Once-daily formulation of mesalamine induces, maintains remission in patients with ulcerative colitis

A once-daily formulation of mesalamine that relies on multimatrix (MMX) technology is effective at inducing and maintaining remission in patients with ulcerative colitis (UC), with no significant gender difference in the response rate, according to studies presented at Digestive Disease Week (DDW) 2006 in Los Angeles, Calif, and at the American College of Gastroenterology (ACG) Annual Scientific Meeting in Las Vegas, Nev.

With current formulations of 5-ASA, 8 to 16 pills per day in 3 to 4 divided doses are necessary for induction of response or remission. Patients on maintenance therapy must take ≥1 pill 3 times daily indefinitely.

"We know that 60% of patients on mesalamine in remission don't take medication after 6 months of treatment," said Gary Lichtenstein, MD, Division of Gastroenterology, University of Pennsylvania, Philadelphia, Pa. Patients who are not adherent to their maintenance 5-ASA regimen have a >5-fold increased risk of recurrence compared with individuals who take ≥80% of their prescribed dose, he said.

Data have demonstrated that the MMX formulation of mesalamine is as effective as currently available formulations, with the added benefit of once-daily dosing.

At DDW, researchers presented 2 phase 3 studies (studies 301 and 302) demonstrating that MMX mesalamine induced remission of active mild-to-moderate UC in patients who either were switched from other oral 5-ASA therapies or were 5-ASA-naïve. Both once-daily and twice-daily MMX mesalamine induced remission in patients with left-sided or extensive UC.

Studies 301 and 302 were prospective, randomized, multicenter, double-blind, placebo-controlled, 8-week studies examining the efficacy and tolerability of MMX mesalamine in once-daily and twice-daily dosing.

The data were combined for patients receiving MMX mesalamine 2.4 g/d (once or twice daily; n=172), MMX mesalamine 4.8 g/d (once daily; n=174), or placebo (n=171).

Approximately 37.2% of patients assigned to MMX mesalamine 2.4 g/d achieved remission versus 17.5% of patients assigned to placebo (P<.001). Significantly more patients randomized to MMX mesalamine 4.8 g/d also achieved remission versus patients randomized to placebo (35.1% vs 17.5%; P<.001).

In patients with left-sided UC, MMX mesalamine at either 2.4 or 4.8 g/d was associated with significantly greater remission versus placebo (P<.001 for 2.4 g/d vs placebo; P=.006 for 4.8 g/d vs placebo).

Further analyses of MMX mesalamine in studies 301 and 302 were presented at the ACG meeting. Induction of remission was measured in study 302 and was used to calculate the number needed to treat to induce 1 remission after 8 weeks of therapy. In this study, 341 patients with active mild-to-moderate UC were randomized to receive MMX mesalamine 2.4 g/d once daily, MMX mesalamine 4.8 g/d once daily, mesalamine 2.4 g/d 3 times daily, or placebo.

Remission in these studies was defined as a modified UC disease activity index (UC-DAI) of ≤1, with a rectal bleeding and stool frequency score of 0, no mucosal friability, and ≥1-point reduction in sigmoidoscopy score from baseline. (The standard UC-DAI allows patients with mild friability to be given a sigmoidoscopy score of 1. In the modified UC-DAI, however, patients with any mucosal friability were given a score ≥2 and were not, therefore, considered to be in remission). "These were very stringent criteria to meet the definition of remission," Dr Lichtenstein stated.

Remission rates were significantly greater with the once-daily MMX mesalamine dosages versus placebo (P≤.01). In contrast, mesalamine 2.4 g/d 3 times daily was not significantly superior to placebo in inducing remission.

The number needed to treat to induce remission with either once-daily MMX mesalamine dosage was 6. The number needed to treat to induce remission with mesalamine 3 times daily was 10.

In a pooled analysis of studies 301 and 302, remission rates were analyzed separately for men and women. A significantly greater proportion of both men and women receiving MMX mesalamine 2.4 or 4.8 g/d achieved remission at Week 8 compared with placebo. Relative to placebo, MMX mesalamine increased the odds of achieving remission by approximately 2.6-fold for men and 3.0-fold for women, suggesting that there was no difference in the magnitude of MMX mesalamine efficacy between sexes, said Dr Lichtenstein.

Although gender specificity did affect remission rates, logistic regression analysis of treatment by gender interaction demonstrated that the efficacy of MMX mesalamine was not dependent on sex.