Budesonide versus prednisolone for the treatment of active Crohn's disease in children: a randomized, double-blind, controlled, multicentre trial. Budesonide as maintenance treatment in Crohn's disease: a placebo-controlled trial. Oral budesonide is as effective as oral prednisolone in active Crohn's disease. The Global Budesonide Study Group. Budesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study. Oral budesonide as maintenance therapy in Crohn's disease--results of a 12-month study. Global Budesonide Study Group. Oral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Canadian Inflammatory Bowel Disease Study Group. A comparison of budesonide with prednisolone for active Crohn's disease. Budesonide versus prednisone in the treatment of active Crohn's disease. The Israeli Budesonide Study Group. A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease. Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group. Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States.
Budesonide is a corticosteroid with low systemic bioavailability because of its high first-pass metabolism in the liver. In this paediatric, randomized, double-blind, double-dummy, controlled, multicentre trial, the safety and efficacy of budesonide versus prednisolone were evaluated in children with active Crohn's disease.
                Forty-eight children, aged 6-16 years, with active Crohn's disease (Crohn's Disease Activity Index > 200) involving ileum and/or ascending colon were randomized to receive budesonide (9 mg/day for 8 weeks, 6 mg/day for 4 weeks) or prednisolone (1 mg/kg/day for 4 weeks, tapering for 8 weeks).
                The groups were comparable for age, sex, pubertal stage, disease activity and disease duration. Mean morning plasma cortisol concentration was significantly higher in the budesonide group (200 nmol/l) than in the prednisolone group (98 nmol/l) after 8 weeks, reflecting less adrenal suppression by budesonide (difference -102 nmol/l; 95% CI -226, -52; P = 0.0028). Glucocorticosteroid side effects such as moon face and acne occurred significantly less frequently in the budesonide group. Remission (Crohn's Disease Activity Index < or = 150) was seen at 8 weeks in 12/22 (55%) patients treated with budesonide and in 17/24 (71%) patients receiving prednisolone (difference -16%; 95% CI -45,13; P = 0.25).
                Significantly fewer side effects and less adrenal suppression were observed in the children receiving budesonide. Remission rates were not significantly different in the two groups. However, there was a trend for prednisolone to be more effective for inducing remission. To assess the efficacy and safety of budesonide capsules 6 mg daily for prolongation of time to relapse and maintenance of remission in patients with Crohn's disease (CD) affecting the ileum and/or ascending colon.
                In a double-blind, placebo-controlled, multicentre trial, 110 patients with CD, who had previously achieved remission in a placebo-controlled trial of budesonide 9 mg daily, were randomly assigned to receive budesonide 6 mg once daily or placebo for 52 weeks. Primary outcome measure was time to relapse [CD activity index (CDAI) of >150 plus an increase of at least 60 points from study entry or withdrawal due to clinical deterioration].
                Median time to relapse was 360 days for budesonide patients; 169 days for placebo patients (P = 0.132). No significant differences were seen between groups in relapse rates at 1 year. Budesonide was safe and well tolerated, with a similar adverse events profile to placebo.
                Patients treated with budesonide 6 mg once daily had a trend towards a prolonged time to relapse and lower CDAI scores compared with patients treated with placebo, but relapse rates were not significantly different at the 1-year end point. The use of corticosteroids in active Crohn's disease often becomes limited by side effects. Budesonide is a potent corticosteroid with low systemic bioavailability due to an extensive first pass liver metabolism.
                To compare the efficacy and safety of two dosage regimens of budesonide and prednisolone in patients with active Crohn's disease affecting the ileum and/or the ascending colon.
                One hundred and seventy eight patients were randomised to receive budesonide controlled ileal release (CIR) capsules 9 mg once daily or 4.5 mg twice daily, or prednisolone tablets 40 mg once daily. The treatment period was 12 weeks. The primary efficacy variable was clinical remission, defined as a Crohn's Disease Activity Index (CDAI) of 150 or less.
                After eight weeks of treatment, remission occurred in 60% of patients receiving budesonide once daily or prednisolone and in 42% of those receiving budesonide twice daily (p = 0.062). The presence of glucocorticoid associated side effects was similar in all groups; however, moon face was more common in the prednisolone group (p = 0.0005). The highest frequency of impaired adrenal function, as measured by a short ACTH test, was found in the prednisolone group (p = 0.0023).
                Budesonide CIR, administered at 9 mg once daily or 4.5 mg twice daily, is comparable to prednisolone in inducing remission in active Crohn's disease. The single dose administration is as promptly effective as prednisolone and represents a simpler and safer therapeutic approach, with a considerable reduction in side effects. To evaluate the efficacy and safety of the topical corticosteroid budesonide, given in an oral controlled release formulation for maintenance of remission in patients with ileal and ileocaecal Crohn's disease (CD).
                Out of 176 patients with active CD who had achieved remission (CD activity index score < or = 150) after 10 weeks' treatment with either budesonide or prednisolone, 90 were randomised to continue with once daily treatment of 6 mg budesonide, or 3 mg budesonide or placebo for up to 12 months in a double blind, multicentre trial. Time to symptomatic relapse was calculated using Kaplan-Meier estimates. Morning plasma cortisol was measured at clinic visits and a corticotropin stimulation test was performed after three months of treatment.
                Thirty two patients were allocated to the 6 mg budesonide group, 31 to the 3 mg group, and 27 to the placebo group. After three months, 19 per cent of the patients in the 6 mg group had relapsed, compared with 45 per cent in the 3 mg group and 44 per cent in the placebo group (p = 0.047). The corresponding results after 12 months was 59 per cent in the 6 mg budesonide group, 74 per cent in the 3 mg group, and 63 per cent in the placebo group (p = 0.44). The median time to relapse or discontinuation was 258 days in the 6 mg group, 139 days in the 3 mg group, and 92 days in the placebo group (p = 0.021). Mean morning plasma cortisol values increased from entry in all three groups with no statistically significant differences at 12 months. All 13 patients remaining in the placebo group after three months had a normal corticotropin stimulation response, compared with 18 of 23 patients in the 6 mg, and 19 of 21 in the 3 mg budesonide groups (p = 0.14). Acne and moon face were slightly more common in the budesonide groups.
                6 mg budesonide once daily is significantly more efficacious than placebo in prolonging time to relapse in CD, and causes only minor systemic side effects. Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid inactivation. We have assessed the efficacy and safety of an oral controlled ileal release (CIR) preparation of budesonide for maintenance of remission in patients with ileal or ileocaecal Crohn's disease.
                In a double-blind, multicentre trial, 75 patients in clinical remission (Crohn's Disease Activity Index, CDAI, < or = 150) were randomly assigned to receive placebo, budesonide 3 mg or budesonide 6 mg daily for 12 months. Trial drugs were given at a fixed dose and without concomitant medication. The primary outcome measure was relapse, defined as a CDAI > 150 together with an increase of at least 60 units from entry. A patient was also considered to have a relapse if withdrawn from the study due to clinical deterioration, whether or not a CDAI value could be calculated at that time.
                There were no statistically significant differences in the relapse rate at any time-point throughout the study. By 12 months the proportion of patients having relapsed were 48, 46 and 60% in those patients treated with budesonide 6 mg, 3 mg and placebo, respectively (N.S.). Treatments were well tolerated, and the proportion of patients with suppressed adrenal function (according to predetermined criteria) were 50% (6 mg), 26% (3 mg) and 17% (placebo) (P = 0.096).
                In the present study, relapse rate and time to relapse were similar in the patients treated with budesonide CIR, 6 mg daily or 3 mg daily or with placebo, throughout 12 months. This is in contrast to the two previous trials with identical design, where a significant effect of budesonide CIR in prolonging the median time to relapse was found. Possible reasons for the negative results of the present study include small sample size, and the fact that there was a high placebo response. Budesonide is a corticosteroid with high topical anti-inflammatory activity and low systemic activity due to rapid hepatic metabolism. The efficacy and safety of an oral controlled-release preparation of budesonide for maintenance of remission was evaluated in patients with ileal or ileocecal Crohn's disease.
                In a double-blind, multicenter trial, 105 patients were randomly assigned to receive placebo or budesonide at doses of 3 or 6 mg daily for 1 year. The primary outcome measure was relapse defined by a Crohn's Disease Activity Index score of > 150 and a minimum increase of 60 points.
                Patients receiving 6 mg of budesonide had a median time to relapse or discontinuation of therapy of 178 days compared with 124 days in those receiving 3 mg of budesonide and 39 days in those receiving placebo. However, at 1 year, the rate of relapse in the group receiving 6 mg of budesonide was similar to the rates in the 3-mg and placebo groups. Basal plasma cortisol levels and incidence of corticosteroid-associated effects were similar in the three groups.
                Oral controlled-release budesonide (6 mg/day) was well tolerated and prolonged remission in Crohn's disease of the ileum and proximal colon, but this effect was not sustained at 1-year follow-up. Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low.
                We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week.
                At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score < or = 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisolone (P = 0.12). The mean score on the Crohn's disease activity index decreased from 275 to 175 in the budesonide group and from 279 to 136 in the prednisolone group (P = 0.001). Corticosteroid-associated side effects were significantly less common in the budesonide group (29 vs. 48 patients, P = 0.003). Two patients in the prednisolone group had serious complications (one had intestinal perforation and one an abdominal-wall fistula). The mean morning plasma cortisol concentration was significantly lower in the prednisolone group than in the budesonide group after 4 weeks (P < 0.001) and 8 weeks (P = 0.02) of therapy, but not after 10 weeks.
                Among patients with active Crohn's disease, both controlled-release budesonide and prednisolone are effective in inducing remission. In this trial, prednisolone reduced scores on the Crohn's disease activity index more, whereas with budesonide there were fewer glucocorticoid-associated side effects and less suppression of pituitary-adrenal function. Budesonide (BUD) is a potent steroid that undergoes extensive first-pass metabolism. BUD incorporated in a pH-dependent formulation has been proposed as an alternative treatment for Crohn's disease (CD). The aim of this study was to compare the efficacy and safety of BUD and prednisone (PRED) in the treatment of active CD involving the terminal ileum and/or the colon.
                Patients with mild to moderately active CD were included in a randomized, double-blind, double-dummy controlled trial. Patients received either 9 mg BUD once daily for 8 weeks or 40 mg PRED once daily for the first 2 weeks tapered gradually to 5 mg/day by the end of the study. Disease activity, quality of life, and laboratory parameters were recorded.
                One hundred patients received BUD, and 101 patients received PRED. By intention-to-treat analysis, treatment efficacy defined as Crohn's Disease Activity Index of <150 at completion was 51% and 52.5% for the BUD and PRED groups, respectively. Twice as many responded to treatment with no side effects in the BUD compared with the PRED group (30% vs. 14%) (P = 0.006). Most of the decrease in CDAI scores occurred during the first 2 weeks.
                BUD is as effective as PRED in the treatment of CD involving the terminal ileum and right colon. BUD has significantly fewer steroid-related adverse reactions. Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease.
                A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease.
                Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01).
                Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity. Endoscopic recurrence of Crohn's disease frequently occurs within weeks after 'curative' operation. Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence.
                A multicentre randomized double-blind placebo-controlled trial of 1 year duration was performed.
                Departments of surgery, endoscopy and pathology of three university hospitals participated in the trial.
                Patients with Crohn's disease who underwent ileal and/or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study. Of the 88 randomized patients, 83 patients were included in the efficacy analysis (budesonide n = 43, placebo n = 40). Treatment was started within 2 weeks after surgery.
                Colonoscopy was performed 3 and 12 months postoperatively. The anastomosis and the adjacent bowel were evaluated by endoscopy and histology. For follow-up of the clinical course of the disease the Crohn's disease activity index (CDAI) was used.
                The primary outcome variable was recurrence of Crohn's disease based on endoscopic findings. Secondary efficacy variables were histology scores, CDAI, time-to-failure and global judgement of well-being of the patient.
                The recurrence rate after 1 year (endoscopic and/or clinical) was 57% (20/35) in the budesonide group and 70% (19/27) in the placebo group (n.s.). Mean time-to-failure was 196 days under budesonide and 154 days under placebo (n.s.). Median CDAI (relapse 19% vs. 28%) and global patients' judgement at the end of treatment (bad 5% vs. 15%) was slightly in favour of budesonide. One patient in each group discontinued the trial because of adverse events. Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group (32% vs. 17%) (n.s.).
                Although the effect of budesonide was altogether positive in almost all variables studied in this trial (e.g. endoscopic and histopathological score, time-to-failure, CDAI, patients' global judgement and rate of side effects), this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant. According to these results, low-dose oral budesonide cannot be recommended to be used for the prevention of postoperative relapse in Crohn's disease. Budesonide controlled ileal release (CIR) capsules deliver budesonide, a glucocorticosteroid with high topical and low systemic activity, to the distal ileum and the proximal colon. In four previous controlled trials in Crohn's disease, remission rates ranged from 51% to 69%. We sought to evaluate the efficacy and safety of this drug in a population of patients in the United States with Crohn's disease.
                In this multicenter, double blind, randomized trial, 200 patients in the United States with mild to moderate Crohn's disease (Crohn's Disease Activity Index [CDAI] between 200 and 450) involving the distal ileum and/or ascending colon received 9 mg of budesonide CIR once daily, 4.5 mg b.i.d., or placebos for 8 wk. The primary outcome was remission defined by a CDAI of 150 or less.
                Remission was achieved in 48%, 53%, and 33% with 9 mg once daily, 4.5 mg b.i.d., and placebos, respectively, after 8 wk of treatment. Differences between the groups were not significant. The differences in mean change from baseline CDAI between the combined budesonide and placebo groups was significant (p < 0.05). There was no difference in observed adverse events between treatment groups, although a modest decrease in plasma cortisol levels was observed relative to the placebo (p < 0.01).
                Treatment of symptomatic Crohn's disease with budesonide CIR capsules (9 mg daily) was safe, and remission rates were similar to those achieved in previous trials. Although the remission rate did not significantly differ from the placebo response in this study, there was a significant change in the mean CDAI from baseline in the combined treatment groups relative to the placebo.
Budesonide is not more effective than placebo or weaning prednisolone for maintenance of remission in Crohn's disease. Some modest benefits are noted in patients receiving budesonide compared with placebo in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide. Therefore, budesonide is not recommended for maintenance of remission in Crohn's disease.