Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study

Simon P L Travis, Silvio Danese, Limas Kupcinskas, Olga Alexeeva, Geert D'Haens, Peter R Gibson, Luigi Moro, Richard Jones, E David Ballard, Johan Masure, Matteo Rossini, William J Sandborn, Simon P L Travis, Silvio Danese, Limas Kupcinskas, Olga Alexeeva, Geert D'Haens, Peter R Gibson, Luigi Moro, Richard Jones, E David Ballard, Johan Masure, Matteo Rossini, William J Sandborn

Abstract

Objective: Budesonide MMX is a novel oral formulation of budesonide that uses Multi-Matrix System (MMX) technology to extend release to the colon. This study compared the efficacy of budesonide MMX with placebo in patients with active, mild-to-moderate ulcerative colitis (UC).

Design: Patients were randomised 1:1:1:1 to receive budesonide MMX 9 mg or 6 mg, or Entocort EC 9 mg (budesonide controlled ileal-release capsules; reference arm) or placebo once daily for 8 weeks. The primary endpoint was combined clinical and endoscopic remission, defined as UC Disease Activity Index score ≤1 with a score of 0 for rectal bleeding and stool frequency, no mucosal friability on colonoscopy, and a ≥1-point reduction in endoscopic index score from baseline.

Results: 410 patients were evaluated for efficacy. Combined clinical and endoscopic remission rates with budesonide MMX 9 mg or 6 mg, Entocort EC and placebo were 17.4%, 8.3%, 12.6% and 4.5%, respectively. The difference between budesonide MMX 9 mg and placebo was significant (OR 4.49; 95% CI 1.47 to 13.72; p=0.0047). Budesonide MMX 9 mg was associated with numerically higher rates of clinical (42.2% vs 33.7%) and endoscopic improvement (42.2% vs 31.5%) versus placebo. The rate of histological healing (16.5% vs 6.7%; p=0.0361) and proportion of patients with symptom resolution (23.9% vs 11.2%; p=0.0220) were significantly higher for budesonide MMX 9 mg than placebo. Adverse event profiles were similar across groups.

Conclusion: Budesonide MMX 9 mg was safe and more effective than placebo at inducing combined clinical and endoscopic remission in patients with active, mild-to-moderate UC.

Trial registration: ClinicalTrials.gov NCT00679380.

Keywords: IBD; Inflammatory Bowel Disease; Ulcerative Colitis.

Figures

Figure 1
Figure 1
Patient flow and disposition. AE, adverse event; Bud, budesonide; GCP, Good Clinical Practice; mITT, modified intention to treat; QD, daily.
Figure 2
Figure 2
Primary endpoint: combined clinical and endoscopic remission at week 8 (modified intention-to-treat population; n=410). Statistically significant versus placebo at the *α=0.025 (p=0.0047) or †α=0.05 (p=0.0481) level. Not powered to show statistical difference between budesonide Multi-Matrix System (MMX) treatment arms and Entocort EC.
Figure 3
Figure 3
OR analysis of budesonide Multi-Matrix System 9 mg versus placebo.

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