Intest Res.  2016 Jan;14(1):50-59. 10.5217/ir.2016.14.1.50.

Efficacy and safety of two pH-dependent-release mesalamine doses in moderately active ulcerative colitis: a multicenter, randomized, double-blind, parallel-group study

• Suzuki Y
• Iida M
• Ito H
• Saida I
• Hibi T

• KMID: 2174510
• DOI: http://doi.org/10.5217/ir.2016.14.1.50

Abstract

BACKGROUND/AIMS
The therapeutic effect of mesalamine is considered to be dose-dependent; however, no consensus has been reached regarding the optimal doses for individual patients. This study aimed to provide new insight for dose optimization using two doses of pH-dependent release mesalamine for induction of remission of moderately active ulcerative colitis (UC).
METHODS
In a multicenter, double-blind, randomized study, 110 patients with moderately active UC were assigned to two groups after treatment with a constant dose of mesalamine. Fifty-five patients were treated with a pH-dependent release formulation of 3.6 or 4.8 g/day for 8 weeks. The primary endpoint was a decrease in the UC disease activity index (UCDAI) adjusted by covariates.
RESULTS
In the full analysis set (n=110), the mean decrease in UCDAI was 3.1 in the 3.6 g/day group and 3.4 in the 4.8 g/day group (P>0.05). In a subgroup analysis, the effectiveness of the 4.8 g/day dose was greater in particular populations, such as those who had been previously treated with a lower dose of mesalamine and those with more severe disease. The safety was comparable between the two groups.
CONCLUSIONS
The results suggest that treatment with pH-dependent release mesalamine at either 3.6 or 4.8 g/day was effective and safe for the induction of remission in patients with moderately active UC. However, the patients receiving mesalamine at 2.4 g/day but in whom the therapeutic effect is not sufficient and having more severe symptoms (UCDAI 9-10), benefit from higher doses of mesalamine compared to others.

Keyword

Asacol; pH-dependent-release mesalamine; Colitis, ulcerative; Double-blind method

MeSH Terms

Colitis, Ulcerative*
Consensus
Double-Blind Method
Humans
Mesalamine*
Remission Induction
Ulcer*
Mesalamine

Figure

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  Fig. 1 Enrollment, randomization, and analysis of the study subjects. SAF, safety analysis set; FAS, full-analysis set; PPS, per-protocol set.

Reference

1. Kornbluth A, Sachar DB. Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology Practice Parameters Committee. Am J Gastroenterol. 2004; 99:1371–1385. PMID: 15233681.

2. Carter MJ, Lobo AJ, Travis SP;, British Society. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004; 53(Suppl 5):V1–V16. PMID: 15306569.

3. Feagan BG, Macdonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2012; 10:CD000543. DOI: 10.1002/14651858.CD000543.pub3. PMID: 23076889.

4. Friedman S, Blumberg RS. Inflammatory bowel disease. In : Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 16th ed. New York: McGraw-Hill;2004. p. 1776–1789.

5. Friedman S, Blumberg RS. Inflammatory bowel disease. In : Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison's principles of internal medicine. 18th ed. New York: McGraw-Hill;2011. p. 2477–2495.

6. Hanauer SB, Sandborn WJ, Dallaire C, et al. Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared to 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial. Can J Gastroenterol. 2007; 21(12):827–834. PMID: 18080055.

7. Hanauer SB, Sandborn WJ, Kornbluth A, et al. Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: The ASCEND II trial. Am J Gastroenterol. 2005; 100:2478–2485. PMID: 16279903.

8. Sandborn WJ, Regula J, Feagan BG, et al. Delayed-release oral mesalamine 4.8 g/day (800-mg) tablet is effective for patients with moderately active ulcerative colitis. Gastroenterology. 2009; 137:1934–1943. PMID: 19766640.

9. Hiwatashi N, Suzuki Y, Mitsuyama K, et al. Clinical trial: Effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study. J Gastroenterol. 2011; 46:46–56. PMID: 20878425.

10. Ito H, Iida M, Matsumoto T, et al. Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study. Inflamm Bowel Dis. 2010; 16:1567–1574. PMID: 20049950.

11. In : Hirai F, editor. Mayo score. Disease activity index of inflammatory bowel disease. Research Group for Intractable Inflammatory Bowel Disease (Watanabe Group). Health and labour science research grants from the Japanese Ministry of Health, Labour and Welfare and research on measures for intractable disease; 2007–2009 research report. 2010. p. 640.