Novel Formulation of Mesalazine Induces Remission of Ulcerative Colitis
COPENHAGEN—A novel, once-daily, high-dose oral formulation of mesalazine (5-aminosalicyclic acid) may enhance the induction of remission in acute mild-to-moderate ulcerative colitis (UC), according to data from a trial released at the 13th United European Gastroenterology Week.
Lead investigator Michael A. Kamm, MD, chairman of medicine, and director, Physiology Unit, St. Mark’s Hospital, London, reported results from a phase 3 clinical trial investigating the new formulation, known as SPD476 (Shire Pharmaceuticals).
The current standard of care for the induction and maintenance of remission in UC is mesalazine,” Dr Kamm pointed out. “However, presently available oral formulations do not consistently deliver the active drug to the entire colon and require inconvenient, multiple daily dosing regimens, which may reduce patient compliance and efficacy and adversely affect overall treatment outcomes.” He added that SPD476 “provides delayed and extended delivery of the active drug to the entire colon, thereby creating the potential for once-daily administration.”
Dr Kamm and colleagues noted this new formulation may for the first time offer patients the possibility of once-daily mesalazine dosing; SPD476 utilizes Multi-Matrix System technology to provide the highest mesalazine doses per tablet and deliver delayed, extended medication consistently throughout the colon.
A total of 280 patients were randomized to 8 weeks of treatment with SPD476, 2.4 g/day (given as 1.2 g twice daily); SPD476, 4.8 g/day (given once daily); or placebo.
The primary end point was the percentage of patients who achieved remission at study completion. Remission was defined as a disease activity index (DAI) score of ≤1, along with a score of 0 for rectal bleeding and stool frequency, and at least a 1-point reduction from baseline in sigmoidoscopy score.
A significantly higher percentage of patients receiving the active regimens achieved remission than those receiving placebo: 29.2% in the SPD476 4.8 g/day group, 34.1% in the 2.4 g/day, twice daily, group, and 12.9% in the placebo group (P = .001).
The trial included patients aged ³18 years with a DAI score of 4 to 10 in whom UC had initially been diagnosed by sigmoidoscopy, colonoscopy, or a barium enema. Patients also had a history compatible with UC, a sigmoidoscopy score of at least 1, a physician’s global assessment of ≤2, and had a relapse within 6 weeks of entering the trial.
In addition to a significantly greater proportion of patients achieving remission after 8 weeks, both SPD476 dosing regimens were found to be superior to placebo for secondary end points. These included clinical improvement (a decrease in DAI of 3 points from baseline), clinical remission (complete resolution of symptoms), and sigmoidoscopic (mucosal) improvement from baseline.
There were no significant differences in the rate of side effects in the 3 groups.
Dr Kamm noted that there was a trend toward better clinical improvement in patients with once-daily versus twice-daily dosing as well as improved sigmoidoscopy scores and improved physician’s global assessments.
He concluded that SPD476 has the potential to provide effective treatment for acute mild- to-moderate, active UC in both left-sided and extensive disease using once-daily, high-concentration tablets. —J.S.