Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis

Abstract

Aim: Maintenance treatment in ulcerative colitis should be as convenient as possible, to increase the chance of compliance. MMX mesalazine is a once-daily, high-strength (1.2 g/tablet) formulation of 5-aminosalicylic acid. This study evaluated the safety and efficacy of MMX mesalazine dosed once or twice daily as maintenance therapy in patients with ulcerative colitis.

Methods: This multicentre, randomised, open-label trial enrolled patients with strictly defined clinical and endoscopic remission, immediately following an episode of mild to moderate ulcerative colitis. Patients were randomised to MMX mesalazine 2.4 g/day as a single (2x1.2 g tablet) or divided dose (1x1.2 g tablet twice daily) for 12 months.

Results: 174 patients (37.9%; safety population n = 459) experienced 384 adverse events, the majority of which were mild or moderate in intensity. Eighteen patients (3.9%), nine in each group, experienced a total of 22 serious adverse events (10 in the once-daily and 12 in the twice-daily group). Most serious adverse events were gastrointestinal, experienced by 5 patients in the once-daily and 4 in the twice-daily group. At month 12, 64.4% (efficacy population, n = 451) of patients in the once-daily and 68.5% of patients in the twice-daily group were in clinical and endoscopic remission (p = 0.351). At month 12, 88.9% and 93.2% in each group, respectively, had maintained clinical remission (were relapse free).

Conclusions: MMX mesalazine 2.4 g/day administered as a single or divided dose demonstrated a good safety profile, was well tolerated and was effective as maintenance treatment. High clinical and endoscopic remission rates can be achieved with once-daily dosing.

Trial registration number: NCT00151944.

Figure 1. (A) Overall study design (safety population) and (B) patient flow in the 12-month, randomised, maintenance phase of study SPD-476-303. *Patients excluded from the efficacy population because of study centre Good Clinical Practice non-compliance. ^†The “per-protocol” population included only those patients in the efficacy population who met the strict protocol-defined criteria for remission. AEs, adverse events; SAEs, serious adverse events.

Figure 2. Remission rates at month 0 and month 12 in the efficacy and “per-protocol” populations following treatment with MMX mesalazine 2.4 g/day given once daily or twice daily.

Figure 3. Remission rates at month 0 and month 12 by study entry route (8-week extension phase of study 303 or parent studies) in the efficacy population following treatment with MMX mesalazine 2.4 g/day given once daily or twice daily.