Comparative safety of systemic and low-bioavailability steroids in inflammatory bowel disease: Systematic review and network meta-analysis

AimsOral systemic corticosteroids have been used to induce remission in patients with active inflammatory bowel disease (IBD) for over 50years; however, the wide array of adverse events (AEs) associated with these drugs prompted the development of steroid compounds with targeted delivery and low systemic bioavailability. This study assessed corticosteroids' comparative harm using network meta-analysis. MethodsWe searched PubMed, Scopus, Embase, the Cochrane Library, clinical trial registries, regulatory authorities' websites and major conference proceedings, through March 2017. Randomized controlled trials that recruited adult IBD patients and compared oral systemic corticosteroids (prednisone/prednisolone) or compounds/formulations with low systemic bioavailability (budesonide, budesonide MMX, and beclomethasone dipropionate) with placebo, or against each other, were considered eligible for inclusion. Two reviewers independently extracted study data and outcomes, and rated each trial's risk-of-bias. ResultsWe identified and synthesized evidence from 31 trials including 5689 IBD patients. Budesonide MMX was associated with significantly fewer corticosteroid-related AEs than oral systemic corticosteroids [odds ratio (OR): 0.25, 95% confidence interval (CI): 0.13-0.49] and beclomethasone (OR: 0.35, 95% CI: 0.13-1.00), but not significantly fewer AEs than budesonide (OR: 0.64, 95% CI: 0.37-1.11); it performed equally good with placebo. By contrast, the occurrence of serious AEs, and treatment discontinuations due to AEs, did not differ between the comparator treatments. ConclusionsBudesonide MMX is associated with fewer corticosteroid-related AEs than its comparator steroid treatments for adult IBD patients. Further high-quality research is warranted to illuminate the steroid drugs' comparative safety profiles.