mg tablets once-daily was statistically and clinically non-inferior to a twice-daily regimen using four 400 mg tablets (NCT01903252).

Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis.

BACKGROUND: Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited. AIM: To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis. METHODS: A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline. RESULTS: The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group. CONCLUSION: Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.

Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial.

OBJECTIVES: 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. DESIGN: A randomised, double-blind, double-dummy, parallel group, multicentre, international, phase III non-inferiority study. SETTING: 54 centres in 13 countries. PATIENTS: 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. INTERVENTIONS: 8-week treatment with either 3 g OD or 1 g TID mesalazine granules. MAIN OUTCOME MEASURES: 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.