DDW: Once-Daily Mesalamine Effective In Ulcerative Colitis

WASHINGTON, May 24 -- For patients with active ulcerative colitis, an investigational once-daily formulation of mesalamine is effective and safe, a German researcher said here.

The 3-mg Salofalk granules worked as well as the same drug taken in 1-mg doses three times a day, according to Wolfgang Kruis, M.D., of the University of Cologne.

"Once-daily dosage should be the preferred application," Dr. Kruis told researchers at Digestive Disease Week.

The reason for investigating the issue, he said, is that less frequent dosing has been shown to increase adherence to therapy and to improve clinical outcomes.

In a phase III trial, he and colleagues randomized 380 patients to get:

• A 3 mg dose of mesalamine every morning, with a 1 g placebo at noon and in the evening.
• Or a 1 mg dose of mesalamine three times daily with a 2 g placebo in the morning.

The primary endpoint of the eight-week study was clinical remission, defined as a reduction of four or more points on the clinical activity index. The researchers also evaluated a range of secondary endpoints, including mucosal healing, Dr. Kruis said.

Both on a per-protocol and intent-to-treat basis, the proportion of patients achieving clinical remission was not different statistically. Specifically:

• In the per-protocol analysis, 83% of those getting once-daily therapy and 78.2% of those in the other arm had a clinical remission.
• In the intent-to-treat analysis, the rates were 79.1% and 75.7%, respectively.

Despite the lack of statistical significance, Dr. Kruis pointed out, "all the numbers were in favor of once-daily dosing."

The two dosing levels also did not differ in terms of endoscopic remission, mucosal healing, or histological remission, Dr. Kruis reported.

For example, mucosal healing - defined as a disease activity index of one or less - was 80.6% for the once-daily group and 80.4% for the other arm among the per-protocol population. The rates were slightly lower, but still almost identical among the intent-to-treat population, he said.

The idea of once-daily dosing is the "way the field has been moving," according to Hillary Steinhart, M.D., of Toronto's University Health Network, who was co-chairman of the session.

Indeed, the current study comes only a few months after Lialda, another once-daily formulation of mesalamine, was approved by the FDA for marketing in the U.S. The Salofalk granules are not approved in the U.S.

"In terms of convenience, as well as improved patient adherence, (once-daily dosing) is something that would be useful for many patients," Dr. Steinhart said.

But he dismissed Dr. Kruis's suggestion that there was numerical advantage for the once-daily formulation. "Statistically, there was no difference," he said.