Gastroenterology

Gastroenterology

Volume 132, Issue 1, January 2007, Pages 66-75
Gastroenterology

Clinical–alimentary tract
Once-Daily, High-Concentration MMX Mesalamine in Active Ulcerative Colitis

https://doi.org/10.1053/j.gastro.2006.10.011Get rights and content

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.

Section snippets

Participants

Male and female patients aged ≥18 years who had newly diagnosed or relapsing (relapsed ≤6 weeks prior to baseline) active, mild-to-moderate UC (score of 4–10 on a modified UC-disease activity index [UC-DAI], with a sigmoidoscopy score ≥1 and a Physician’s Global Assessment [PGA] score ≤2) with compatible histology were eligible for enrollment in this study. The modified UC-DAI scoring system used in this study was based on that developed by Sutherland et al,19 in which patients found to have

Participant Flow

The study was conducted between December 4, 2003 and October 20, 2004 and 343 patients were randomized to treatment (Figure 1). Thirty-five patients underwent forced randomization; this affected treatment groups similarly (MMX mesalamine 2.4 g/day given QD, n = 10; MMX mesalamine 4.8 g/day given QD, n = 8; ASACOL, n = 8; placebo, n = 9). Two patients were randomized in error and excluded from the study. Both of these patients were found to have a positive stool culture. Neither patient received

Discussion

Our study was designed to evaluate the efficacy and tolerability of MMX mesalamine, a novel formulation of 5-ASA designed to deliver the active drug throughout the colon in a single daily dose, potentially improving patient compliance and thus overall treatment success.

The data from our study show that MMX mesalamine 2.4 g/day or 4.8 g/day given once per day was well tolerated and efficacious for the induction of clinical and endoscopic remission of active, mild-to-moderate UC. Both doses of

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  • Cited by (328)

    • Mesalamine in the Initial Therapy of Ulcerative Colitis

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      These coatings release at a pH of greater than 7, beginning in the terminal ileum and colon.14,15 The hydrophilic component allows the tablet to swell to a viscous gel state, allowing for proposed slower diffusion throughout the small bowel and colon, while the lipophilic core repels water from entering the core of the tablet prolonging its half-life.14,15 This nature also allows for once-daily administration.14

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    Supported by Shire Pharmaceuticals Inc.

    1

    M.K. and W.J.S. have served as consultants for and have participated in continuing medical education events indirectly sponsored by Shire Pharmaceuticals Inc.

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