Budesonide for Maintenance of Remission in Crohnʼs Disease: Update of a Systematic Review and Meta-analysis for the Cochrane Collaboration

Abstract

Purpose: Budesonide (BUD) has been shown to be effective for induction of remission in Crohn's disease (CD), but concerns have been raised about the efficacy and safety of its long-term use. This systematic review and meta-analysis examined the efficacy and safety of BUD for maintenance of remission in CD. Methods: MEDLINE, EMBASE, other electronic databases, article reference lists, and conference proceedings were searched up to January, 2013 to identify randomized controlled trials on BUD. Those comparing BUD to a control treatment or comparing two doses of BUD were included. The primary outcome was maintenance of remission at one year. Secondary outcomes included mean change in CD activity index (CDAI), adverse events, and study withdrawal. Two independent investigators reviewed studies for eligibility and extracted the data. For the meta-analysis, a random or fixed effects model was chosen based on an assessment of heterogeneity. Results: Twelve studies were identified. Only one additional study was found since the previous review, which compared azathioprine with BUD. BUD 6 mg daily was no more effective than placebo for maintenance of remission at 3 months (RR 1.25, 95% CI 1.00-1.58), 6 months (RR 1.15, 95% CI 0.95-1.39), or 12 months (RR 1.13, 95% CI 0.94-1.35). BUD was neither more effective than azathioprine (RR 0.81, 95% CI 0.61-1.08), nor weaning doses of prednisolone for maintenance of remission at 12 months (RR 0.79; 95% CI 0.55-1.13), but was better than mesalamine (RR 2.51, 95% CI 1.03-6.12). BUD 3 mg daily was more effective than placebo at 3 months (RR 1.31, 95% CI 1.03-1.67). This benefit was not sustained at 6 months (RR 1.10; 95% CI 0.81-1.50), or 12 months (RR 1.04, 95% CI 0.84-1.30). The use of BUD 6 mg resulted in a modest improvement in CDAI scores at 12 months (WMD -23.49; 95% CI -46.65 to -0.32). Adverse events were more frequent in patients treated with 6 mg of BUD, compared with placebo (RR 1.49; 95% CI 1.01-2.19). Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg daily (RR 2.88; 95% CI 1.72-4.82) and 3 mg daily (RR 2.73, 95% CI 1.34-5.57), compared with placebo. Patients receiving BUD were less likely to withdraw due to adverse events than those receiving azathioprine (RR 0.42; 95% CI 0.18-0.97). Conclusion: BUD is not more effective than placebo for maintenance of remission in CD. BUD results in a modest drop in CDAI scores; however, these benefits are offset by higher adverse events and more frequent adrenocorticoid suppression in patients receiving BUD. Lack of superiority of BUD compared to azathioprine is a new finding in this update. Disclosure - EK, AR, EIB - none. GGK - speaker for Merck, Schering-Plough, Abbott, and UCB Pharma; participated in advisory board meetings for Abbott, Merck, Schering-Plough, Shire, and UCB Pharma; research support from Abbott and Shire. ARO - advisory board for Janssen Canada, Abbvie Canada, Nestle Canada; research support (clinical trial site) from Janssen, Abbvie, Optimer US, Janssen US, Astra-Zeneca AHS - advisory boards for Merck, Abbott, and Shire; Speakers Bureau for Merck, Abbott, Shire, Aptalis, and Warner Chilcott; research support from Merck and Abbott CHS - advisory boards for Janssen Canada, Abbvie; Speaker for Janssen Canada; research support from Janssen Canada.