Abstract
Background and aims:Cumulative safety and tolerability of budesonide MMX, a once-daily oral corticosteroid for inducing mild to moderate ulcerative colitis remission, was examined.Methods:Data from three randomized, double-blind, placebo-controlled, phase II or III studies [budesonide MMX 9mg, 6mg, or 3mg for 8 weeks]; one phase II study [randomisation to budesonide MMX 9mg or placebo for 4 weeks, then open-label budesonide MMX 9mg for 4 weeks]; and one open-label study [budesonide MMX 9mg for 8 weeks] were pooled.Results:Patients randomised to budesonide MMX 9mg [n = 288], 6mg [n = 254], or placebo [n = 293] had similar rates of adverse events [AEs] [27.1%, 24.8%, and 23.9%, respectively] and serious AEs [2.4%, 2.0%, and 2.7%, respectively]; treatment-related AEs and serious AEs were reported by 11.8% and 13.5%, and 5.9% and 2.2%, respectively, of patients receiving budesonide MMX 3mg [n = 17] or open-label budesonide MMX 9mg [n = 89]. Mean morning plasma cortisol concentrations were normal from baseline to final visit across randomised groups; in patients receiving open-label budesonide, mean cortisol concentration was 129.9 nmol/l after 4 weeks, returning to normal concentrations at final visit. Budesonide MMX was not associated with an overall increased risk for glucocorticoid-related adverse effects.Conclusions:Budesonide MMX 9mg was associated with normal mean cortisol concentrations at final visit and an AE incidence comparable to placebo. Overall, budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis.
Highlights
The prevalence of ulcerative colitis [UC] has been noted to be up to 0.51% of the population in Europe, 0.17% in Asia and the MiddleEast, and up to 0.25% in North America.[1]
Given the potential safety concerns associated with the use of corticosteroids, the objective of the current analysis was to conduct a safety and tolerability assessment of budesonide MMX for the induction of remission in patients with mild to moderate UC, by pooling data from five clinical studies
Patients and study design The safety data from five clinical trials were pooled for analysis: two phase III, randomised, double-blind, placebo-controlled studies (CORE I [NCT00679432] and CORE II [NCT00679380]),[12,13] two phase II, randomised, double-blind, placebo-controlled studies [CB-01-02/05 and CRO-03-53], and one phase III open-label study [CB-01-02/06; NCT01100112]
Summary
The prevalence of ulcerative colitis [UC] has been noted to be up to 0.51% of the population in Europe, 0.17% in Asia and the MiddleEast, and up to 0.25% in North America.[1]. The potent, second-generation corticosteroid budesonide may have an improved safety profile over conventional corticosteroids because of its low [10–15%] systemic bioavailability, attributable to its extensive presystemic elimination in the gastrointestinal tract and liver.[7] The affinity of budesonide for the glucocorticoid receptor is approximately 8.5 times higher than that of dexamethasone[8] and 15 times higher than that of prednisolone.[9] Because of its rapid elimination, a form of extended-release budesonide with delayed elimination was developed that uses multi-matrix [MMX®] technology [budesonide MMX].10,11 In this formulation, the active drug is embedded in an inner lipophilic [stearic acid] matrix with an overlying amphiphilic [lecithin] matrix and surrounded by a hydrophilic [hydroxypropylcellulose] matrix-forming polymer. Budesonide MMX was safe and well tolerated for inducing remission of patients with mild to moderate ulcerative colitis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
