Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors

ABSTRACT

Objectives: A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission.

Methods: Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC–related adverse event (AE).

Results: Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%).

Conclusion: Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

KEYWORDS:

• Inflammatory bowel disease
• ulcerative colitis
• mesalamine
• remission

Financial and competing interests disclosure

This study and trials MPUC3003 and MPUC3004 were supported by Salix, a Division of Valeant Pharmaceuticals North America LLC, Bridgewater, NJ, USA. Technical editorial and medical writing assistance, under the direction of the authors, was provided by Synchrony Medical Communications, LLC (West Chester, PA, USA) and funded by Salix. SF Zakko serves as a principal investigator on several studies sponsored by Salix. He is also a consultant and speaker for the company, and is a recipient of grants from the company. Additionally, he is a consultant, speaker, and investigator for Novartis, Pfizer, and GlaxoSmithKline. GL Gordon serves as principal investigator on a variety of research protocols for Salix; serves as a consultant to and on the speakers’ bureau for AbbVie, Aptalis, Janssen Pharmaceuticals, Inc., Prometheus, Salix, Sanofi-Aventis U.S., Takeda Pharmaceutical Company Limited, UCB, and Warner Chilcott; and receives research grants from AbbVie, Aptalis, Avaxia, Coronado, Cubist, Dr. Falk, Evoke, Ferring, Furiex, GlaxoSmithKline, Hutchinson, Janssen Pharmaceuticals, Inc., Lexicon, Pfizer Inc., Prometheus, Red Hill BioPharma, Revogenex, Salix, Sanofi-Aventis U.S., Shire, Takeda Pharmaceutical Company Limited, Theravance, Tranzyme, UBC, UCB, Ventrus, and Warner Chilcott. AC Barrett, E Bortey, C Paterson and WP Forbes are former employees of Salix. GR Lichtenstein has served as a consultant for Abbott Corporation/AbbVie; Elan Corporation, plc; Hospira, Inc.; Millennium Pharmaceuticals, Inc.; Ono Pharmaceutical Co., Ltd.; Pfizer Inc.; Santarus, Inc., previously a subsidiary of Salix; Schering-Plough Corp.; and Takeda Pharmaceutical Company Limited. He has served as a research consultant for Alaven Pharmaceutical LLC; Ferring Pharmaceuticals; Janssen Ortho Biotech; Prometheus Laboratories Inc.; Salix; Shire plc; UCB, Inc.; and Warner Chilcott. Additionally, he has served as a researcher for Bristol-Myers Squibb Company and has received honoraria from Ironwood Pharmaceuticals, Inc., for participation in the company’s CME program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.