Axel Dignass1, Simeon Stoynov2, Andrey E Dorofeyev3, Galina A Grigorieva4, Eva Tomsová5, István Altorjay6, Daniel Tuculanu7, Ivan Bunganič8, Juris Pokrotnieks9, Limas Kupčinskas10, Karin Dilger11, Roland Greinwald12, Ralph Mueller13. 1. Agaplesion Markus Krankenhaus, 1st Dept. of Medicine, Goethe-University, 60431 Frankfurt am Main, Germany. Electronic address: axel.dignass@fdk.info. 2. University General Hospital for Active Treatment "Tzaritza Yoanna", Clinic of Gastroenterology, 1527 Sofia, Bulgaria. Electronic address: simeon_stoinov@abv.bg. 3. Donetsk City Clinical Hospital No. 3, Gastroenterology Dept., M. Gorkyy Donetsk National Medical University, Donetsk, 83003 Donetsk, Ukraine. Electronic address: dorofeyev@med.finfort.com. 4. I.M. Sechenov First Moscow Medical State University, Conservative Coloproctology Dept., 119992 Moscow, Russia. 5. District Hospital Mladá Boleslav, 293 01 Mladá Boleslav II, Czech Republic. Electronic address: evatomsova@seznam.cz. 6. DEOEC, II. sz. Belgyógyászati Klinika, 4012 Debrecen, Hungary. Electronic address: altorjay@med.unideb.hu. 7. Medical Center Tuculanu, 300158 Timisoara, Romania. Electronic address: danieltuculanu@yahoo.com. 8. Gastro I. s.r.o., Gastroenterology Dept., 080 01 Prešov, Slovakia. Electronic address: bunganic.ivan15@zoznam.sk. 9. Paula Stradina University Hospital, Center of Gastroenterology, 1002 Riga, Latvia. Electronic address: pokrot@latnet.lv. 10. Lithuanian University of Health Sciences, Dept. of Gastroenterology, 50009 Kaunas, Lithuania. Electronic address: likup@takas.lt. 11. Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany. Electronic address: dilger@drfalkpharma.de. 12. Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany. Electronic address: greinwald@drfalkpharma.de. 13. Dr. Falk Pharma GmbH, Clinical Research & Development Dept., 79108 Freiburg, Germany. Electronic address: mueller@drfalkpharma.de.
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.
RCT Entities:
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-CDulcer 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.
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