Background: Corticosteroids remain one of the most popular medication choices for the induction of remission in ulcerative colitis and Crohn's disease. While corticosteroids may improve symptoms, they do not always result in mucosal healing and have significant adverse effects. Steroids which act topically, with less systemic side-effects may be more desirable. Oral budesonide, a topically acting corticosteroid with extensive first pass hepatic metabolism, is effective in Crohn's disease and in enema formulation for left-sided ulcerative colitis. Data are limited regarding the role of oral budesonide in ulcerative colitis.
Objectives: To systematically review the safety and efficacy of oral budesonide for induction of remission in ulcerative colitis.
Search strategy: Electronic searching of the MEDLINE and EMBASE databases was performed. Two authors independently reviewed all identified titles and abstracts. Full text articles of all potentially relevant studies were retrieved. Reference lists of review articles were searched in an attempt to identify additional studies. Abstracts of the major gastroenterology scientific meetings, held over the past 3 years, were hand searched. The ClinicalTrials.gov website as well as the Cochrane Registry of Controlled Trials was searched to identify any ongoing trials. Direct communication with pharmaceutical manufacturers was established to identify any ongoing or unpublished studies.
Selection criteria: Randomized controlled trials of oral budesonide for the induction of remission in ulcerative colitis, with either a parallel arm or cross-over design, were considered eligible for inclusion. There were no exclusions based on patient age or the type, dose or duration of budesonide therapy. The primary outcome was the induction of clinical remission in ulcerative colitis. Secondary outcomes included clinical, histologic and endoscopic improvement, endoscopic mucosal healing, change in disease activity index scores, adverse events and study withdrawals.
Data collection and analysis: Studies were reviewed for eligibility, data were extracted and quality assessed by 2 independent investigators. It was not possible to perform a meta-analysis of the included studies due to significant heterogeneity, with each study comparing budesonide to a different control medication.
Main results: Three studies met the inclusion criteria. Oral budesonide was significantly less likely to induce clinical remission than oral mesalamine after 8 weeks of therapy (RR 0.72, 95% CI 0.57 to 0.91). There was no significant benefit of oral budesonide in comparison to placebo for inducing clinical remission after 4 weeks of treatment (RR 1.41, 95% CI 0.59 to 3.39). A small pilot study reported no statistically significant difference in endoscopic remission between budesonide and prednisolone (RR 0.75, 95% CI 0.23 to 2.42). The study was small and not powered to evaluate the impact of budesonide on clinical remission. Suppression of plasma cortisol was significantly more common in prednisolone treated patients (RR 0.02, 95% CI 0.0 to 0.33). Two multicenter studies are ongoing.
Authors' conclusions: At present, there is no evidence to recommend the clinical use of oral budesonide for the induction of remission in active ulcerative colitis. Mesalamine is superior to budesonide for the treatment of active ulcerative colitis.