CORTICOSTEROID-THERAPY FOR IBD - OLD AND NEW

Corticosteroids remain the most effective treatment for die management of patients with acute inflammatory bowel disease (IBD). The superior efficacy of corticosteroids has been demonstrated when administered t opically for distal ulcerative colitis or systemically for pancolitis, and for active Crohn's disease of the small bowel alone or when combi ned with colonic disease. Notwithstanding the symptomatic benefit of p rednisone in active Crohn's disease, however, only a minority of patie nts achieve endoscopic remission. Corticosteroids have a broad range o f anti-inflammatory effects, including reductions of interleukin-I pro duction by macrophages and interleukin-II synthesis by lymphocytes, in hibition of platelet-activating factor and decreased margination of ne utrophils. At pharmacological doses, corticosteroids also induce the s ynthesis of lipomodulin which, in turn, blocks phospholipase A2 and so limits availability of arachidonate for the production of leukotriene s and prostaglandins. Because corticosteroid treatment is associated w ith significant side effects, new agents have been sought to achieve e quivalent efficacy but with a lower adverse event profile' This approa ch is predicated on structural changes to the basic hydrocortisone and molecule to achieve potent topical anti-inflammatory effects, suffici ent water and lipid solubility that allows dissolution within the inte stinal lumen and rapid high-first pass metabolism by the liver to prod ucts with little or no biologic activity. Three steroid preparations d ev-eloped for rectal administration include tixocortal pivalate, beclo methasone and budesonide. Controlled trials undertaken in patients wit h active distal ulcerative colitis indicate each of these products has equivalent or superior efficacy when compared with hydrocortisone and without reductions of serum cortisol. Two preparations, fluticasone a nd budesonide, have been developed for oral administration and prelimi nary studies suggest efficacy for both drugs in patients with active i leal Crohn's disease. The first pass corticosteroids are potentially p romising new therapeutic agents for the management of IBD.