Efficacy and Safety of Oral Budesonide in Patients with Active Crohn’s Disease in Japan: A Multicenter, Double-Blind, Randomized, Parallel-Group Phase 3 Study

Background: US and European guidelines recommend budesonide for the treatment of mild-to-moderate active ileocolic Crohn’s disease (CD). However, budesonide has not been approved, and mesalazine is widely used as first-line treatment in Japan. The objective of this study was to evaluate the efficacy and safety of budesonide in patients with mild-to-moderate active CD in Japan. Methods: In this phase 3 noninferiority study (NCT01514240), 112 patients with a baseline Crohn’s Disease Activity Index (CDAI) score of 180– 400 were randomized to budesonide or mesalazine for 8 weeks. Assessments included remission rate (CDAI score ≤ 150) at weeks 2, 4, and 8, change in CDAI score, health-related quality of life (measured using the Inflammatory Bowel Disease Questionnaire [IBDQ]), and tolerability. Results: The remission rate at week 8 was numerically higher in the Received: June 15, 2017 Accepted: October 5, 2017 Published online: November 22, 2017 Toshifumi Hibi, MD, PhD Center for Advanced IBD Research and Treatment Kitasato Institute Hospital, Kitasato University 5-9-1 Shirokane, Minato-ku, Tokyo (Japan) E-Mail thibi @ insti.kitasato-u.ac.jp © 2017 The Author(s) Published by S. Karger AG, Basel www.karger.com/iid Th is article is licensed under the Creative Commons AttributionNonCommercial-NoDerivatives 4.0 International License (CC BYNC-ND) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes as well as any distribution of modifi ed material requires written permission. Yokoyama/Ohta/Motoya/Takazoe/ Yajima/Date/Nii/Nagy/Suzuki/Hibi Inflamm Intest Dis DOI: 10.1159/000484047 2 mation from 2013 showed that approximately 40,000 patients in Japan received registered treatment for CD in that year [2] . The treatment guidelines for CD in Japan describe 5-aminosalicylic acid (mesalazine) as a common first-line treatment for mild-to-moderate disease [3] . US and European guidelines recommend the glucocorticoid budesonide as a treatment for mild-to-moderate active ileocolic CD because it results in a higher rate of remission induction than mesalazine [4, 5] . However, budesonide had not been approved in Japan at the time the Japanese guidelines were published (in 2013) [3] . Budesonide is approved for use in CD in about 40 countries worldwide. In Western populations, it has been shown to be as effective as prednisolone in the treatment of mild-to-moderate CD [6, 7] , and to be more effective than mesalazine in inducing remission [8] . The efficacy of budesonide in Japanese patients with mild-to-moderate active CD was investigated in a phase 2 study; the proportion of individuals achieving remission after 8 weeks was higher in the budesonide groups than in the placebo group (23 and 28% with budesonide 9 mg and 15 mg once daily [q.d.], respectively, vs. 12% with placebo), although the differences between the two budesonide dose groups or between the budesonide and placebo groups were not statistically significant [9] . In Japan, budesonide was approved for induction of remission in patients with mildto-moderate active CD in September 2016. The purpose of this phase 3 study was to evaluate the clinical efficacy, safety, and tolerability of budesonide 9 mg q.d. compared with mesalazine 1 g three times daily (t.i.d.) in patients with mild-to-moderate active CD in Japan by assessing remission of CD after 8 weeks of treatment. It was hypothesized that the remission rate with budesonide would be noninferior to that with mesalazine.