P184. Once-daily versus twice-daily mesalazine for mild to moderately active ulcerative colitis: Mucosal healing and early response data from MOTUS, a multicentre, controlled, randomised, investigator-blinded study
M. Pierik1, H. Hagège2, G. Tucat3, A. Masclee4, O. Dewit5, C. Probert6, P. Broberg7, D. Aoucheta8
1Maastricht University Medical Center, Netherlands; 2Lyon Sud Hospital, France; 3ANGH, France; 4Club de Réflexion des Cabinets et Groupes d'Hépato-Gastroentérologie, France; 5UCL Saint Luc, Belgium; 6Institute of Translational Medicine, United Kingdom; 7Ferring Pharmaceuticals, Switzerland; 8Ferring SAS, France
Background: Reduced dosing frequency makes treatment easier and improves compliance with 5‑ASA in ulcerative colitis (UC). The multicentre, controlled, randomised, investigator-blinded MOTUS study (sponsor: Ferring Pharmaceuticals; NCT00737789) studied non-inferiority of OD vs BD 5‑ASA (Pentasa®) for the induction of remission in active UC, with additional focus on mucosal healing and early response.
Methods: Patients (pts) with mild to moderately active UC (proctitis only excluded) were randomised to 5‑ASA (prolonged release granules, new formulation) 4 g/day for 8 weeks: 2x 2 g OD or 1x 2 g BD. All pts received 5‑ASA enema (1 g/day) for the first 4 weeks. Endpoints included: induction of remission (primary endpoint); mucosal healing (UC-DAI endoscopic mucosal appearance score </=1); time to cessation of bleeding (first bleeding-free day); and time to remission (normal stool frequency and cessation of bleeding; pts' diaries). Normal stool frequency (UC-DAI stool frequency subscore 0), clinical remission (abbreviated UC-DAI score 0), treatment failure (need for disallowed treatments), and non-bleeding stools (UC-DAI rectal bleeding subscore 0) at week 4 were also analysed. Observed case analyses are shown. Categorical variables were analysed by Cochran-Mantel Haenszel chi-squared test and time-to-endpoint variables by Cox survival analysis, all adjusted by country.
Results: 206 pts were enrolled and 202 included in intent-to-treat analyses (n = 101 per arm). OD 5‑ASA was superior to BD for mucosal healing at week 8 (87.5% vs 71.1% respectively; difference 16.4% [CIs 4.528.2]; P = 0.007). Median time to remission was significantly shorter with OD vs BD dosing (26 vs 28 days, respectively; P = 0.042). Time to cessation of bleeding was not significantly different (13 vs 21 days, respectively; P = 0.139). At week 4, significantly more pts had normal stool frequency with OD vs BD dosing (P = 0.013); there was no significant difference in rates of clinical remission, treatment failure or non-bleeding stools.
Conclusions: 4 g OD 5‑ASA was non-inferior to BD dosing. Moreover, significantly more pts with active UC achieved mucosal healing at week 8 and normal stool frequency at week 4 with 4 g 5‑ASA OD vs BD, and median time to remission was significantly shorter with OD therapy. Other secondary endpoints were similar with OD and BD dosing at week 4. These data are consistent with those seen for maintenance of remission, and suggest that OD Pentasa® offers potential benefits to pts.