Developments in the Treatment of Inflammatory Bowel Disease

Developments in the Treatment of Inflammatory Bowel Disease

Cohen Russell D
US Gastroenterology Review 2007 - Issue I - March 2007
Published: October 2008
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There have been multiple new treatments for inflammatory bowel disease (IBD) that have either emerged in the market within the past few years or are in development. This review will walk through the various medication classes and advances in therapies.

Aminosalicylates
The release of balsalazide disodium (Colazal® in the US; Colazide® in Europe; Salix Pharmaceuticals, Raleigh, North Carolina) in the US in the past few years has provided another option for patients for the treatment of ulcerative colitis. This unique product is a combination of 4-amino-benzoyl- β-alanine (4-ABA) connected by an azo-bond to mesalamine, resulting in a non-sulfa delivery system of mesalamine to the colon.1 One of the advantages over previous therapies is the absence of a sulfa moiety, as well as near complete delivery to the colon. Studies of efficacy included a headto- head trial showing superior remission rates with basalazide versus pH-release mesalamine (38% versus 12% at week four; 54% versus 22% at week eight, and 62% versus 37% at week 12; p<0.05) and shorter time to first asymptomatic day (median 10 versus 25 days; p=0.0039), suggesting that this formulation is more effective in certain individuals.2

Newly approved in January 2007 is SPD476 (Lialda™ in the US; Mezavant™ in Europe; Shire Pharmaceuticals Inc. Wayne, Pennsylvania). This formulation uses a patented multi-matrix system (MMX) whereby the mesalamine is incorporated into microparticles of a lipophilic matrix dispersed within a hydrophilic matrix.3 This in turn is coated by a gastroresistant polymer which breaks down at a pH of 7, typically thought to occur in the ileum. The intent is that this will allow for a controlledrelease, and delayed degradation of the mesalamine in the colon. This is the first mesalamine agent approved for once-a-day dosing. Furthermore, its 1.2g of mesalamine per pill is more than twice as high as most competitors, allowing for far fewer daily pills.

In the Pivotal 301 trial, SPD476 dosed at 2.4g given twice daily or 4.8g once daily was superior to placebo in clinical and endoscopic remission at eight weeks (34.1%, 29.2%, 12.9%, respectively; p<0.009 for either mesalamine versus placebo).4 In the other Pivotal 302 trial, once-a-day dosing of SPD476 at 2.4g or 4.8g was superior to placebo in clinical and endoscopic remission at eight weeks (40.5%, 41.2%. versus 22.1% respectively; p<0.01).5 The various event rates and study dropout rates were extremely low with the drug, consistent with what has been seen with other mesalamine products.

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