Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial.

BACKGROUND: Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. METHODS: An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). RESULTS: The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. CONCLUSIONS: Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease.

Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test.

AIM: To study intestinal permeability (IP) and its relationship to the disease activity in patients with inflammatory bowel diseases (IBD) - Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Fifty-eight patients with active IBD (32 with CD and 26 with UC) and 25 healthy controls consented to participate in the study. The clinical activity of CD was estimated using the Crohn's Disease Activity Index (CDAI), and the endoscopic activity of UC using the Mayo scoring system. IP was assessed by the rise in levels of iohexol, which was administered orally (25 mL, 350 mg/mL) 2 h after breakfast. Three and six hours later serum (SIC mg/L) and urine (UIC g/mol) iohexol concentrations were determined by a validated HPLC-UV technique. RESULTS: In the CD group, SIC values at 3 h (2.95 ± 2.11 mg/L) and at 6 h after ingestion (2.63 ± 2.18 mg/L) were significantly higher compared to those of healthy subjects (1.25 ± 1.40 mg/L and 1.11 ± 1.10 mg/L, respectively, P < 0.05). UIC (g/mol) values were also higher in patients, but the differences were significant only for UIC at 6 h. Significant positive correlation (P < 0.05) was found between the CDAI and IP, assessed by SIC at 3 h (r = 0.60) and 6 h (r = 0.74) after the ingestion. In comparison to controls, SIC and UIC of UC patients were higher in the two studied periods, but the differences were significant at 6 h only. Significantly higher values of SIC (P < 0.05) were found in patients with severe endoscopic activity of UC compared to those of patients with mild and moderate activity (3.68 ± 3.18 vs 0.92 ± 0.69 mg/L). CONCLUSION: Serum levels of iohexol at 3 h and 6 h after its ingestion reflect increased IP, which is related to the disease activity in patients with IBD.