Original article
Effect of Once- or Twice-Daily MMX Mesalamine (SPD476) for the Induction of Remission of Mild to Moderately Active Ulcerative Colitis

https://doi.org/10.1016/j.cgh.2006.10.025Get rights and content

Background & Aims: SPD476 (MMX mesalamine), a novel, once-daily mesalamine formulation, uses MMX Multi Matrix System (MMX) technology to delay and extend delivery of active drug throughout the colon. We performed a randomized, double-blind, parallel-group, placebo-controlled, multicenter phase III study in patients with mild to moderately active ulcerative colitis. Methods: Two hundred eighty patients with mild to moderately active ulcerative colitis received MMX mesalamine 2.4 g/day given twice daily (n = 93), 4.8 g/day given once daily (n = 94), or placebo (n = 93) for 8 weeks. The primary end point was the percentage of patients in clinical and endoscopic remission (modified ulcerative colitis disease activity index score of ≤1, with a score of 0 for rectal bleeding and stool frequency, and at least a 1-point reduction in sigmoidoscopy score) at week 8. Patients with mucosal friability were not considered to have achieved this end point. Results: Clinical and endoscopic remission at week 8 was achieved by 34.1% and 29.2% of patients receiving MMX mesalamine 2.4 g/day given twice daily and MMX mesalamine 4.8 g/day given once daily, respectively, versus 12.9% receiving placebo (P < .01). MMX mesalamine was generally well-tolerated. Conclusions: MMX mesalamine given once or twice daily is well-tolerated and, compared with placebo, demonstrated efficacy for the induction of clinical and endoscopic remission in mild to moderately active ulcerative colitis.

Section snippets

Participants

Eligible male and female patients aged ≥18 years with newly diagnosed or relapsing (relapsed ≤6 weeks before baseline) mild to moderately active UC (score of 4–10 on a modified version of the Sutherland UC–disease activity index16 (UC-DAI) (Table 1), with a sigmoidoscopy score ≥1 and a Physician’s Global Assessment (PGA) score ≤2 with compatible histology, were enrolled in the study.

Patients were excluded from the study if they had: severe UC defined by PGA >2; current relapse lasting >6 weeks;

Results

The study was conducted between September 2003 and January 2005. Two hundred eighty patients were randomized from 52 centers in Australia (n = 3), the Czech Republic (n = 16), India (n = 71), Mexico (n = 18 [this country group also included 1 center in Costa Rica]), New Zealand (n = 12), Romania (n = 11), the Ukraine (n = 78), and the USA (n = 71). Ten patients underwent forced randomization (5 in each of the SPD476 2.4 g/day given twice daily and SPD476 4.8 g/day given once daily groups).

Discussion

This study demonstrates that MMX mesalamine, given once or twice daily, was efficacious for the induction of clinical and endoscopic remission of mild to moderately active UC. Significantly more patients receiving either dose of MMX mesalamine achieved clinical and endoscopic remission than those receiving placebo (P < .01). Approximately 1 in 3 patients in both MMX mesalamine groups achieved clinical and endoscopic remission compared with 1 in 8 in the placebo group (a 2.3-fold to 2.6-fold

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    Supported by Shire Pharmaceuticals Inc. Gary Lichtenstein, Michael Kamm, and William Sandborn have served as consultants for Shire and have participated in continuing medical education events indirectly sponsored by Shire Pharmaceuticals Inc. Andrew Lyne, Kristen H. Lees, and Raymond Joseph are employees of Shire Pharmaceuticals. Gary Lichtenstein has received honoraria and research support from Shire Pharmaceuticals, Proctor and Gamble, Salix Pharmaceuticals, and Axcan Pharmaceuticals.

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