Higher mesalamine dose more effective in moderately active ulcerative colitis

May 17, 2005

Two recent studies have found that for patients with moderately active ulcerative colitis, beginning treatment with twice the standard dose of mesalamine--4.8 grams per day rather than 2.4 grams--was more effective with no increase in side effects.

The consistent findings could change the way patients with moderately active ulcerative colitis are treated, said lead investigator Stephen Hanauer, MD, professor of medicine and clinical pharmacology and section chief of gastroenterology and nutrition at the University of Chicago Pritzker School of Medicine. Hanauer presented results from the trials, known as ASCEND I and II, at the Digestive Disease Week® 2005 annual scientific meeting in Chicago.

"Moderately active ulcerative colitis is a distinct disease classification that warrants aggressive treatment," Hanauer said. "Most patients suffer from moderately active disease, but very few receive 4.8 grams per day. Some are switched from standard dose mesalamine to other therapies before they are offered a higher dose."

"The definition and treatment of moderately active UC has traditionally been indistinct, typically grouped with either severe disease or, most often, with mild disease," added Asher Kornbluth, MD, associate clinical professor of medicine at Mount Sinai Medical Center and School of Medicine, New York, who also participated in the studies. "If approved, 4.8 grams per day will address an important need for this patient population."

The ASCEND (Assessing the Safety and Clinical Efficacy of a New Dose of 5-ASA) I and II studies--sponsored by Procter & Gamble, which makes both drugs--were randomized, controlled, phase-III clinical trials designed to compare 4.8 grams per day with an 800 mg tablet of mesalamine to 2.4 grams per day with a 400 mg tablet for six weeks. A total of 687 patients were randomized in ASCEND I and II, of which 423 analyzable patients (169 in ASCEND I, 254 in ASCEND II) had moderately active UC.

Measures of success were clinical, endoscopic, and physicians' global assessments. In these studies 72 percent of patients taking 4.8 grams a day of mesalamine achieved success compared to 58 percent of patients taking 2.4 grams of mesalamine, (p<0.05). Overall adverse events were similar in both treatment groups. The most common side effects (headache, gastrointestinal symptoms including abdominal pain, diarrhea, nausea, vomiting, flatulence, dyspepsia and respiratory symptoms consistent with respiratory infections or flu syndrome) were similar to those seen in previous lower-dose studies.

"Patients may take as many as twelve 400 milligram tablets a day to manage symptoms of the disease, including bleeding and cramping," Hanauer said. "The 800 milligram tablet allows patients with moderate ulcerative colitis to receive 4.8 grams per day of mesalamine by taking six tablets a day."

Mesalamine was approved in 1992 at a dose of 2.4 grams per day for the treatment of mild to moderate ulcerative colitis. The most frequent adverse events reported for treatment at that level versus placebo, were headache (35% vs. 36%), abdominal pain (18% vs. 14%), and eructation (16% vs. 15%).

Patients who are hypersensitive to salicylates, such as aspirin, should not take mesalamine. Caution should be exercised when using mesalamine in patients with kidney disease. All patients should have an evaluation of renal function prior to beginning treatment and periodically while on therapy. As with other mesalamine-containing products, serious adverse events may occur.

About Ulcerative Colitis

Ulcerative colitis involves inflammation of the lining of the colon and rectum. It varies in clinical severity with patients having mild, moderate or severe disease. Treatment depends on the severity of disease.

It causes flares followed by periods of remission. During a flare, in which the rectum or colon become inflamed, people experience symptoms such as diarrhea, rectal bleeding, abdominal cramping and an urgent need to go to the bathroom. Flares can vary in duration and intensity.

While ulcerative colitis is a lifelong condition, flares can be controlled with medication.

Ulcerative colitis affects people of all ages, but often is diagnosed during early adulthood. The causes of this condition are unknown, but may involve heredity, infection or the immune system.

About Digestive Disease Week

Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy, and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 14-19, 2005 in Chicago. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology.

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