Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial.

Abstract

BACKGROUND:

Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy.

METHODS:

An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward).

RESULTS:

The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients.

CONCLUSIONS:

Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease.

• Authors: Axel Dignass, Simeon Stoynov, Andrey E Dorofeyev, Galina A Grigorieva, Eva Tomsová, István Altorjay, Daniel Tuculanu, Ivan Bunganič, Juris Pokrotnieks, Limas Kupčinskas, Karin Dilger, Roland Greinwald, Ralph Mueller, International Budenofalk Study Group
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 8 Issue 9 Pg. 970-80 (Sep 2014) ISSN: 1876-4479 [Electronic] England
• PMID: 24534142 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Chemical References

• Glucocorticoids
• Budesonide

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Budesonide (administration & dosage)
• Crohn Disease (drug therapy, pathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Endoscopy, Gastrointestinal
• Female
• Follow-Up Studies
• Glucocorticoids (administration & dosage)
• Humans
• Intestinal Mucosa (pathology)
• Male
• Middle Aged
• Patient Compliance
• Prospective Studies
• Remission Induction
• Treatment Outcome
• Young Adult