title: 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.affiliation: Agaplesion Markus Krankenhaus, 1st Dept. of Medicine, Goethe-University, 60431 Frankfurt am Main, Germany. Electronic address: axel.dignass@fdk.info.
authors.forename: Axel
authors.initials: A
authors.lastname: Dignass
authors.affiliation: University General Hospital for Active Treatment "Tzaritza Yoanna", Clinic of Gastroenterology, 1527 Sofia, Bulgaria. Electronic address: simeon_stoinov@abv.bg.
authors.forename: Simeon
authors.initials: S
authors.lastname: Stoynov
authors.affiliation: Donetsk City Clinical Hospital No. 3, Gastroenterology Dept., M. Gorkyy Donetsk National Medical University, Donetsk, 83003 Donetsk, Ukraine. Electronic address: dorofeyev@med.finfort.com.
authors.forename: Andrey E
authors.initials: AE
authors.lastname: Dorofeyev
authors.affiliation: I.M. Sechenov First Moscow Medical State University, Conservative Coloproctology Dept., 119992 Moscow, Russia.
authors.forename: Galina A
authors.initials: GA
authors.lastname: Grigorieva
authors.affiliation: District Hospital Mladá Boleslav, 293 01 Mladá Boleslav II, Czech Republic. Electronic address: evatomsova@seznam.cz.
authors.forename: Eva
authors.initials: E
authors.lastname: Tomsová
authors.affiliation: DEOEC, II. sz. Belgyógyászati Klinika, 4012 Debrecen, Hungary. Electronic address: altorjay@med.unideb.hu.
authors.forename: István
authors.initials: I
authors.lastname: Altorjay
authors.affiliation: Medical Center Tuculanu, 300158 Timisoara, Romania. Electronic address: danieltuculanu@yahoo.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tuculanu
authors.affiliation: Gastro I. s.r.o., Gastroenterology Dept., 080 01 Prešov, Slovakia. Electronic address: bunganic.ivan15@zoznam.sk.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bunganič
authors.affiliation: Paula Stradina University Hospital, Center of Gastroenterology, 1002 Riga, Latvia. Electronic address: pokrot@latnet.lv.
authors.forename: Juris
authors.initials: J
authors.lastname: Pokrotnieks
authors.affiliation: Lithuanian University of Health Sciences, Dept. of Gastroenterology, 50009 Kaunas, Lithuania. Electronic address: likup@takas.lt.
authors.forename: Limas
authors.initials: L
authors.lastname: Kupčinskas
authors.affiliation: Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany. Electronic address: dilger@drfalkpharma.de.
authors.forename: Karin
authors.initials: K
authors.lastname: Dilger
authors.affiliation: Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany. Electronic address: greinwald@drfalkpharma.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Greinwald
authors.affiliation: Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany. Electronic address: mueller@drfalkpharma.de.
authors.forename: Ralph
authors.initials: R
authors.lastname: Mueller
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D019819:Budesonide / Q000008:administration & dosage*; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D019819:Budesonide
keywords: Adherence; Budesonide; Clinical remission; Crohn's disease; Dosing