Once-Daily Dosing of Delayed-Release Oral Mesalamine (400-mg Tablet) Is as Effective as Twice-Daily Dosing for Maintenance of Remission of Ulcerative Colitis
Background & Aims
The practice of dosing mesalamines in divided doses for the treatment of ulcerative colitis (UC) began with sulfasalazine and was driven by sulfapyridine toxicity. This convention and the assumption that dosing multiple times a day is necessary to treat UC had not been challenged until recently. This study was conducted to determine the efficacy and safety of once-daily dosing of delayed-release mesalamine (Asacol 400-mg tablets) compared with twice-daily dosing for maintaining remission in UC patients.
Methods
A multicenter, randomized, investigator-blinded, 12-month, active-control trial was conducted to assess the noninferiority of delayed-release mesalamine 1.6–2.4 g/day administered once daily compared with twice daily in patients with mild-to-moderate UC currently in clinical remission. The primary end point was maintenance of clinical remission at month 6.
Results
A total of 1023 patients were randomized and dosed. The primary objective of noninferiority was met. At month 6, 90.5% of patients receiving once-daily dosing had maintained clinical remission, compared with 91.8% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -2.3 to 4.9). At month 12, 85.4% of patients receiving once-daily dosing had maintained clinical remission, compared with 85.4% of patients receiving twice-daily dosing (95% confidence interval for twice daily - once daily, -4.6 to 4.7). Both regimens had low rates of withdrawals as a result of adverse events and serious adverse events.
Conclusions
Once-daily dosing of delayed-release mesalamine at doses of 1.6–2.4 g/day was shown to be as effective as twice-daily dosing for maintenance of clinical remission in patients with UC.
Keywords: Ulcerative Colitis, Mesalamine, Maintenance, Controlled Trial
Abbreviations used in this paper: CI, confidence interval, MARS, Medication Adherence Report Scale, QDIEM, QD Dosing Investigation for Efficacy in UC Maintenance, SAE, serious adverse event, SCCAI, Simple Clinical Colitis Activity Index
This article has an accompanying continuing medical education activity on page e11. Learning Objective: Upon completion of reading this article, successful learners will become familiar with the comparative efficacy of once-daily dosing of delayed-release mesalamine as compared with divided dosing in patients with ulcerative colitis.
Conflicts of interest These authors disclose the following: William Sandborn has served as a consultant for and received research funding from Procter & Gamble Pharmaceuticals, Inc, and Shire Pharmaceuticals, and has served as a consultant for Salix Pharmaceuticals, Inc; Joshua Korzenik has served as a consultant for Procter & Gamble Pharmaceuticals, Shire, CytokinePharma, Eurand, Zyogenetics, and received research funding from Procter & Gamble Pharmaceuticals; Bret Lashner has served on the Advisory Board/Speakers Bureau for Procter & Gamble Pharmaceuticals, Salix, Shire, UCB, Abbott, and Prometheus; Jonathan Leighton has served as a consultant for Procter & Gamble Pharmaceuticals and received research funding from Procter & Gamble Pharmaceuticals, Abbott, Bristol Myers Squibb, Otsuka, and Centocor; Uma Mahadevan has served as a consultant for Procter & Gamble Pharmaceuticals and Shire; James F. Marion has served as a consultant for Procter & Gamble Pharmaceuticals and has served on the Speakers Bureau for Procter & Gamble Pharmaceuticals, Shire, and UCB; Michael Safdi has received research funding from Forest Research Institute, Conatus, Shire, Tibotec, Millennium, Cosmo, Abbott, Centocor, Pfizer, Elan, Procter & Gamble Pharmaceuticals, Salix Pharmaceuticals, Biolex, Gilead, Roche, Vertex, Celltech, Eisai, BMS, and Lexicon, has served as a consultant for Procter & Gamble Pharmaceuticals, and has served on the Speakers Bureau for Procter & Gamble Pharmaceuticals, Shire, and Centocor; Charles A. Sninsky has served on Advisory Boards and Speakers Bureau for Procter & Gamble Pharmaceuticals, Shire, Centocor, Abbott, UCB, and Prometheus; Keith A. Friedenberg owns shares of Procter & Gamble stock; Preston Dunnmon and David Ramsey are employees of Procter & Gamble Pharmaceuticals; and Sunanda Kane has served as a consultant for and received research funding from Procter & Gamble Pharmaceuticals and Shire. The remaining authors disclose no conflicts: Raman M. Patel.
Funding This study was funded by Procter & Gamble Pharmaceuticals, Inc, Mason, Ohio. ClinicalTrials.gov Identifier NCT00505778.
View this article's video abstract at www.gastrojournal.org.
PII: S0016-5085(10)00006-5
doi:10.1053/j.gastro.2009.12.054
© 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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