COPENHAGEN — Doubling the dose of mesalazine increased the drug's efficacy for moderately active ulcerative colitis in an analysis of more than 400 patients enrolled in two separate trials.
The findings “prove that 4.8 g/day mesalazine produced a clinically meaningful and statistically significant benefit over the standard 2.4 g/day,” Stephen B. Hanauer, M.D., said at the 13th United European Gasteroenterology Week. “The results support starting treatment at the higher dose in patients with moderately active ulcerative colitis,” said Dr. Hanauer, professor of medicine and clinical pharmacology at the University of Chicago.
Both studies were sponsored by Procter and Gamble, which now markets a 400-mg formulation of mesalazine (Asacol) that is used in a 2.4- g/day regimen for patients with ulcerative colitis.
The results of each study alone, which enrolled patients with either mild or moderate disease, were unable to show statistically that a 4.8-g daily dose, given as six 800-mg tablets, was superior to the 2.4-g dosage. But the results suggested that the higher dosage was especially effective in patients with moderate active disease, leading to a new analysis combining data from both studies. Dr. Hanauer is a consultant and speaker for Procter & Gamble and also receives research support from the company.
The combined studies enrolled 687 patients, of whom 423 had moderate disease and were evaluable after 6 weeks of treatment. Among 223 patients treated with 2.4 g/day mesalazine, 58% had treatment success, compared with a 72% rate among 200 patients treated with 4.8 g/day, a statistically significant difference, reported Dr. Hanauer, who is also chief of the section of gastroenterology and nutrition at the University of Chicago.
Treatment success was defined as an improvement from baseline in physician's global assessment with improvement in at least one of four categories of clinical assessment: stool frequency, rectal bleeding, sigmoidoscopy findings, and patient's functional assessment. Among the over 200 patients with mild disease, the 2.4-g/day dosage led to treatment success in 41% of patients, while 34% had success on the 4.8-g/day regimen, a nonsignificant difference. The results indicate that it's specifically patients with moderate disease who benefit from the higher dose, Dr. Hanauer said. Both dosages had similar safety profiles and were well tolerated.
The 4.8-g dose was clearly superior, but its advantage over lower dosages was “marginal,” suggesting the impact of boosting the dose levels off at 4.8 g/day and little would probably be gained by raising the dose further, he said. The FDA told Procter & Gamble last summer that the 800-mg formulation was approvable for ulcerative colitis; the company and the agency are resolving final issues before approval is granted.