Newer pharmacologic agents for the therapy of inflammatory bowel disease.

ABSTRACT

Topical 5-ASA Agents. Observations that 5-ASA may be the clinically active component of sulfasalazine have stimulated extensive pharmaceutical efforts to develop a new class of agents for the treatment of the inflammatory bowel diseases. Both oral and rectal forms of 5-ASA have been designed, tested, and released for use in Europe and Canada. Only one rectal 5-ASA formulation is now commercially available in the United States. Studies with topical 5-ASA have demonstrated that this formulation is safe and effective for distal colitis, even in patients with disease refractory to standard therapy. Adverse effects of topical 5-ASA are minimal. However, optimal treatment doses have not been defined, relapse is common after withdrawal of therapy, and issues regarding maintenance regimens are not yet resolved. Other disadvantages include the expense and inconvenience of enema therapy. However, rectally administered 5-ASA is an appropriate initial therapy for the treatment of distal ulcerative colitis, or as a therapeutic option for refractory distal colitis. Data are insufficient to make recommendations regarding the use of topical 5-ASA in Crohn's disease. Whether this class of agents will be of benefit for Crohn's proctitis or for perineal disease must await further clinical trials. Oral 5-ASA Agents. There appears to be a well-substantiated benefit equivalent to that of sulfasalazine achieved by the new oral formulations of 5-ASA when used for the treatment of acute mild to moderate ulcerative colitis, and as maintenance treatment of ulcerative colitis in remission. Adverse reactions to these agents are uncommon, usually mild, and infrequently require withdrawal of therapy. The major problem reported with these agents is watery diarrhea, most commonly associated with olsalazine, but the practical importance of this adverse effect is disputed. Rare occurrences of reversible pericarditis and acute pancreatitis have been encountered during clinical application of these agents. As more experience is obtained, these agents may become the initial therapy of choice for the treatment of mild to moderate ulcerative colitis and for maintenance in inactive disease. Currently available data have defined a role for these agents as an important alternative for the treatment of patients intolerant or allergic to sulfasalazine. As with sulfasalazine, these agents should not be used as the sole treatment for severely active ulcerative colitis. Many unanswered questions remain regarding therapy with these agents for ulcerative colitis. Still undefined are optimal drug dosages, appropriate dosing intervals, and the necessary duration of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)