P183. Once-daily versus twice-daily mesalazine for active ulcerative colitis: Efficacy results from MOTUS, a multicentre, controlled, randomised, investigator-blinded study
B. Flourié1, H. Hagège2, G. Tucat3, A. Masclee4, O. Dewit5, C. Probert6, P. Broberg7, D. Aoucheta8
1Lyon Sud Hospital, France; 2ANGH, France; 3Club de Réflexion des Cabinets et Groupes d'Hépato-Gastroentérologie, France; 4Maastricht University Medical Center, Netherlands; 5UCL Saint Luc, Belgium; 6Institute of Translational Medicine, United Kingdom; 7Ferring Pharmaceuticals, Switzerland; 8Ferring SAS, France
Background: In ulcerative colitis (UC) less frequent dosing of 5‑ASA makes treatment easier and improves compliance. PODIUM demonstrated non-inferiority, and superiority (p = 0.02), of 2 g once-daily (OD) vs 1 g twice-daily (BD) Pentasa® sachet (prolonged release granules) for the maintenance of remission in UC (Dignass, CGH 2009). The objective of MOTUS (sponsor: Ferring Pharmaceuticals; NCT00737789) was to show non-inferiority of 4 g OD Pentasa® granules (new concentrated formulation) vs standard 2 g BD dosing for the induction of remission in active UC.
Methods: Pts with active mild-to-moderate UC were randomised to 5‑ASA granules 4 g/d: 2x 2 g OD or 1x 2 g BD. All pts also received 5‑ASA enema (1 g/d) for 4 wks. Primary endpoint: clinical and endoscopic remission at wk 8 (UC-DAI score </=1). Secondary endpoints: clinical remission at wks 4, 8, 12 (normal stool frequency, no bloody stools, no active disease by physician's global assessment); mucosal healing at wk 8 (UC-DAI endoscopic mucosal appearance score </=1). Statistical data are from intent-to-treat (ITT) and per-protocol (PP) analyses.
Results: 206 pts were enrolled (OD n = 102; BD n = 104). Primary endpoint was met (Table): 5‑ASA 4 g OD was non-inferior to 2 g BD, the lower limit of the two-sided 95% CI of the difference in remission rate was −3%, within the pre-specified non-inferiority margin of −15%. Secondary endpoints for OD vs BD: clinical remission at wks 4, 8, 12: 39.8% vs 27.6% (p = 0.07), 45.1% vs 40.8% (p = 0.53), 92.4% vs 79.4% (p = 0.13); mucosal healing at wk 8 by UC-DAI sub-score </=1: 87.5% vs 71.1% (p = 0.007).
|Primary endpoint||5‑ASA OD N (%)||5‑ASA BD N (%)||Difference, % [95% CI]||Non-inferiority*|
|ITT||52/101 (52.1)||42/101 (41.8)||10.4 [−3.4; 24.1]||NI|
|PP||48/79 (61.0)||37/77 (48.3)||12.8 [−2.7; 28.2]||NI|
Conclusions: MOTUS showed non-inferiority of Pentasa® 4 g OD vs 2 g BD in pts with active UC. The primary endpoint was met in all analysis groups. All secondary endpoints were also non-inferior for OD vs BD, with mucosal healing being significantly better with OD. The data are consistent with PODIUM (maintenance 5‑ASA). These studies show that OD treatment with 5‑ASA granules is at least as effective as BD dosing, allowing treatment to be personalised to pt preference.