Glucocorticoids

Glucocorticoids are highly effective for the short- term control of Crohn's disease-related symptoms, but they are less effective for maintenance of remission, and have significant adverse effects that preclude safe long-term administration.

They work by interacting with glucocorticoid receptors in the cell nucleus to alter expression of inflammatory genes, inhibit the expression of adhesion molecules, and inhibit the migration of inflammatory cells into tissues.

In a 23-year population-based study of the natural history of Crohn's disease, the short-term benefit of steroids was substantial with 84 % of patients demonstrating complete or partial response at 30 days. However, only 32 % of these patients were able to maintain remission at the end of a year without ongoing steroid use.

Another 28 % were steroid dependent and 39 % required surgery by 1 year. This study highlights the excellent short-term efficacy of steroids but also underscores the need for steroid-sparing therapy to maintain the initial response to steroids.

Several other studies have confirmed the efficacy of Medical Therapy for systemic glucocorticoids for induction of remission in active Crohn's disease.

Despite their benefit for induction of remission, systemic glucocorticoids have numerous adverse effects that prohibit sustained administration. Short-term side effects can include psychiatric disturbances such as anxiety, emotional lability, psychosis, and insomnia.

Other potential effects can include hypertension, hyperglycemia, acne, fungal, viral, and bacterial infections, and weight gain. Long-term effects can include cataracts, glaucoma, osteoporosis, avascular necrosis, diabetes mellitus, steroid induced myopathy, and adrenal insufficiency. In a safety registry of Crohn's disease patients, corticosteroid use was independently associated with higher risk of mortality (HR 2.14) and serious infection (HR 1.57).

Because of the multiple side effects associated with these medications, budesonide has been studied as an alternative glucocorticoid treatment.

Budesonide is a topical glucocorticoid with high affinity for the glucocorticoid receptors (200 times that of prednisolone) that delivers steroid locally to the distal ileum and proximal colon. Because of extensive first pass metabolism in the liver, only 10- 15 % of the oral dose is systemically active, leading to fewer side effects compared with traditional glucocorticoids.

Abnormal responses to ACTH tests were less common in budesonide-treated patients compared to those receiving systemic glucocorticoids, but still more common than in patients receiving placebo, confirming there is a small degree of systemic activity with budesonide. Budesonide is more effective than placebo but less effective than prednisone in inducing remission in patients with active luminal Crohn's disease, and the greatest benefit appears to be in patients with ileal or proximal colonic disease. Budesonide is not effective for the prevention of relapse in patients with quiescent Crohn's disease.