Source: DGNews  |  Posted 3 years ago

By Deborah Brauser

ORLANDO, Fla -- October 10, 2008 -- A daily 4.8-g dose of mesalamine delayed-released (DR) appears to be effective for treatment of moderately active ulcerative colitis (UC) in patients with a history of difficult-to-treat disease, according to data from 3 phase 3 trials presented here at the American College of Gastroenterology (ACG) 73rd Annual Scientific Meeting.

Lead investigator Stephen Hanouer, MD, University of Chicago Medical Center, Chicago, Illinois, discussed the results here in a poster session on October 6.

This combination analysis was designed to determine the efficacy of mesalamine DR for the treatment of moderately active UC using an investigational 800-mg tablet, while identifying patients more likely to respond to the higher 4.8-g daily dose.

Dr. Hanouer and colleagues pooled data from the Assessing the Safety and Clinical Efficacy of a New Dose of 5-ASA (ASCEND) I, II, and III trials, which were all multicentre, randomised, double-blind, 6-week, active-controlled studies.

A total of 1,220 patients with moderately active UC, as defined by a Physician's Global Assessment (PGA) score of 2, received mesalamine DR at a daily dose of 4.8 g or 2.4 g.

The primary endpoint of the analysis was treatment success defined as improvement in PGA score from baseline based on clinical assessments of rectal bleeding (RB), stool frequency (SF), and sigmoidoscopy, with no worsening in any individual clinical assessment. The symptoms of UC, RB, and SF were all evaluated identically in all 3 studies. Improvement in RB and SF was defined as a decrease from baseline of at least 1 point based on a 4-point scale and clinical remission was defined as resolution of both RB and SF.

At the end of 6 weeks, treatment success occurred in 69% of patients receiving the 4.8-g dose and in 62% of the patients on 2.4-g dose (P = .006). More patients receiving 4.8 g versus 2.4 g had RB improvement (83% vs 79%, P = .04), SF improvement (78% vs 73%, P = .07), and clinical remission (43% vs 37%, P = .06) at the end of the 6 weeks.

In addition, a therapeutic advantage of the 4.8-g dose versus the 2.4-g dose was seen in patients who previously used UC medications.

Said Dr. Hanouer, "It's been difficult to demonstrate a dose response for mesalamine between 2.4 and 4.8 g. We've identified in the previous ASCEND trials that the patients with more moderate disease seem to respond better to the higher dose and patients with mild disease to the lower dose. Then the question becomes -- how do you define moderate disease both on clinical terms as well as with their experience?"

He continued, "We're seeing that the patients who have not responded before, who required steroids in the past, who required rectal therapy, who have failed low-dose mesalamine, are the ones who respond to the higher doses. The majority of the patients, however, who present with mild to moderate disease, do well at the 2.4-g dose."

He said, "I would say the number 1 take-away is: Consider the patient's history and disease. [The dosage rate] is not written in stone. You can modify it."

[Presentation title: Increased Efficacy of Delayed-Release Mesalamine 4.8 g/d (800 mg tablet) Compared to 2.4 g/d (400 mg tablet) for Treatment of Moderately Active Ulcerative Colitis in Patients With a History of More Difficult to Treat Disease: Combined Analysis From Three Randomized, Double-Blind, Active-Controlled Trials. Abstract P-284]