Gastroenterology 2009;137:1880-1882,1934-1943.
In patients with moderately active ulcerative colitis, induction therapy with a 4.8 g/day mesalamine regimen is noninferior to induction with a 2.4 g/day regimen, and in fact, the higher dose may be more effective in difficult-to-treat patients, according to results of the randomized ASCEND III trial.
The international trial involved 772 patients with moderately active ulcerative colitis who were randomized to treatment with delayed release mesalamine given either with six 400-mg tablets each day, or six 800-mg tablets per day.
The primary endpoint was noninferiority of the higher versus the lower dose in terms of treatment success after 6 weeks. "Success" was defined as an improvement in Physician's Global Assessment score (with no worsening in any component), or complete remission.
In the December issue of Gastroenterology, Dr. William J. Sandborn of the Mayo Clinic, Rochester, Minnesota, and colleagues report that "the primary objective of noninferiority was met," given that improvement or remission was achieved in 66% of the 2.4 g/day group and 70% of the 4.8 g/day group (p = 0.17).
However, significantly more patients had clinical remission with the high dose than with the lower dose (43% vs 35%; p = 0.04).
"Treatment success at week 6 in favor of 4.8 g/day was generally consistent among most subgroups," the researchers report. "Of particular note" was the advantage of higher dose mesalamine for patients with refractory disease - particularly those who were previously treated with corticosteroids (p = 0.05), multiple ulcerative colitis drugs (p = 0.01), oral mesalamine (p = 0.07) or rectal therapies (p = 0.06).
Indeed, Dr. Sandborn commented by email, "Patients with moderate disease who have been previously treated with oral or rectal mesalamine or steroids appear to benefit most from the 4.8 g dose."
On the other hand, he added, "patients with mild disease and those with moderate disease who have not been previously treated can be successfully managed with mesalamine 2.4 g/day."
A similar proportion in both groups (about 9%) did not complete the study. The rate of adverse effects, which were mostly mild or moderate, was 20.6% in both treatment groups. Fifteen patients in each group (3.9%) withdrew from the study due to side effects. The most common cause of withdrawal was GI symptoms from ulcerative colitis.
In an accompanying editorial, Dr. Corey A. Siegel of Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, points out that the study led to "approval of the 800-mg mesalamine tablet with labeling to allow for 4.8 g dosing, but also an ultimate result showing that for many patients 2.4 g is as good as the full dose."
The study was funded by Procter & Gamble Pharmaceuticals, Inc., which markets mesalamine as Asacol. Six of the 11 authors have financial relationships with Proctor & Gamble.
In patients with moderately active ulcerative colitis, induction therapy with a 4.8 g/day mesalamine regimen is noninferior to induction with a 2.4 g/day regimen, and in fact, the higher dose may be more effective in difficult-to-treat patients, according to results of the randomized ASCEND III trial.
The international trial involved 772 patients with moderately active ulcerative colitis who were randomized to treatment with delayed release mesalamine given either with six 400-mg tablets each day, or six 800-mg tablets per day.
The primary endpoint was noninferiority of the higher versus the lower dose in terms of treatment success after 6 weeks. "Success" was defined as an improvement in Physician's Global Assessment score (with no worsening in any component), or complete remission.
In the December issue of Gastroenterology, Dr. William J. Sandborn of the Mayo Clinic, Rochester, Minnesota, and colleagues report that "the primary objective of noninferiority was met," given that improvement or remission was achieved in 66% of the 2.4 g/day group and 70% of the 4.8 g/day group (p = 0.17).
However, significantly more patients had clinical remission with the high dose than with the lower dose (43% vs 35%; p = 0.04).
"Treatment success at week 6 in favor of 4.8 g/day was generally consistent among most subgroups," the researchers report. "Of particular note" was the advantage of higher dose mesalamine for patients with refractory disease - particularly those who were previously treated with corticosteroids (p = 0.05), multiple ulcerative colitis drugs (p = 0.01), oral mesalamine (p = 0.07) or rectal therapies (p = 0.06).
Indeed, Dr. Sandborn commented by email, "Patients with moderate disease who have been previously treated with oral or rectal mesalamine or steroids appear to benefit most from the 4.8 g dose."
On the other hand, he added, "patients with mild disease and those with moderate disease who have not been previously treated can be successfully managed with mesalamine 2.4 g/day."
A similar proportion in both groups (about 9%) did not complete the study. The rate of adverse effects, which were mostly mild or moderate, was 20.6% in both treatment groups. Fifteen patients in each group (3.9%) withdrew from the study due to side effects. The most common cause of withdrawal was GI symptoms from ulcerative colitis.
In an accompanying editorial, Dr. Corey A. Siegel of Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, points out that the study led to "approval of the 800-mg mesalamine tablet with labeling to allow for 4.8 g dosing, but also an ultimate result showing that for many patients 2.4 g is as good as the full dose."
The study was funded by Procter & Gamble Pharmaceuticals, Inc., which markets mesalamine as Asacol. Six of the 11 authors have financial relationships with Proctor & Gamble.