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 topically for distal ulcerative colitis or systemically for pancolitis, and for active Crohn's disease of the small bowel alone or when combined with colonic disease. Notwithstanding the symptomatic benefit of prednisone in active Crohn's disease, however, only a minority of patients achieve endoscopic remission. Corticosteroids have a broad range of anti-inflammatory effects, including reductions of interleukin-I production by macrophages and interleukin-II synthesis by lymphocytes, inhibition of platelet-activating factor and decreased margination of neutrophils. At pharmacological doses, corticosteroids also induce the synthesis of lipomodulin which, in turn, blocks phospholipase A2 and so limits availability of arachidonate for the production of leukotrienes and prostaglandins. Because corticosteroid treatment is associated with significant side effects, new agents have been sought to achieve equivalent efficacy but with a lower adverse event profile' This approach is predicated on structural changes to the basic hydrocortisone and molecule to achieve potent topical anti-inflammatory effects, sufficient water and lipid solubility that allows dissolution within the intestinal lumen and rapid high-first pass metabolism by the liver to products with little or no biologic activity. Three steroid preparations dev-eloped for rectal administration include tixocortal pivalate, beclomethasone and budesonide. Controlled trials undertaken in patients with 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 and budesonide, have been developed for oral administration and preliminary studies suggest efficacy for both drugs in patients with active ileal Crohn's disease. The first pass corticosteroids are potentially promising new therapeutic agents for the management of IBD.