Once-Daily, High-Concentration MMX Mesalamine in Active Ulcerative Colitis

Background & Aims: SPD476 (LIALDA™ in the US; MEZAVANT™ in the EU; otherwise known as MMX mesalamine; Shire Pharmaceuticals Inc., Wayne, PA, under license from Giuliani SpA, Milan, Italy) is a novel, once-daily, high-strength (1.2 g/tablet) formulation of mesalamine, utilizing MMX Multi Matrix System (MMX) technology designed to deliver the active drug throughout the colon. We performed a double-blind, multicenter study, comparing MMX mesalamine vs placebo for the treatment of active ulcerative colitis. A delayed-release oral mesalamine (ASACOL; Procter & Gamble, Cincinnati, OH) reference arm was included.Methods: Three hundred forty-three patients with active, mild-to-moderate ulcerative colitis received MMX mesalamine 2.4 g/day or 4.8 g/day given once daily, ASACOL 2.4 g/day given in 3 divided doses, or placebo for 8 weeks. The primary end point was the proportion of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index of ≤1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a ≥1-point reduction in sigmoidoscopy score from baseline). Results: A significantly greater proportion of patients receiving MMX mesalamine 2.4 g/day given once daily (40.5%; P = .01) and 4.8 g/day given once daily (41.2%; P = .007) achieved clinical and endoscopic remission at week 8, vs placebo (22.1%). The clinical and endoscopic remission rate for ASACOL (32.6%; P = .124) was not significantly superior to placebo. All active treatments were well-tolerated. Conclusions: Once-daily MMX mesalamine was efficacious and well-tolerated for the induction of clinical and endoscopic remission. MMX mesalamine offers effective and convenient mesalamine therapy, potentially improving treatment compliance.

Abbreviations used in this paper: 5-ASA, 5-aminosalicylate, AE, adverse event, CI, confidence interval, ITT, intent-to-treat, LOCF, last observation carried forward, MMX, MMX Multi Matrix System, PP, per protocol, PGA, Physician’s Global Assessment, QD, once daily, SAE, serious adverse event, TID, 3 times daily, UC-DAI, ulcerative colitis-disease activity index