Budesonide-MMx® 9 mg for induction of remission of mild-to-moderate ulcerative colitis (UC): data from a multicenter, randomized, double-blind placebo-controlled study in the Europe, Russia, Israel and Australia

Abstract

Background: Corticosteroids (CS) are effective in inducing remission in active UC; however, side effects are frequent. Budesonide is a CS with high first-pass metabolism and low systemic bioavailability. MMX® technology is designed for targeted colonic delivery of active drugs. Pharmacoscintigraphic studies have shown that budesonide MMX® tablets deliver budesonide throughout the entire colon. Materials and methods: This study compared once daily budesonide MMX® (B-MMX) 9 mg and 6 mg tablets to placebo over an 8-week treatment period. An oral budesonide formulation designed for targeted delivery to the terminal ileum and the right colon (Entocort®EC 3x3mg administered once daily) was used as a reference comparator. The primary endpoint was the induction of remission as defined by a UCDAI score of ≤ 1 after 8 weeks with scores of 0 for rectal bleeding and stool frequency, and a ≥ 1-point reduction from baseline in the endoscopy score with no sign of mucosal friability. The proportion of patients achieving remission in both the 9 mg and 6 mg B-MMX groups after 8 weeks of treatment was compared with placebo. Results: A total of 511 patients were randomized and received at least 1 dose of study drug. In the modified intent to treat (ITT) population, [which excluded 101 patients with normal histology at baseline, GCP violations, randomization outside the IVRS or with major protocol violations], a significantly greater proportion of patients achieved remission in the B-MMX 9 mg group 17.4% compared with placebo 4.5% (p = 0.0047). Statistical significance was not achieved in the B-MMX 6 mg group. Analyses of all randomized patients (including patients excluded from the modified ITT population but set as non-responders) were also statistically significant for the B-MMX 9 mg group 15.0% (19/127) compared with placebo 3.8% (5/130) (p = 0.0022). There were no significant differences between the stu [...].