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

Research output: Article

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

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Budesonide
Crohn Disease
Population
Drug-Related Side Effects and Adverse Reactions
Ulcer
Observation
Safety

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Dignass, A., Stoynov, S., Dorofeyev, A. E., Grigorieva, G. A., Tomsová, E., Altorjay, I., ... 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

Once versus three times daily dosing of oral budesonide for active Crohn's disease : A double-blind, double-dummy, randomised trial. / Dignass, Axel; Stoynov, Simeon; Dorofeyev, Andrey E.; Grigorieva, Galina A.; Tomsová, Eva; Altorjay, István; Tuculanu, Daniel; Bunganič, Ivan; Pokrotnieks, Juris; Kupčinskas, Limas; Dilger, Karin; Greinwald, Roland; Mueller, Ralph; Stoynov, S.; Penchev, P.; Kadian, H.; Kotzev, M.; Stamboliyska, I.; Atanassova, A.; Petrov, A.; Chavushian, A.; Balabanska, R.; Tsonev, R.; Vasileva, G.; Novakov, Y.; Kurktschiev, D.; Temelkova-Kurktschiev, T.; Lukas, M.; Bortlik, M.; Gabalec, L.; Šimon, V.; Jungwirthová, A.; P.Matejková; Širokỳ, M.; Slezák, L.; Tomsová, E.; Marcek, J.; Benko, P.; Golánová, J.; Komárek, V.; Dignass, A.; Böhmig, M.; Schulze, H. A.; Cordes, H. J.; Dienethal, A.; Claudé, R.; Klugmann, T.; Teich, N.; Borkenhagen, A.; Schroeder, M.; Hinrichsen, H.; Tulassay, Z.; Herszényi, L.; Juhász, M.; Miheller, P.; Mihály, E.; Altorjay, I.; Palatka, K.; Kacska, S.; Demeter, P.; Penyige, J.; Sike, R.; Mester, G.; Balogh, M.; Rácz, I.; Szabó, A.; Karasz, T.; Csöndes, M.; Pokrotnieks, J.; Pukitis, A.; Derova, J.; Derovs, A.; Kupcinskas, L.; Jonaitis, L.; Kiudelis, G.; Buineviciute, A.; Radžiunas, G.; Cristea, V.; Burz, C. C.; Muti, D.; Dina, I.; Iacobescu, C.; Fratila, O.; Ilias, T.; Gheorghe, L.; Smira, G.; Vadan, R.; Goldis, A.; Bob, F.; Goldis, R.; Kallikkot, S.; Tuculanu, D.; Paunescu, M. G.; Covasintan, S.; Belousova, E. A.; Domareva, I. V.; Grigorieva, G. A.; Meshalkina, N. Y.; Golysheva, S. V.; Grinevich, V. B.; Gubonina, I. V.; Pershko, A. M.; Mikhailova, T. L.; Golovenko, O. V.; Mayat, L. A.; Makarchuk, P. A.; Simanenkov, V. I.; Zakharova, N. V.; Belov, G. N.; Sishkova, E. A.; Tinyakova, T. V.; Raspereza, D. V.; Tkachenko, E. I.; Avalueva, E. B.; Zhigalova, T. N.; Skazyvaeva, E.; Mirgorodskaya, E.; Yakovenko, E. P.; Agafonova, N. A.; Ivanov, A. N.; Yakovenko, A. V.; Pryanishnikova, A. S.; Abdulganiyeva, D. I.; Odintsova, A. H.; Bodryagina, E. S.; Glebasheva, S. G.; Alekseeva, O. P.; Krishtopenko, S. V.; Dolgikh, O. Y.; Andreev, P. P.; Lukashova, A. V.; Pavlenko, V. V.; Aleksandrovna, S. B.; Kataganova, G. A.; Korablina, N. V.; Starostin, B. D.; Starostina, G.; Tkachev, A. V.; Nikitina, K. E.; Mkrtchyan, L. S.; Yakovlev, A. A.; Stolyarova, I. G.; Volkov, A. S.; Krishchenko, V.; Valuiskikh, E. Y.; Gilinskaya, O. M.; Miroshnichenko, E.; Barickỳ, B.; Bunganic, I.; Pekárková, B.; Pekárek, B.; Golovchenko, O. I.; Nosova, I. A.; Zaporozhets, O. N.; Dorofeyev, A. E.; Rassokhina, O. A.; Lozynskyy, Y. S.; Leoshyk, O. V.; Seplyvyy, I. V.; Zakharash, M. P.; Zakharash, Y. M.; Kravchenko, T. G.

In: Journal of Crohn's and Colitis, Vol. 8, No. 9, 01.09.2014, p. 970-980.

Research output: Article

Dignass, A, Stoynov, S, Dorofeyev, AE, Grigorieva, GA, 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, Petrov, A, Chavushian, A, Balabanska, R, Tsonev, R, Vasileva, G, Novakov, Y, Kurktschiev, D, Temelkova-Kurktschiev, T, Lukas, M, Bortlik, M, Gabalec, L, Šimon, V, Jungwirthová, A, P.Matejková, Širokỳ, M, Slezák, L, Tomsová, E, Marcek, J, Benko, P, Golánová, J, Komárek, V, Dignass, A, Böhmig, M, Schulze, HA, Cordes, HJ, Dienethal, A, Claudé, R, Klugmann, T, Teich, N, Borkenhagen, A, Schroeder, M, Hinrichsen, H, Tulassay, Z, Herszényi, L, Juhász, M, Miheller, P, Mihály, E, Altorjay, I, Palatka, K, Kacska, S, Demeter, P, Penyige, J, Sike, R, Mester, G, Balogh, M, Rácz, I, Szabó, A, Karasz, T, Csöndes, M, Pokrotnieks, J, Pukitis, A, Derova, J, Derovs, A, Kupcinskas, L, Jonaitis, L, Kiudelis, G, Buineviciute, A, Radžiunas, G, Cristea, V, Burz, CC, Muti, D, Dina, I, Iacobescu, C, Fratila, O, Ilias, T, Gheorghe, L, Smira, G, Vadan, R, Goldis, A, Bob, F, Goldis, R, Kallikkot, S, Tuculanu, D, Paunescu, MG, Covasintan, S, Belousova, EA, Domareva, IV, Grigorieva, GA, Meshalkina, NY, Golysheva, SV, Grinevich, VB, Gubonina, IV, Pershko, AM, Mikhailova, TL, Golovenko, OV, Mayat, LA, Makarchuk, PA, Simanenkov, VI, Zakharova, NV, Belov, GN, Sishkova, EA, Tinyakova, TV, Raspereza, DV, Tkachenko, EI, Avalueva, EB, Zhigalova, TN, Skazyvaeva, E, Mirgorodskaya, E, Yakovenko, EP, Agafonova, NA, Ivanov, AN, Yakovenko, AV, Pryanishnikova, AS, Abdulganiyeva, DI, Odintsova, AH, Bodryagina, ES, Glebasheva, SG, Alekseeva, OP, Krishtopenko, SV, Dolgikh, OY, Andreev, PP, Lukashova, AV, Pavlenko, VV, Aleksandrovna, SB, Kataganova, GA, Korablina, NV, Starostin, BD, Starostina, G, Tkachev, AV, Nikitina, KE, Mkrtchyan, LS, Yakovlev, AA, Stolyarova, IG, Volkov, AS, Krishchenko, V, Valuiskikh, EY, Gilinskaya, OM, Miroshnichenko, E, Barickỳ, B, Bunganic, I, Pekárková, B, Pekárek, B, Golovchenko, OI, Nosova, IA, Zaporozhets, ON, Dorofeyev, AE, Rassokhina, OA, Lozynskyy, YS, Leoshyk, OV, Seplyvyy, IV, Zakharash, MP, Zakharash, YM & Kravchenko, TG 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, vol. 8, no. 9, pp. 970-980. https://doi.org/10.1016/j.crohns.2014.01.021
Dignass, Axel ; Stoynov, Simeon ; Dorofeyev, Andrey E. ; Grigorieva, Galina A. ; Tomsová, Eva ; Altorjay, István ; Tuculanu, Daniel ; Bunganič, Ivan ; Pokrotnieks, Juris ; Kupčinskas, Limas ; Dilger, Karin ; Greinwald, Roland ; Mueller, Ralph ; Stoynov, S. ; Penchev, P. ; Kadian, H. ; Kotzev, M. ; Stamboliyska, I. ; Atanassova, A. ; Petrov, A. ; Chavushian, A. ; Balabanska, R. ; Tsonev, R. ; Vasileva, G. ; Novakov, Y. ; Kurktschiev, D. ; Temelkova-Kurktschiev, T. ; Lukas, M. ; Bortlik, M. ; Gabalec, L. ; Šimon, V. ; Jungwirthová, A. ; P.Matejková ; Širokỳ, M. ; Slezák, L. ; Tomsová, E. ; Marcek, J. ; Benko, P. ; Golánová, J. ; Komárek, V. ; Dignass, A. ; Böhmig, M. ; Schulze, H. A. ; Cordes, H. J. ; Dienethal, A. ; Claudé, R. ; Klugmann, T. ; Teich, N. ; Borkenhagen, A. ; Schroeder, M. ; Hinrichsen, H. ; Tulassay, Z. ; Herszényi, L. ; Juhász, M. ; Miheller, P. ; Mihály, E. ; Altorjay, I. ; Palatka, K. ; Kacska, S. ; Demeter, P. ; Penyige, J. ; Sike, R. ; Mester, G. ; Balogh, M. ; Rácz, I. ; Szabó, A. ; Karasz, T. ; Csöndes, M. ; Pokrotnieks, J. ; Pukitis, A. ; Derova, J. ; Derovs, A. ; Kupcinskas, L. ; Jonaitis, L. ; Kiudelis, G. ; Buineviciute, A. ; Radžiunas, G. ; Cristea, V. ; Burz, C. C. ; Muti, D. ; Dina, I. ; Iacobescu, C. ; Fratila, O. ; Ilias, T. ; Gheorghe, L. ; Smira, G. ; Vadan, R. ; Goldis, A. ; Bob, F. ; Goldis, R. ; Kallikkot, S. ; Tuculanu, D. ; Paunescu, M. G. ; Covasintan, S. ; Belousova, E. A. ; Domareva, I. V. ; Grigorieva, G. A. ; Meshalkina, N. Y. ; Golysheva, S. V. ; Grinevich, V. B. ; Gubonina, I. V. ; Pershko, A. M. ; Mikhailova, T. L. ; Golovenko, O. V. ; Mayat, L. A. ; Makarchuk, P. A. ; Simanenkov, V. I. ; Zakharova, N. V. ; Belov, G. N. ; Sishkova, E. A. ; Tinyakova, T. V. ; Raspereza, D. V. ; Tkachenko, E. I. ; Avalueva, E. B. ; Zhigalova, T. N. ; Skazyvaeva, E. ; Mirgorodskaya, E. ; Yakovenko, E. P. ; Agafonova, N. A. ; Ivanov, A. N. ; Yakovenko, A. V. ; Pryanishnikova, A. S. ; Abdulganiyeva, D. I. ; Odintsova, A. H. ; Bodryagina, E. S. ; Glebasheva, S. G. ; Alekseeva, O. P. ; Krishtopenko, S. V. ; Dolgikh, O. Y. ; Andreev, P. P. ; Lukashova, A. V. ; Pavlenko, V. V. ; Aleksandrovna, S. B. ; Kataganova, G. A. ; Korablina, N. V. ; Starostin, B. D. ; Starostina, G. ; Tkachev, A. V. ; Nikitina, K. E. ; Mkrtchyan, L. S. ; Yakovlev, A. A. ; Stolyarova, I. G. ; Volkov, A. S. ; Krishchenko, V. ; Valuiskikh, E. Y. ; Gilinskaya, O. M. ; Miroshnichenko, E. ; Barickỳ, B. ; Bunganic, I. ; Pekárková, B. ; Pekárek, B. ; Golovchenko, O. I. ; Nosova, I. A. ; Zaporozhets, O. N. ; Dorofeyev, A. E. ; Rassokhina, O. A. ; Lozynskyy, Y. S. ; Leoshyk, O. V. ; Seplyvyy, I. V. ; Zakharash, M. P. ; Zakharash, Y. M. ; Kravchenko, T. G. / Once versus three times daily dosing of oral budesonide for active Crohn's disease : A double-blind, double-dummy, randomised trial. In: Journal of Crohn's and Colitis. 2014 ; Vol. 8, No. 9. pp. 970-980.
@article{26fb391fd74948cf85167b1e6e9db4d4,
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 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.",
keywords = "Adherence, Budesonide, Clinical remission, Crohn's disease, Dosing",
author = "Axel Dignass and Simeon Stoynov and Dorofeyev, {Andrey E.} and Grigorieva, {Galina A.} and Eva Tomsov{\'a} and Istv{\'a}n Altorjay and Daniel Tuculanu and Ivan Bunganič and Juris Pokrotnieks and Limas Kupčinskas and Karin Dilger and Roland Greinwald and Ralph Mueller and S. Stoynov and P. Penchev and H. Kadian and M. Kotzev and I. Stamboliyska and A. Atanassova and A. Petrov and A. Chavushian and R. Balabanska and R. Tsonev and G. Vasileva and Y. Novakov and D. Kurktschiev and T. Temelkova-Kurktschiev and M. Lukas and M. Bortlik and L. Gabalec and V. Šimon and A. Jungwirthov{\'a} and P.Matejkov{\'a} and M. Širokỳ and L. Slez{\'a}k and E. Tomsov{\'a} and J. Marcek and P. Benko and J. Gol{\'a}nov{\'a} and V. Kom{\'a}rek and A. Dignass and M. B{\"o}hmig and Schulze, {H. A.} and Cordes, {H. J.} and A. Dienethal and R. Claud{\'e} and T. Klugmann and N. Teich and A. Borkenhagen and M. Schroeder and H. Hinrichsen and Z. Tulassay and L. Hersz{\'e}nyi and M. Juh{\'a}sz and P. Miheller and E. Mih{\'a}ly and I. Altorjay and K. Palatka and S. Kacska and P. Demeter and J. Penyige and R. Sike and G. Mester and M. Balogh and I. R{\'a}cz and A. Szab{\'o} and T. Karasz and M. Cs{\"o}ndes and J. Pokrotnieks and A. Pukitis and J. Derova and A. Derovs and L. Kupcinskas and L. Jonaitis and G. Kiudelis and A. Buineviciute and G. Radžiunas and V. Cristea and Burz, {C. C.} and D. Muti and I. Dina and C. Iacobescu and O. Fratila and T. Ilias and L. Gheorghe and G. Smira and R. Vadan and A. Goldis and F. Bob and R. Goldis and S. Kallikkot and D. Tuculanu and Paunescu, {M. G.} and S. Covasintan and Belousova, {E. A.} and Domareva, {I. V.} and Grigorieva, {G. A.} and Meshalkina, {N. Y.} and Golysheva, {S. V.} and Grinevich, {V. B.} and Gubonina, {I. V.} and Pershko, {A. M.} and Mikhailova, {T. L.} and Golovenko, {O. V.} and Mayat, {L. A.} and Makarchuk, {P. A.} and Simanenkov, {V. I.} and Zakharova, {N. V.} and Belov, {G. N.} and Sishkova, {E. A.} and Tinyakova, {T. V.} and Raspereza, {D. V.} and Tkachenko, {E. I.} and Avalueva, {E. B.} and Zhigalova, {T. N.} and E. Skazyvaeva and E. Mirgorodskaya and Yakovenko, {E. P.} and Agafonova, {N. A.} and Ivanov, {A. N.} and Yakovenko, {A. V.} and Pryanishnikova, {A. S.} and Abdulganiyeva, {D. I.} and Odintsova, {A. H.} and Bodryagina, {E. S.} and Glebasheva, {S. G.} and Alekseeva, {O. P.} and Krishtopenko, {S. V.} and Dolgikh, {O. Y.} and Andreev, {P. P.} and Lukashova, {A. V.} and Pavlenko, {V. V.} and Aleksandrovna, {S. B.} and Kataganova, {G. A.} and Korablina, {N. V.} and Starostin, {B. D.} and G. Starostina and Tkachev, {A. V.} and Nikitina, {K. E.} and Mkrtchyan, {L. S.} and Yakovlev, {A. A.} and Stolyarova, {I. G.} and Volkov, {A. S.} and V. Krishchenko and Valuiskikh, {E. Y.} and Gilinskaya, {O. M.} and E. Miroshnichenko and B. Barickỳ and I. Bunganic and B. Pek{\'a}rkov{\'a} and B. Pek{\'a}rek and Golovchenko, {O. I.} and Nosova, {I. A.} and Zaporozhets, {O. N.} and Dorofeyev, {A. E.} and Rassokhina, {O. A.} and Lozynskyy, {Y. S.} and Leoshyk, {O. V.} and Seplyvyy, {I. V.} and Zakharash, {M. P.} and Zakharash, {Y. M.} and Kravchenko, {T. G.}",
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doi = "10.1016/j.crohns.2014.01.021",
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volume = "8",
pages = "970--980",
journal = "Journal of Crohn's and Colitis",
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}

TY - JOUR

T1 - Once versus three times daily dosing of oral budesonide for active Crohn's disease

T2 - A double-blind, double-dummy, randomised trial

AU - Dignass, Axel

AU - Stoynov, Simeon

AU - Dorofeyev, Andrey E.

AU - Grigorieva, Galina A.

AU - Tomsová, Eva

AU - Altorjay, István

AU - Tuculanu, Daniel

AU - Bunganič, Ivan

AU - Pokrotnieks, Juris

AU - Kupčinskas, Limas

AU - Dilger, Karin

AU - Greinwald, Roland

AU - Mueller, Ralph

AU - Stoynov, S.

AU - Penchev, P.

AU - Kadian, H.

AU - Kotzev, M.

AU - Stamboliyska, I.

AU - Atanassova, A.

AU - Petrov, A.

AU - Chavushian, A.

AU - Balabanska, R.

AU - Tsonev, R.

AU - Vasileva, G.

AU - Novakov, Y.

AU - Kurktschiev, D.

AU - Temelkova-Kurktschiev, T.

AU - Lukas, M.

AU - Bortlik, M.

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PY - 2014/9/1

Y1 - 2014/9/1

N2 - 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.

AB - 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.

KW - Adherence

KW - Budesonide

KW - Clinical remission

KW - Crohn's disease

KW - Dosing

UR - http://www.scopus.com/inward/record.url?scp=84906792062&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906792062&partnerID=8YFLogxK

U2 - 10.1016/j.crohns.2014.01.021

DO - 10.1016/j.crohns.2014.01.021

M3 - Article

C2 - 24534142

AN - SCOPUS:84906792062

VL - 8

SP - 970

EP - 980

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 9

ER -