Prolonged MMX® mesalazine therapy in patients with acute, mild-to-moderate ulcerative colitis who fail initial mesalazine treatment may prevent a requirement for therapeutic escalation

Introduction: MMX® mesalazine (Mezavant®, Shire Pharmaceuticals Inc., USA; MMX; Cosmo Technologies Ltd, Ireland) has been observed to successfully induce remission in patients with mild-to-moderate ulcerative colitis (UC) in two, phase III, placebo-controlled (parent) studies by Lichtenstein et al. (SPD476–301) and Kamm et al. (SPD476–302). Objectives: We examine the proportion of patients who did not achieve remission following up to 8 weeks' initial treatment, but who may respond to a further 8 weeks' MMX mesalazine. Methods: In the parent studies, patients were randomised to receive MMX mesalazine 2.4g/day (once daily [QD] or 1.2g twice daily [BID]), 4.8g/day (QD), Asacol® (mesalazine) delayed-release tablets (Warner Chilcott, USA) 2.4g/day (0.8g three times daily [TID]) or placebo for up to 8 weeks. Patients who did not achieve clinical and endoscopic remission in these studies were eligible to receive additional high-dose (4.8g/day [2.4g BID]) MMX mesalazine therapy as part of an 8-week, open-label, extension study by Kamm et al. (SPD476–303). Clinical and endoscopic remission was stringently defined as modified UC Disease Activity Index score of ≤1, calculated as: stool frequency and rectal bleeding scores of 0; a combined Physician's Global Assessment and sigmoidoscopy score of ≤1; no mucosal friability; and ≥1-point reduction in sigmoidoscopy score from baseline. Results: 304 patients were included in the efficacy population of the 8-week extension phase. Overall, 59.5% of patients achieved stringently defined clinical and endoscopic remission. When considering remission by previous treatment in the parent study, no notable differences were observed overall: placebo=57.0%; MMX mesalazine 2.4g/day (QD or BID)=61.5%; MMX mesalazine 4.8g/day (QD)=60.3%; Asacol 2.4g/day (0.8g TID; included as a reference arm in the Kamm et al. [SPD476–302] parent study only)=61.0%. Conclusions: The majority of patients who failed to achieve stringently defined remission through an initial course of mesalazine therapy were able to achieve remission after up to an additional 8 weeks' MMX mesalazine. Therefore, in such patients, additional therapy with MMX mesalazine beyond an initial 8 weeks, may avoid unnecessary therapeutic escalation to agents such as steroids. This abstract has been published previously to meetings outside of Germany. Europe: European Crohn's and Colitis Organisation, JCC Supplements 2008;2(1): S21 (P053). Canada: Canadian Digestive diseases Week (CDDW), Can J Gastroenterol 2008;22(Suppl. SA):Abstract 081. USA: American Society of Gastroenterology (ACG), Am J Gastroenterol 2007;102(s2): Abstract 953