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

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, S. Stoynov, P. Penchev, H. Kadian, M. Kotzev, I. Stamboliyska, A. Atanassova, A. PetrovA. Chavushian, R. Balabanska, R. Tsonev, G. Vasileva, Y. Novakov, D. Kurktschiev, T. Temelkova-Kurktschiev, M. Lukas, M. Bortlik, L. Gabalec, V. Šimon, A. Jungwirthová, P.Matejková, M. Širokỳ, L. Slezák, E. Tomsová, J. Marcek, P. Benko, J. Golánová, V. Komárek, A. Dignass, M. Böhmig, H. A. Schulze, H. J. Cordes, A. Dienethal, R. Claudé, T. Klugmann, N. Teich, A. Borkenhagen, M. Schroeder, H. Hinrichsen, Z. Tulassay, L. Herszényi, M. Juhász, P. Miheller, E. Mihály, I. Altorjay, K. Palatka, S. Kacska, P. Demeter, J. Penyige, R. Sike, G. Mester, M. Balogh, I. Rácz, A. Szabó, T. Karasz, M. Csöndes, J. Pokrotnieks, A. Pukitis, J. Derova, A. Derovs, L. Kupcinskas, L. Jonaitis, G. Kiudelis, A. Buineviciute, G. Radžiunas, V. Cristea, C. C. Burz, D. Muti, I. Dina, C. Iacobescu, O. Fratila, T. Ilias, L. Gheorghe, G. Smira, R. Vadan, A. Goldis, F. Bob, R. Goldis, S. Kallikkot, D. Tuculanu, M. G. Paunescu, S. Covasintan, E. A. Belousova, I. V. Domareva, G. A. Grigorieva, N. Y. Meshalkina, S. V. Golysheva, V. B. Grinevich, I. V. Gubonina, A. M. Pershko, T. L. Mikhailova, O. V. Golovenko, L. A. Mayat, P. A. Makarchuk, V. I. Simanenkov, N. V. Zakharova, G. N. Belov, E. A. Sishkova, T. V. Tinyakova, D. V. Raspereza, E. I. Tkachenko, E. B. Avalueva, T. N. Zhigalova, E. Skazyvaeva, E. Mirgorodskaya, E. P. Yakovenko, N. A. Agafonova, A. N. Ivanov, A. V. Yakovenko, A. S. Pryanishnikova, D. I. Abdulganiyeva, A. H. Odintsova, E. S. Bodryagina, S. G. Glebasheva, O. P. Alekseeva, S. V. Krishtopenko, O. Y. Dolgikh, P. P. Andreev, A. V. Lukashova, V. V. Pavlenko, S. B. Aleksandrovna, G. A. Kataganova, N. V. Korablina, B. D. Starostin, G. Starostina, A. V. Tkachev, K. E. Nikitina, L. S. Mkrtchyan, A. A. Yakovlev, I. G. Stolyarova, A. S. Volkov, V. Krishchenko, E. Y. Valuiskikh, O. M. Gilinskaya, E. Miroshnichenko, B. Barickỳ, I. Bunganic, B. Pekárková, B. Pekárek, O. I. Golovchenko, I. A. Nosova, O. N. Zaporozhets, A. E. Dorofeyev, O. A. Rassokhina, Y. S. Lozynskyy, O. V. Leoshyk, I. V. Seplyvyy, M. P. Zakharash, Y. M. Zakharash, T. G. Kravchenko

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20 Citations (Scopus)

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 3. mg 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 [3 mg 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 3 mg 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 3 mg TID dosing in mild-to-moderately active Crohn's disease.

Original languageEnglish
Pages (from-to)970-980
Number of pages11
JournalJournal of Crohn's and Colitis
Volume8
Issue number9
DOIs
Publication statusPublished - szept. 1 2014

ASJC Scopus subject areas

  • Gastroenterology

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    Dignass, A., Stoynov, S., Dorofeyev, A. E., Grigorieva, G. A., Tomsová, E., Altorjay, I., Tuculanu, D., Bunganič, I., Pokrotnieks, J., Kupčinskas, L., Dilger, K., Greinwald, R., Mueller, R., Stoynov, S., Penchev, P., Kadian, H., Kotzev, M., Stamboliyska, I., Atanassova, A., ... Kravchenko, T. G. (2014). Once versus three times daily dosing of oral budesonide for active Crohn's disease: A double-blind, double-dummy, randomised trial. Journal of Crohn's and Colitis, 8(9), 970-980. https://doi.org/10.1016/j.crohns.2014.01.021