BUDESONIDE ENEMA FOR THE TREATMENT OF ACTIVE, DISTAL ULCERATIVE-COLITIS AND PROCTITIS - A DOSE-RANGING STUDY

Background & Aims: Budesonide is a highly potent topical glucocorticos teroid that is characterized by low systemic availability as a result of high first-pass hepatic metabolism. The aim of this study was to ev aluate the efficacy and safety of three doses of an enema preparation of budesonide in patients with active distal ulcerative colitis/procti tis. Methods: In a double-blind multicenter trial, 233 patients were r andomized to receive either a placebo enema or budesonide enema at a d ose of 0.5 mg/100 mt, 2.0 mg/100 mt, or 8.0 mg/100 mt. The primary eff icacy variables were an improvement of sigmoidoscopic inflammation gra de, total histopathology score, and remission rates. Effects on cortis ol concentrations were also assessed. Results: After 6 weeks of treatm ent, there was significant improvement in sigmoidoscopy and histopatho logy scores in the budesonide 2.0-mg and 8.0-mg dose groups compared w ith placebo. Remission was achieved in 19% of patients in the 2.0-mg b udesonide group (P less than or equal to 0.050) and 27% of patients in the 8.0-mg budesonide group (P less than or equal to 0.001) compared with 4% in the placebo group. More than 90% of all budesonide patients had a normal adrenocorticotropin (ACTH)stimulated cortisol response a t the last visit. The budesonide enemas were well tolerated. Conclusio ns: Budesonide enema is both effective and safe for the treatment of a ctive distal ulcerative colitis/proctitis. A dose of 2.0 mg/100 mt bud esonide is the lowest effective dose.