Tu1122 Optimal Dosing of Mesalamine for Maintenance of Clinical Remission in Patients With Distal Ulcerative Colitis and Residual Endoscopic Activity: A Subgroup Analysis of a Double-Blind, Double-Dummy, Randomized, Controlled, Dose-Ranging Study

Abstract

Introduction: Proctosigmoiditis is the most frequent phenotype of ulcerative colitis (UC). Recently, it has been shown that 3 g oral mesalamine (Salofalk® granules) once daily (OD) showed higher rates for maintaining remission compared to lower doses of mesalamine, especially in patients with residual signs of endoscopic inflammatory activity at the start of the treatment.1 But, whether patients with proctosigmoiditis and residual endoscopic inflammation might profit from a higher dose is unclear. Aims: To study optimal dosing of mesalamine for maintenance of remission in proctosigmoiditis with residual endoscopic activity at the start of treatment. Methods: This was a stratified subgroup analysis of a double-blind, double-dummy, randomized, multicenter, comparative phase III study, in which the clinical outcome (i.e., clinical remission at wk 52) was analyzed in patients with proctosigmoiditis according to the presence of residual endoscopic inflammation at the start of maintenance treatment. Patients with active UCwho had recently achieved clinical (Clinical Activity Index [CAI] ,= 4) and an endoscopic index (EI) ,= 3 were randomized to mesalamine (Salofalk® granules) 3g OD, 1.5g OD, or 0.5g TID for 12 months. Remission at study end was defined as a CAI of ,= 4 with no increase of .=3 points from baseline. Results: A total of 647 patients who came into remission within the last 12 weeks prior to baseline were randomized and treated; 217 patients with 3g OD, 212 with 1.5g OD, and 218 with 0.5g TID mesalamine. All three treatment regimens were efficacious in maintaining clinical remission of UC over 1 year. A subgroup analysis in patients with vs. without residual mucosal damage showed that 3g OD performed best in the subgroup with residual inflammation at start of treatment. A further subgroup analysis of patients with residual mucosal damage according to extent of UC revealed that 3g OD performed best independently from the extent (see table below). Conclusions: A dosage of 3g mesalamine (Salofalk® granules) once daily showed the best efficacy for prevention of relapse in UC compared to a daily dose of 1.5g mesalamine, especially in patients with residual signs of inflammation, even in the distal colon. Reference: (1) Kruis W, Jonaitis L, Pokrotnieks J, Mikhailova TL, Horynski M, Batovsky M, et al. Aliment Pharmacol Ther. 2011;33(3):313-22. Support: Dr. Falk Pharma GmbH, Freiburg, Germany Clinical remission by mucosal damage and extent of mucosal damage (ITT):