In clinical trial results that surprised even the investigators, delayed-release mesalamine (Asacol HD, Procter & Gamble) once a day was as effective as a twice-a-day regimen in keeping ulcerative colitis (UC) inactive.
Once-a-day dosing also made for much higher compliance rates in patients, according to findings of the QD Dosing Investigation for Efficacy in UC Maintenance (QDIEM) study, the largest UC study undertaken to date. Results were announced here at the American College of Gastroenterology 2009 Annual Scientific Meeting in a late-breaking session.
"We were a little surprised at the results since delayed-release mesalamine is more of a bolus in the terminal ileum and right colon, so it wasn't clear that it could be administered once daily," first author and coinvestigator William J. Sandborn, MD, professor of medicine and gastrointestinal research, Mayo Clinic College of Medicine, and vice chairman, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, commented in an interview with Medscape Gastroenterology.
Dr. Sandborn continued, "A clinical trial was required to determine the answer to this question, and the QDIEM trial provided a definitive answer."
There were 1023 patients in QDIEM who had been in remission for at least 4 months before the start of the study (Simple Clinical Colitis Activity Index score < 2 points) on mesalamine doses ranging from 1.6 to 2.4 g a day. Patients were randomly assigned to either a once- or twice-daily dosing regimen at the same total daily dose that the patient had been maintained on before study entry, such that 70% received 2.4 g mesalamine daily, 28% received 1.6 g mesalamine daily, and 2% received 2.0 g mesalamine daily.
The primary endpoint was maintenance of remission at 6 months on a once-daily dosing regimen compared with twice-daily dosing. Relapse was defined as an Simple Clinical Colitis Activity Index score higher than 5 points. Patients who had not relapsed were considered to be in remission.
The time to relapse was similar between once-daily and twice-daily dosing (hazard ratio, 1.19; 95% confidence interval, 0.77 – 1.82). Serious adverse reactions and subsequent trial withdrawals resulting from adverse events were similar between the 2 groups.
Dr. Sanborn's team found that once-daily dosing with delayed-release mesalamine at doses of 1.6 to 2.4 g daily (administered in 400-mg tablets) was as effective as twice-daily dosing for maintenance of remission in patients with UC.
"Clinicians could use these data as a basis for administering delayed-release mesalamine as maintenance therapy at doses up to 2.4 g a day," said Dr. Sandborn.
"We saw significant differences in medication adherence up through 3 months, but not beyond," Dr. Sandborn noted. "However, when we asked patients if they preferred to take their medication once daily, a majority (58%) said they were extremely satisfied at month 12 with once-daily dosing."
"This was the most important study to come out of the 2009 [meeting]," asserted Jean-Paul Achkar, MD, FACG, chair of the educational affairs committee of the American College of Gastroenterology and a member of the Department of Gastroenterology at the Digestive Disease Center, The Cleveland Clinic, Ohio, in an interview with Medscape Gastroenterology: "On the surface, this may not sound very exciting, but patient adherence had been an important issue; we realize that patients don't take medications as they should, so having a simplified regimen of once-daily dosing is likely to improve compliance."
He added: "Currently, the US Food and Drug Administration has approved mesalamine at a dose of 2 pills, 3 times a day. Many of us in practice thought that was not practical, and many of us have cut down that dose to 2 divided doses, and this study is further evidence that we can back off further and go to once-daily dosing."
The study received research support from Procter & Gamble Pharmaceuticals, the maker of Asacol. Dr. Sandborn is a consultant for Procter & Gamble Pharmaceuticals. Dr. Achkar has disclosed no relevant financial relationships.
American College of Gastroenterology 2009 Annual Scientific Meeting: Abstract 39. Presented October 27, 2009.
Medscape by Kristina Rebelo, 11/3/09