Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A₂, cyclooxygenase-2 (COX-2), and NF-κB (Nuclear factor kappa B), curbing the inflammatory response.

Prednisone, methylprednisolone, and hydrocortisone are the primary glucocorticoids used. Prednisone is almost exclusively given orally, and, while methylprednisolone and hydrocortisone can also be given orally, in severe cases they are given intravenously. These drugs target the entire gastrointestinal tract, inducing remission effectively, but have limitations for long-term use due to significant adverse effects such as skin thinning, cardiovascular events, and psychiatric disturbances.

Budesonide (Pulmacort), another glucocorticoid, is available in oral, rectal, and controlled-release formulations. Oral budesonide is used for ileocecal Crohn's disease, while rectal formulations are preferred for diseases limited to the rectum and left colon. It exhibits high first-pass hepatic metabolism, resulting in low systemic bioavailability and fewer side effects than conventional glucocorticoids. However, its efficacy in achieving clinical remission may be slightly lower than prednisolone.